{ "title": "TAK-653 / osavampator / NBI-1065845 evidence dataset (Condor Research)", "version": "1.4", "cutoff": "2026-10-25", "license": "CC BY 4.0", "creator": "Condor Research Editorial", "url": "https://condorresearch.com/research/tak-653-osavampator-evidence/dataset.json", "data_dictionary": { "census[].evidence_type": "H human data; A animal data (with or without in vitro); V in vitro only; R review or mention; O erratum. Highest applicable level.", "census[].origin": "sponsor = any author affiliated with Takeda, Millennium or Neurocrine, or developer funding; independent otherwise (criterion A).", "census[].data_role": "primary, review_own_data, mention, none.", "trials[]": "ClinicalTrials.gov API v2 fields as retrieved on the cut-off; disp = date the results-delay certification/extension was first posted.", "claims[].verdict": "SUPPORTED, TRIAL_DATA, PARTIAL, CONTRADICTED, NO_SOURCE, NOT_ASSESSABLE (definitions in Table 5 caption).", "human_evidence[]": "One row per human trial; no doses by editorial rule." }, "search_log": { "pubmed": { "query": "\"TAK-653\"[tiab] OR \"TAK653\"[tiab] OR \"TAK 653\"[tiab] OR osavampator[tiab] OR \"NBI-1065845\"[tiab] OR \"NBI1065845\"[tiab] OR \"NBI 1065845\"[tiab] OR \"1358751-06-0\"[tiab] OR \"9E3TOE5RIZ\"[tiab]", "translation": "\"tak 653\"[Title/Abstract] OR \"TAK653\"[Title/Abstract] OR \"tak 653\"[Title/Abstract] OR \"osavampator\"[Title/Abstract] OR \"nbi 1065845\"[Title/Abstract] OR \"NBI1065845\"[Title/Abstract] OR \"nbi 1065845\"[Title/Abstract]", "date": "2026-10-25", "count": 13, "cross_check": "Misma lista (13) con \"TAK-653\" OR \"TAK653\" OR osavampator OR \"NBI-1065845\" OR \"NBI1065845\" OR \"1358751-06-0\" en All Fields; 0 diferencias. SAVITRI[tiab], \"NBI-845\" y el nombre IUPAC dieron 0 registros relevantes." }, "ctgov": { "queries": [ "query.term=TAK-653", "query.term=osavampator", "query.term=NBI-1065845", "query.intr=TAK653", "query.term=NBI-845" ], "date": "2026-10-25", "union": 9, "name_hits": { "TAK-653": [ "NCT02561156", "NCT03312894", "NCT03792672", "NCT05203341", "NCT06786624", "NCT06911112", "NCT06963021", "NCT06966401" ], "osavampator": [ "NCT07196501" ], "NBI-1065845": [ "NCT05203341", "NCT06786624", "NCT06911112", "NCT06963021", "NCT06966401", "NCT07196501" ] } }, "europepmc": "(\"TAK-653\" OR osavampator OR \"NBI-1065845\" OR \"TAK653\") Europe PMC REST, 2026-10-25, hitCount=43 (13 coinciden con PubMed, 1 preprint PPR515505 de PMID 36153330, resto = estos)", "sec_edgar": "efts full-text search 'osavampator' 2025-01-01 to 2026-10-25: 40 hits (Neurocrine, XOMA Royalty, Ligand)", "regulators": [ "openFDA drugsfda (no match)", "EMA medicines report xlsx (no match)", "WADA 2026 List (not named; S0 wording)" ], "forums": [ "https://www.reddit.com/r/NooTopics/comments/vyb4kg/a_guide_to_ampa_positive_allosteric_modulators/", "https://www.reddit.com/r/NooTopics/comments/xojokv/tak653_experiences/", "https://www.reddit.com/r/cognitiveTesting/comments/1jfgc9r/update_tak653_digit_span_improvement/", "https://www.reddit.com/r/antidepressants/comments/1jqrgsj/tak653/", "https://www.reddit.com/r/cognitivescience/comments/1ovf8yj/anyone_tried_acd856_tak653_or_bpn14770_looking/", "https://www.reddit.com/r/Biohackers/comments/1vvtt5f/real_life_limitless_pill_psilocybin_x_tak653/" ] }, "census": [ { "pmid": "31378256", "doi": "10.1016/bs.apha.2019.03.002", "year": 2019, "journal": "Advances in pharmacology (San Diego, Calif.)", "title": "Rapid-acting antidepressants.", "pubmed_pubtypes": [ "Research Support, N.I.H., Extramural", "Research Support, Non-U.S. Gov't", "Review" ], "design": "Revisión narrativa (rapid-acting antidepressants)", "n": null, "registry": null, "first_author": "Witkin JM", "last_author": "Smith JL", "country": "EE. UU.", "developer_affiliated_authors": "0/5", "open_access": "closed", "evidence_type": "R", "origin": "independent", "data_role": "mention" }, { "pmid": "34045439", "doi": "10.1038/s41398-021-01451-2", "year": 2021, "journal": "Translational psychiatry", "title": "Transcranial magnetic stimulation as a translational biomarker for AMPA receptor modulation.", "pubmed_pubtypes": [ "Randomized Controlled Trial", "Research Support, N.I.H., Extramural", "Research Support, Non-U.S. Gov't" ], "design": "Estudio farmacodinámico: rata (TMS/mecanomiografía) + ensayo fase 1 aleatorizado, doble ciego, cruzado, controlado con placebo en voluntarios sanos (TMS motor)", "n": { "rata_pd": 31, "rata_pk": 20, "humanos": 24 }, "registry": "NCT03792672", "first_author": "O'Donnell P", "last_author": "Rosen L", "country": "EE. UU. (Takeda Cambridge MA); ensayo ejecutado en CHDR, Países Bajos", "developer_affiliated_authors": "8/18", "open_access": "gold", "evidence_type": "H", "origin": "sponsor", "data_role": "primary" }, { "pmid": "34267258", "doi": "10.1038/s41598-021-93888-0", "year": 2021, "journal": "Scientific reports", "title": "Strictly regulated agonist-dependent activation of AMPA-R is the key characteristic of TAK-653 for robust synaptic responses and cognitive improvement.", "pubmed_pubtypes": [], "design": "Farmacología preclínica: células CHO recombinantes, neuronas primarias, rodajas cerebrales, conducta en rata, margen frente a convulsión en rata", "n": null, "registry": null, "first_author": "Suzuki A", "last_author": "Kimura H", "country": "Japón", "developer_affiliated_authors": "12/12", "open_access": "gold", "evidence_type": "A", "origin": "sponsor", "data_role": "primary" }, { "pmid": "34290388", "doi": "10.1038/s41598-021-94772-7", "year": 2021, "journal": "Scientific reports", "title": "Author Correction: Strictly regulated agonist-dependent activation of AMPA-R is the key characteristic of TAK-653 for robust synaptic responses and cognitive improvement.", "pubmed_pubtypes": [ "Published Erratum" ], "design": "Corrección de autor (erratum) de PMID 34267258", "n": null, "registry": null, "first_author": "Suzuki A", "last_author": "Kimura H", "country": "Japón", "developer_affiliated_authors": "12/12", "open_access": "gold", "evidence_type": "O", "origin": "sponsor", "data_role": "none" }, { "pmid": "34655652", "doi": "10.1016/j.pbb.2021.173289", "year": 2021, "journal": "Pharmacology, biochemistry, and behavior", "title": "TAK-653, an AMPA receptor potentiator with minimal agonistic activity, produces an antidepressant-like effect with a favorable safety profile in rats.", "pubmed_pubtypes": [ "Research Support, Non-U.S. Gov't" ], "design": "Neuronas corticales primarias de rata (mTOR/BDNF) + modelo conductual de rata (reduction of submissive behavior)", "n": null, "registry": null, "first_author": "Hara H", "last_author": "Kimura H", "country": "Japón", "developer_affiliated_authors": "6/6", "open_access": "hybrid", "evidence_type": "A", "origin": "sponsor", "data_role": "primary" }, { "pmid": "36153330", "doi": "10.1038/s41398-022-02148-w", "year": 2022, "journal": "Translational psychiatry", "title": "Central nervous system effects of TAK-653, an investigational alpha-amino-3-hydroxy-5-methyl-4-isoxazole receptor (AMPAR) positive allosteric modulator in healthy volunteers.", "pubmed_pubtypes": [ "Randomized Controlled Trial", "Research Support, Non-U.S. Gov't" ], "design": "Ensayo fase 1 aleatorizado, doble ciego, controlado con placebo, cruzado de 3 vías, voluntarios sanos (batería NeuroCart)", "n": { "humanos": 24 }, "registry": "NCT03792672", "first_author": "Dijkstra F", "last_author": "Jacobs G", "country": "Países Bajos (CHDR) con coautores Takeda EE. 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Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)", "Part 2: Number of Participants With Treatment-emergent Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS" ], "sponsor": "Neurocrine Biosciences", "why": null }, { "nct": "NCT03312894", "title": "Efficacy and Safety of TAK-653 in Treatment-Resistant Depression", "phase": "2", "status": "Withdrawn", "n": 0, "n_type": "ACTUAL", "start": "2018-02-15", "start_type": "ESTIMATED", "pc": "2019-02-28", "pc_type": "ESTIMATED", "results": false, "results_date": null, "disp": null, "disp_submit": null, "countries": [], "primary": [ "Cohort 1: Time to Relapse of Depressive Symptoms Postdose as Measured by Montgomery Åsberg Depression Rating Scale (MADRS) Total Score" ], "sponsor": "Millennium Pharmaceuticals, Inc.", "why": "Business decision" }, { "nct": "NCT03792672", "title": "A Study to Evaluate Central Nervous System (CNS) Pharmacodynamic Activity of TAK-653 in Healthy Participants Using Transcranial Magnetic Stimulation (TMS)", "phase": "1", "status": "Completed", "n": 24, "n_type": "ACTUAL", "start": "2019-02-11", "start_type": "ACTUAL", "pc": "2019-05-15", "pc_type": "ACTUAL", "results": true, "results_date": "2020-07-02", "disp": null, "disp_submit": null, "countries": [ "Netherlands" ], "primary": [ "Change From Baseline in Peak-to-Peak Amplitude of Motor-evoked Potential (MEP) Obtained With Single-pulse Transcranial Magnetic Stimulation (TMS) for TAK-653 (timing relative to administration omitted)", "Change From Baseline in Resting Motor Threshold (rMT) Obtained With Single-pulse TMS for TAK-653 (timing relative to administration omitted)" ], "sponsor": "Neurocrine Biosciences", "why": null }, { "nct": "NCT05203341", "title": "Study to Assess the Efficacy and Safety of NBI-1065845 in Adults With Major Depressive Disorder (MDD)", "phase": "2", "status": "Completed", "n": 183, "n_type": "ACTUAL", "start": "2022-02-21", "start_type": "ACTUAL", "pc": "2024-01-10", "pc_type": "ACTUAL", "results": false, "results_date": null, "disp": "2024-03-25", "disp_submit": "2025-01-09", "countries": [ "Bulgaria", "Czechia", "Poland", "Slovakia", "Sweden", "United States" ], "primary": [ "Change from Baseline in Total Montgomery Åsberg Depression Rating Scale (MADRS) Score at Day 28" ], "sponsor": "Neurocrine Biosciences", "why": null }, { "nct": "NCT06786624", "title": "Study to Assess the Efficacy and Safety of NBI-1065845 as an Adjunctive Treatment in Participants With Major Depressive Disorder (MDD)", "phase": "3", "status": "Recruiting", "n": 200, "n_type": "ESTIMATED", "start": "2025-01-22", "start_type": "ACTUAL", "pc": "2027-07", "pc_type": "ESTIMATED", "results": false, "results_date": null, "disp": null, "disp_submit": null, "countries": [ "United States" ], "primary": [ "Change from Baseline in Total Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Day 56" ], "sponsor": "Neurocrine Biosciences", "why": null }, { "nct": "NCT06911112", "title": "NBI-1065845-MDD3025: Study to Assess the Efficacy and Safety of NBI-1065845 as an Adjunctive Treatment in Participants With Major Depressive Disorder (MDD)", "phase": "3", "status": "Recruiting", "n": 200, "n_type": "ESTIMATED", "start": "2025-03-31", "start_type": "ACTUAL", "pc": "2027-07", "pc_type": "ESTIMATED", "results": false, "results_date": null, "disp": null, "disp_submit": null, "countries": [ "Bulgaria", "Lithuania", "Romania", "Slovakia", "United States" ], "primary": [ "Change from Baseline in Total Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Day 56" ], "sponsor": "Neurocrine Biosciences", "why": null }, { "nct": "NCT06966401", "title": "Long-Term Study to Assess the Safety and Tolerability of NBI-1065845 as an Adjunctive Treatment in Participants With Major Depressive Disorder (MDD)", "phase": "3", "status": "Recruiting", "n": 850, "n_type": "ESTIMATED", "start": "2025-04-16", "start_type": "ACTUAL", "pc": "2029-05", "pc_type": "ESTIMATED", "results": false, "results_date": null, "disp": null, "disp_submit": null, "countries": [ "Belgium", "Bulgaria", "Canada", "Croatia", "Czechia", "Estonia", "Finland", "Hungary", "Italy", "Latvia", "Lithuania", "Netherlands", "Poland", "Romania", "Slovakia", "Spain", "Sweden", "Taiwan", "United Kingdom", "United States" ], "primary": [ "Number of Participants with Treatment-emergent Adverse Events (TEAEs)" ], "sponsor": "Neurocrine Biosciences", "why": null }, { "nct": "NCT06963021", "title": "NBI-1065845-MDD3026: Study to Assess the Efficacy and Safety of NBI-1065845 as an Adjunctive Treatment in Participants With Major Depressive Disorder (MDD)", "phase": "3", "status": "Recruiting", "n": 200, "n_type": "ESTIMATED", "start": "2025-05-30", "start_type": "ACTUAL", "pc": "2027-07", "pc_type": "ESTIMATED", "results": false, "results_date": null, "disp": null, "disp_submit": null, "countries": [ "Belgium", "Canada", "Finland", "Hungary", "Latvia", "United Kingdom", "United States" ], "primary": [ "Change from Baseline in Total Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Day 56" ], "sponsor": "Neurocrine Biosciences", "why": null }, { "nct": "NCT07196501", "title": "A Study to Evaluate the Maintenance Effect of Osavampator as an Adjunctive Treatment in Participants With Major Depressive Disorder (MDD)", "phase": "3", "status": "Recruiting", "n": 550, "n_type": "ESTIMATED", "start": "2025-08-18", "start_type": "ACTUAL", "pc": "2028-07", "pc_type": "ESTIMATED", "results": false, "results_date": null, "disp": null, "disp_submit": null, "countries": [ "Australia", "Bulgaria", "Canada", "Estonia", "Italy", "Poland", "Serbia", "South Korea", "Spain", "Taiwan", "United States" ], "primary": [ "Time from Randomization to Relapse" ], "sponsor": "Neurocrine Biosciences", "why": null } ], "human_evidence": [ { "trial": "NCT02561156 (first-in-human)", "phase": "1", "years": "2015-2017", "country": "United Kingdom", "n": "88 healthy adults", "design": "Randomised, quadruple-blind, placebo-controlled; 6 single-ascending and 5 multiple-ascending cohorts (repeated administration over 13 days)", "endpoint": "Adverse events, laboratory, vital signs, ECG, EEG, C-SSRS; pharmacokinetics", "result": "No serious adverse events; no clinically significant EEG change; no suicidal ideation or behaviour. Half-life 33 to 48 h, 3- to 4-fold accumulation; CSF/plasma ratio 0.056. Serum BDNF signal inconsistent: a rise at one single-administration level, transient falls at others, not reproduced with repeated administration.", "channel": "Registry results on ClinicalTrials.gov (posted 2019-02-08); conference abstract (ACNP 2018). No journal article.", "funder": "Takeda (record now lists Neurocrine)", "refs": [ "CTSAD", "ACNP2018" ] }, { "trial": "NCT03792672 (TMS / NeuroCart)", "phase": "1", "years": "2019", "country": "Netherlands (CHDR, Leiden)", "n": "24 healthy adults (23 men, 1 woman)", "design": "Randomised, double-blind, placebo-controlled, 3-period crossover with two single-administration levels; then an open-label ketamine period for assay sensitivity", "endpoint": "Motor-evoked potential amplitude and resting motor threshold by TMS (registry primary); NeuroCart battery", "result": "Higher level increased motor-evoked potentials versus placebo (Dunnett-adjusted p = 0.0497); resting motor threshold and paired-pulse measures unchanged. NeuroCart: pattern the authors call 'psychostimulant-like', exploratory, no multiplicity correction. No seizure, dissociation or euphoria adverse events.", "channel": "Two journal articles (2021, 2022); registry results (posted 2020-07-02).", "funder": "Takeda", "refs": [ "34045439", "36153330", "CTTMS" ] }, { "trial": "CYP3A interaction study (no registry number located)", "phase": "1", "years": "before 2024", "country": "United States", "n": "35 healthy adults (18 in the midazolam arm, 17 women in the contraceptive arm)", "design": "Open-label, parallel-arm drug-interaction study", "endpoint": "Geometric mean ratios of midazolam, ethinyl estradiol and levonorgestrel exposure", "result": "For these substrates under these conditions, no CYP3A induction by the authors' criteria. Midazolam and levonorgestrel AUC ratios fell outside the no-effect range without meeting the criteria for an interaction. Somnolence in 9 of 18 in the midazolam arm (a sedative was co-administered); headache in 6 of 17 in the contraceptive arm.", "channel": "One journal article (2024). PubMed tags it 'Randomized Controlled Trial'; the article describes no randomisation.", "funder": "Neurocrine", "refs": [ "38700236" ] }, { "trial": "NCT05203341 / EudraCT 2021-003989-12 (SAVITRI)", "phase": "2", "years": "2021-2024", "country": "United States, Bulgaria, Czechia, Poland, Slovakia, Sweden", "n": "183 adults with MDD and inadequate antidepressant response", "design": "Randomised 2:1:1 (placebo and two dose levels), quadruple-blind, 8 weeks; most participants continued their antidepressant", "endpoint": "Change in MADRS total score at day 28 (primary); day 56, response, remission, CGI-S, PHQ-9 (secondary)", "result": "Two separate comparisons with placebo, no dose-versus-dose comparison reported. Lower dose: day 28 -4.3 points (95% CI -7.8 to -0.8, nominal p = 0.0159); day 56 -7.5 (-12.1 to -2.9). Higher dose: -3.0 (-6.4 to 0.4, p = 0.0873) and -3.6 (-8.0 to 0.8, p = 0.1082). No serious adverse events or deaths.", "channel": "EU Clinical Trials Register results (posted 2025-10-26); press releases (2024-04-23, 2025-09-22); congress abstract and poster (Psych Congress 2025). No journal article; no results on ClinicalTrials.gov.", "funder": "Neurocrine", "refs": [ "EUCTR", "POSTER", "PR2024", "ABSHMP", "CTSAV" ] }, { "trial": "Phase 3 programme (5 trials)", "phase": "3", "years": "2025-2030 (estimated)", "country": "23 countries on ClinicalTrials.gov; 16 EU member states in CTIS", "n": "2,000 estimated across records (not additive: the long-term study may enrol participants from the others)", "design": "Three acute randomised placebo-controlled add-on trials, one randomised-withdrawal maintenance trial, one open-label long-term safety study", "endpoint": "MADRS change at day 56 (acute); time to relapse (maintenance); adverse events (long-term)", "result": "Recruiting; no results. Topline data expected in 2027 according to the company.", "channel": "Registry protocols (ClinicalTrials.gov, CTIS); press releases; SEC filings.", "funder": "Neurocrine", "refs": [ "CTGOV", "CTIS", "10K2025", "PR2026" ] } ], "publication_channels": { "columns": [ "Journal article", "Registry results", "Congress abstract or poster", "Press release", "SEC filing" ], "rows": [ { "trial": "First-in-human (NCT02561156)", "values": [ 0, 1, 1, 0, 0 ] }, { "trial": "TMS / NeuroCart (NCT03792672)", "values": [ 1, 1, 0, 0, 0 ] }, { "trial": "CYP3A interaction (no NCT)", "values": [ 1, 0, 0, 0, 0 ] }, { "trial": "SAVITRI phase 2 (NCT05203341)", "values": [ 0, 1, 1, 1, 1 ] }, { "trial": "Phase 3 programme (5 NCT)", "values": [ 0, 0, 0, 1, 1 ] } ] }, "savitri_sources": { "columns": [ "Item", "ClinicalTrials.gov", "EU Clinical Trials Register (2025-10-26)", "Press release 2024-04-23", "Congress abstract page (2025-10-17)", "Poster PDF (Sept 2025)" ], "rows": [ [ "Primary analysis", "MADRS change at day 28 (protocol)", "Each dose versus placebo, ANCOVA, both labelled pre-specified", "'Study met primary endpoint'; dose not named", "Lower dose significant; p values called nominal", "'Nominal 2-sided significance level of 0.05 (no adjustment for multiplicity)'" ], [ "Day 28, lower dose", "No results posted", "-4.3 (-7.8, -0.8), p = 0.0159", "-4.3, p = 0.0159", "-4.3 (-7.8, -0.8), p = 0.0159", "-4.3 (-7.8, -0.8), p = 0.0159, effect size 0.53" ], [ "Day 28, higher dose", "No results posted", "-3.0 (-6.4, 0.4), p = 0.0873", "-3.0, p = 0.0873", "Not given", "-3.0 (-6.4, 0.4), p = 0.0873" ], [ "Day 56, lower dose", "No results posted", "-7.5 (-12.1, -2.9), p = 0.0016", "-7.5, p = 0.0016", "-6.9 (-11.2, -2.6), p = 0.0018, effect size 0.73", "-7.5 (-12.1, -2.9), p = 0.0016, effect size 0.73" ], [ "Day 56, higher dose", "No results posted", "-3.6 (-8.0, 0.8), p = 0.1082", "-3.6, p = 0.1082", "p = 0.0573", "-3.6 (-8.0, 0.8), p = 0.1082" ], [ "Conduct dates", "Start 2022-02-21; primary completion 2024-01-10", "Recruitment from 2021-12-06; end of trial 2024-02-21", "Not given", "Not given", "2021-12-06 to 2024-02-21" ], [ "Completion", "183 enrolled", "164 completed the study (79, 42, 43)", "183 enrolled", "161 of 183 completed treatment", "161 of 183 completed treatment" ], [ "Results status", "None posted; delayed-results certification listed", "Results v1 posted", "-", "-", "-" ] ], "days_since_primary_completion_without_registry_results": 1019, "certification": { "dispFirstPostDate": "2024-03-25", "dispFirstSubmitDate": "2025-01-09", "note": "API dates are internally inconsistent (submit after post); both reproduced as retrieved." }, "bonferroni_sensitivity": "Our check, not a pre-specified analysis: with alpha split 0.025 per dose, the lower-dose day-28 result (nominal p = 0.0159) stays below threshold; the higher dose is above it at day 28 and day 56. The split covers the two dose comparisons only, not the further time points and secondary endpoints." }, "claims": [ { "n": 1, "claim": "Raises IQ by several points (figures of 6 to 7 points circulate)", "where": "r/NooTopics threads, 2022 and 2024", "verdict": "NO_SOURCE", "evidence": "No registered trial or article measures IQ. Registered human endpoints: safety, pharmacokinetics, TMS motor-evoked potentials, a NeuroCart battery, CYP3A interaction and MADRS.", "refs": [ "CTGOV", "36153330" ] }, { "n": 2, "claim": "Improves working memory and recognition memory", "where": "r/NooTopics, r/cognitiveTesting", "verdict": "PARTIAL", "evidence": "Partial match in rats and 3 monkeys only (developer study): novel object recognition, a radial-arm maze after a drug-induced deficit, and a delayed match-to-sample task at one delay interval. The 24-volunteer NeuroCart study included no memory test.", "refs": [ "34267258", "36153330" ] }, { "n": 3, "claim": "Digit-span scores rise (self-report)", "where": "r/cognitiveTesting, 2025", "verdict": "NO_SOURCE", "evidence": "A single uncontrolled, unblinded self-report. No study of the compound measures digit span.", "refs": [ "CTGOV" ] }, { "n": 4, "claim": "Described on forums as an antidepressant", "where": "r/NooTopics, r/antidepressants", "verdict": "TRIAL_DATA", "evidence": "Trial data exist in adults with major depressive disorder, one sponsor trial (SAVITRI, n = 183): in a separate comparison with placebo, the lower dose arm showed a nominally significant MADRS difference at day 28; the higher dose arm did not. These are trial data from one phase 2 study, not established evidence of benefit. Anhedonia was not a registered endpoint.", "refs": [ "EUCTR", "POSTER", "CTSAV" ] }, { "n": 5, "claim": "It does not cause seizures", "where": "r/Nootropics; vendor pages", "verdict": "PARTIAL", "evidence": "Partial match in rats (convulsion margin 419-fold on Cmax, 1017-fold on AUC) and in short human studies of 24, 35, 88 and 183 participants (no seizure adverse events; no clinically significant EEG change in the 88). People with seizure risk or neurological history were excluded; long-term data are pending.", "refs": [ "34267258", "36153330", "38700236", "CTSAD", "ACNP2018", "POSTER" ] }, { "n": 6, "claim": "No tolerance and no AMPA receptor down-regulation", "where": "r/NooTopics", "verdict": "NO_SOURCE", "evidence": "No human study measures tolerance, receptor regulation or withdrawal. Rat repeated-administration data cover a 3-week behavioural study, without receptor measurements. Reported human half-life 33 to 48 hours with 3- to 4-fold accumulation on repeated administration.", "refs": [ "34655652", "ACNP2018" ] }, { "n": 7, "claim": "It is a stimulant (or, in other threads, that it is not)", "where": "r/NooTopics", "verdict": "PARTIAL", "evidence": "Partial match in 24 healthy volunteers (single administrations): the authors describe a 'psychostimulant-like' NeuroCart profile; subjective drug-effect scales did not change. No abuse-liability study located.", "refs": [ "36153330" ] }, { "n": 8, "claim": "Disturbs sleep (insomnia, vivid dreams)", "where": "r/NooTopics", "verdict": "PARTIAL", "evidence": "Partial match in adults with major depressive disorder (SAVITRI): insomnia reported in 2.2% on placebo and 2.2% and 6.4% in the two active arms. Dreams were not recorded; no sleep study.", "refs": [ "EUCTR", "POSTER" ] }, { "n": 9, "claim": "Claims about combining it with other substances", "where": "r/NooTopics, r/Nootropics", "verdict": "NO_SOURCE", "evidence": "No data on co-administration with any substance named in forums. The only interaction study tested two prescription CYP3A substrates under controlled conditions.", "refs": [ "38700236" ] }, { "n": 10, "claim": "There are no safety data on repeated use", "where": "r/cognitivescience", "verdict": "CONTRADICTED", "evidence": "Contradicted: repeated-administration safety data exist for 13 days in healthy volunteers, 8 weeks in 183 patients and a 35-person interaction study. They are short, and the patient data are not in a journal; the long-term study runs to 2029.", "refs": [ "CTSAD", "EUCTR", "38700236", "CTGOV" ] }, { "n": 11, "claim": "It is a peptide ('TAK peptide')", "where": "vendor SEO pages", "verdict": "CONTRADICTED", "evidence": "Contradicted: C19H23N3O3S, molecular weight 373.5, a small molecule.", "refs": [ "PUBCHEM" ] }, { "n": 12, "claim": "It is one of the best-researched nootropics", "where": "forums", "verdict": "CONTRADICTED", "evidence": "Contradicted: 13 PubMed records, 6 with original data, 5 of them developer-linked; never registered as a cognitive-enhancement trial in humans.", "refs": [ "CENSUS" ] }, { "n": 13, "claim": "Neurocrine has five phase 3 trials running", "where": "r/NooTopics, 2025", "verdict": "SUPPORTED", "evidence": "Five phase 3 records on ClinicalTrials.gov (and five in CTIS), all recruiting or authorised at the cut-off.", "refs": [ "CTGOV", "CTIS", "PR2025C" ] }, { "n": 14, "claim": "It is being developed for treatment-resistant depression", "where": "Wikipedia, forums", "verdict": "PARTIAL", "evidence": "Partial match with the past: Takeda registered a treatment-resistant depression trial in 2017 (withdrawn, 0 enrolled) and described that target in 2020. The current programme enrols adults with major depressive disorder and inadequate response to at least one antidepressant.", "refs": [ "CT_TRD", "TAKEDA2020", "10K2025" ] }, { "n": 15, "claim": "It is legal or approved as a nootropic", "where": "forums, vendors", "verdict": "CONTRADICTED", "evidence": "Contradicted for approval: no marketing authorisation located at the FDA or the EMA; the developers describe it as investigational. National rules on possession or sale are not assessed here.", "refs": [ "OPENFDA", "EMAREP", "PR2025C" ] }, { "n": 16, "claim": "It is anxiolytic", "where": "r/NooTopics", "verdict": "NO_SOURCE", "evidence": "No human study has an anxiety endpoint. The only animal anxiety-like observations come from 3 stressed monkeys without a concurrent control group.", "refs": [ "40564108" ] }, { "n": 17, "claim": "It sharpens sensory perception or introspection", "where": "r/NooTopics", "verdict": "NO_SOURCE", "evidence": "Anecdotal. No endpoint in any registered trial.", "refs": [ "CTGOV" ] }, { "n": 18, "claim": "Ketamine-like antidepressant effect without psychotomimetic effects", "where": "forum posts citing the rat paper", "verdict": "PARTIAL", "evidence": "Partial match in rats (antidepressant-like behaviour in a social-submission model over 3 weeks, including when tested a day after administration; no hyperlocomotion at the levels tested) and in 24 healthy volunteers (no dissociation or euphoria adverse events). No comparison with ketamine in patients; the trial's open-label ketamine period was not compared statistically.", "refs": [ "34655652", "36153330", "34045439" ] }, { "n": 19, "claim": "What research-chemical vendors sell is the correct compound at high purity", "where": "r/Nootropics and similar", "verdict": "NOT_ASSESSABLE", "evidence": "Outside this literature. The one independent animal study bought material from a catalogue supplier and reports the supplier's purity; no independent analytical study of market material was located in PubMed.", "refs": [ "40564108" ] } ], "claim_counts": { "NO_SOURCE": 6, "PARTIAL": 6, "TRIAL_DATA": 1, "CONTRADICTED": 4, "SUPPORTED": 1, "NOT_ASSESSABLE": 1 }, "financial_interest": [ { "type": "direct", "party": "Takeda", "role": "Discoverer; patent families from 2010 and 2020; licensor; holds Japan since January 2025", "interest": "Eligible for up to USD 742.5 million in event-based milestones under the restated licence (the filing gives this figure for the agreement and does not break it down by compound), plus tiered royalties on Neurocrine's net sales of osavampator: mid-to-upper teens in the US and low double digits elsewhere, blended", "refs": [ "10Q2026", "8K2025" ] }, { "type": "direct", "party": "Neurocrine Biosciences", "role": "Licensee outside Japan; sponsor of SAVITRI and the phase 3 programme", "interest": "Expensed a USD 37.5 million milestone when phase 3 began (Q1 2025); entitled to royalties on Takeda's sales in Japan", "refs": [ "10Q2026", "10K2025" ] }, { "type": "indirect", "party": "XOMA Royalty", "role": "Takeda Revenue Share Agreement over a basket of development-stage Takeda assets, of which osavampator is one", "interest": "A low to mid-single-digit share of certain payments Takeda receives; USD 101 million is the aggregate potential milestone figure for three late-stage assets together (mezagitamab, osavampator, volixibat), not for osavampator alone", "refs": [ "XOMA10K" ] }, { "type": "indirect", "party": "Ligand Pharmaceuticals", "role": "Acquired XOMA Royalty on 14 July 2026", "interest": "Holds the XOMA portfolio, and with it the indirect interest above", "refs": [ "LGND10Q" ] } ], "patent_families": [ { "family": "Takeda compound family", "assignee": "Takeda", "priority": "2010-08-10 (JP2010179577)", "members": "WO2012020848A1; US 8,575,154 B2 (granted 2013-11-05); US 10,654,874 B2; US 11,279,713 B2; CN104926837A; EP2603513B1", "subject": "A genus of heterocyclic compounds of formula (I), or salts, with AMPA receptor potentiating action; the compound's systematic name appears in the text", "refs": [ "PAT2010", "PCPAT" ] }, { "family": "Takeda method-of-use family", "assignee": "Takeda", "priority": "2020-05-15", "members": "WO2021229294A1; TW202207944A; EP4149478A1", "subject": "Methods of treating depression or preventing relapse with the compound (administration details omitted)", "refs": [ "PAT2021", "PCPAT" ] }, { "family": "Third-party combination filings", "assignee": "Gilgamesh Pharmaceuticals; Sage Therapeutics", "priority": "2022-02-11 to 2022-02-28", "members": "WO2023154450A2 (Gilgamesh); WO2023158668A1, WO2023159035A1, EP4479032A1, CN119072304A, WO2023163879A1 (Sage)", "subject": "Compositions or combination methods (an AMPA PAM with an NMDA receptor antagonist; Sage's Compound (1) with an additional agent) in which the compound appears among candidate agents", "refs": [ "PCPAT" ] }, { "family": "Third-party delivery filings", "assignee": "Biora Therapeutics", "priority": "2019-12-13", "members": "EP3870261B1; EP4309722A2; US 11,707,610 B2", "subject": "Ingestible devices for delivering therapeutic agents to the gastrointestinal tract; the compound appears among listed agents", "refs": [ "PCPAT" ] } ], "ampa_pam_comparators": [ { "compound": "Org 26576 (MK-8777)", "developer": "Organon / Merck", "phase": "Phase 2", "indications": "Major depressive disorder (phase 1b/2, n = 54); adult ADHD (n = 67)", "result": "Depression: numerical MADRS improvement in an exploratory study. ADHD: one fixed-dose arm differed from placebo on the primary scale (p = 0.0147), the rising-dose arm did not (p = 0.59).", "stop_reason": "No reason for discontinuation located", "refs": [ "22954616", "CT_ORG" ] }, { "compound": "S 47445 (tulrampator)", "developer": "Servier", "phase": "Phase 2", "indications": "Alzheimer's disease with depressive symptoms (n = 520); adjunctive treatment in major depressive disorder (n = 400)", "result": "Alzheimer's trial: no difference from placebo on cognition, function or depressive symptoms at 24 weeks. Depression trial (n = 414): no difference from placebo on HAM-D change, with Holm adjustment for multiplicity (EU register results, 8 March 2018).", "stop_reason": "No reason located", "refs": [ "31297437", "CT_S47445", "EUCTR_S47445", "40840695" ] }, { "compound": "PF-04958242 / BIIB104 (pesampator)", "developer": "Pfizer, then Biogen", "phase": "Phase 2", "indications": "Age-related hearing loss (n = 44, crossover); ketamine-induced cognitive impairment in healthy men (n = 29); cognitive impairment associated with schizophrenia", "result": "Hearing loss: no change versus placebo. Healthy volunteers: reduced ketamine-induced memory impairment. Schizophrenia phase 2 (n = 195): no difference on the MATRICS composite (p = 0.85 and 0.81).", "stop_reason": "Earlier schizophrenia phase 2 terminated in 2016 for 'internal portfolio prioritization'", "refs": [ "25997115", "28242871", "CT_BIIB104", "CT_PF2016" ] }, { "compound": "LY451395 (mibampator)", "developer": "Eli Lilly", "phase": "Phase 2", "indications": "Cognition in Alzheimer's disease (n = 181); agitation and aggression in Alzheimer's disease (n = 132)", "result": "No difference from placebo on cognition (ADAS-Cog) or on the primary agitation scale.", "stop_reason": "No reason located", "refs": [ "17389305", "23257314" ] }, { "compound": "CX516 (Ampalex)", "developer": "Cortex Pharmaceuticals (now RespireRx)", "phase": "Phase 2", "indications": "Cognition in schizophrenia, add-on (n = 105); fragile X syndrome (n = 49)", "result": "Schizophrenia: no difference from placebo on the cognitive composite. Fragile X: no improvement in memory, the primary outcome; allergic rash in 12.5% of the active group.", "stop_reason": "No reason located", "refs": [ "17487227", "17069542" ] }, { "compound": "CX717", "developer": "Cortex Pharmaceuticals (now RespireRx)", "phase": "Phase 2a", "indications": "Adult ADHD (n = 68, crossover); sleep deprivation in healthy men (n = 16)", "result": "ADHD: primary analysis not significant (trend), a secondary analysis significant for one arm. Sleep deprivation: no consistent improvement in pre-specified analyses; reduced slow-wave sleep at the highest level.", "stop_reason": "No reason located", "refs": [ "40783159", "21940760" ] } ], "registry_checks": { "ctgov": "9 records (see trials)", "eu_ctr": "EudraCT 2021-003989-12 (SAVITRI), results v1 published 2025-10-26", "ctis": { "NBI-1065845": [ "2024-519418-29-00", "2024-519420-25-00", "2024-519421-37-00", "2024-519423-24-00", "2025-520541-72-00" ], "TAK-653": [], "osavampator": [] }, "jrct": "not verified: search could not be completed by script on 2026-10-25", "date": "2026-10-25" }, "changelog": [ { "version": "1.4", "date": "2026-10-25", "changes": [ "Phase 3 power analysis from SAVITRI confidence intervals (Figure 5).", "jRCT searched manually: 0 records.", "Independent recoding by a third coder added to Methods.", "Author figures added or redrawn (SAVITRI forest plot, trial Gantt chart, AMPA modulator panel).", "Target-engagement wording narrowed; dose-omission rule stated precisely; Takeda co-author count corrected to four of nine." ] }, { "version": "1.3", "date": "2026-10-25", "changes": [ "Full texts read for PMID 34655652, 36341809, 40840695 and 31378256 (obtained legally by the publisher route); 11 of 13 census records now classified from full text.", "Correction: the rat social-submission study ran for 3 weeks of repeated administration at a contract laboratory (10 pairs per group), not 6 days; '6 days' was the abstract's onset wording. Claims 6 and 18 and the unknowns list updated.", "Added from full texts: quantified agonist activity versus LY451646; BDNF increase in neurons only in the presence of AMPA; definition of the rat seizure margin and its comparison with TAK-137 and LY451646; effect in rats tested a day after administration; developer statements on attention and social behaviour in rodents; data-availability statement.", "Comparators: S 47445 depression trial results added from the EU Clinical Trials Register (n = 414, Holm-adjusted, no difference); developer assays placing LY451395 and PF-04958242 with the high-agonism comparator.", "Independent reviews: Pharmacol Res 2025 relied on the 2024 press release, noted that day-7 MADRS was not reported, described phase 3 as in TRD, and has a co-author leading a company developing another AMPA PAM; Adv Pharmacol 2019 stated that the structure was not yet disclosed." ] }, { "version": "1.2", "date": "2026-10-25", "changes": [ "RUO review: method-of-use patent row reduced to 'administration details omitted'; NCT03792672 endpoint wording without timing; claim 4 reworded ('Described on forums as an antidepressant') with new verdict 'Trial data exist (efficacy unproven)'; count now 1 supported, 1 trial data, 6 partly supported, 4 contradicted, 6 no source, 1 not assessable; SAVITRI plain-language summary attributed to the sponsor; declaration of interest states that Condor Research does not sell TAK-653; RUO box states that osavampator is not supplied by Condor Research." ] }, { "version": "1.1", "date": "2026-10-25", "changes": [ "SAVITRI results found on the EU Clinical Trials Register (EudraCT 2021-003989-12, posted 2025-10-26) and added as a sixth source; 'no registry results' corrected to 'no results on ClinicalTrials.gov'.", "SAVITRI described as two separate comparisons with placebo, with no dose-versus-dose comparison; nominal p values; the dose-split sensitivity check is stated not to cover all endpoints and time points; day-56 figures attributed source by source.", "ClinicalTrials.gov certification presented as a registry fact; removed from title, summary and key findings; no inference about approval, deadline or compliance.", "BDNF described as an inconsistent serum signal; ceiling effect attributed to the authors as a hypothesis; serum BDNF stated not to establish or exclude central signalling.", "CYP3A finding limited to the substrates and conditions studied, noting ratios outside the no-effect range.", "Financial interests split into direct (Takeda, Neurocrine) and indirect (XOMA basket share, Ligand by acquisition); USD 742.5 million and USD 101 million explained.", "Forum verdict scale made strict and uniform; claims 3, 4, 9, 10, 14 and 18 reworded; claim 10 now 'Contradicted' without qualifier; count unchanged at 1/7/4/6/1, with a new sensitivity on claim 14.", "Visible Research Use Only boundary before the human evidence; headings and FAQ reworded ('registered and published', 'reported').", "Added: CTIS and jRCT checks, patent family map, comparison with six clinical-stage AMPA modulators; 'What this dossier adds' limited to the sources reviewed.", "Removed repetition between key findings, SAVITRI section, conclusions and answer; added plain-language pauses.", "Registry markers recoloured neutral in Figures 1 and 3." ] }, { "version": "1.0-rc", "date": "2026-10-25", "changes": [ "First release candidate." ] } ], "regulatory": [ { "jurisdiction": "United States (FDA)", "status": "Investigational; no approval located", "basis": "openFDA Drugs@FDA query for 'osavampator' returned no match on 2026-10-25. Company reports an End-of-Phase 2 meeting completed by January 2025.", "refs": [ "OPENFDA", "PR2025A" ] }, { "jurisdiction": "European Union (EMA)", "status": "No authorisation or application located", "basis": "Not in the EMA medicines report downloaded 2026-10-25 (control: esketamine present).", "refs": [ "EMAREP" ] }, { "jurisdiction": "EU trial registries", "status": "SAVITRI results posted; 5 phase 3 trials authorised", "basis": "EU Clinical Trials Register: EudraCT 2021-003989-12 (SAVITRI), results v1 published 2025-10-26. CTIS public search (2026-10-25): 5 phase 3 entries for 'NBI-1065845', 0 for 'TAK-653' or 'osavampator'.", "refs": [ "EUCTR", "CTIS" ] }, { "jurisdiction": "Japan", "status": "Rights with Takeda since January 2025; no jRCT record", "basis": "jRCT (jrct.mhlw.go.jp) searched manually on 2026-10-25 for \"TAK-653\" and \"osavampator\": 0 records for each.", "refs": [ "PR2025A", "JRCT" ] }, { "jurisdiction": "World Anti-Doping Agency", "status": "Not named in the 2026 Prohibited List", "basis": "S0 prohibits at all times any pharmacological substance not addressed by another section and without current approval for human therapeutic use, including drugs under clinical development; on that wording an investigational substance such as this falls within S0.", "refs": [ "WADA2026" ] }, { "jurisdiction": "Names", "status": "INN and USAN: osavampator", "basis": "Listed as [INN], [USAN] and [WHO-DD] in PubChem; used by Neurocrine from 27 January 2025.", "refs": [ "PUBCHEM", "PR2025A" ] } ], "identity": { "Names and codes": "Osavampator (INN, USAN); TAK-653 (Takeda); NBI-1065845 (Neurocrine)", "PubChem CID": "56655833", "CAS number": "1358751-06-0", "UNII": "9E3TOE5RIZ", "ChEMBL": "CHEMBL4594403", "Molecular formula": "C19H23N3O3S", "Molecular weight": "373.5 g/mol", "IUPAC name": "9-(4-cyclohexyloxyphenyl)-7-methyl-3,4-dihydropyrazino[2,1-c][1,2,4]thiadiazine 2,2-dioxide", "InChIKey": "PXJBHEHFVQVDDS-UHFFFAOYSA-N", "Computed properties (PubChem)": "XLogP3 2.7; topological polar surface area 79.7 Ų; 0 hydrogen-bond donors; 5 acceptors", "Class": "Small molecule; positive allosteric modulator of the AMPA receptor with minimal agonist activity in the developer's assays. Not a peptide." }, "timeline": [ { "date": "2010-08-10", "category": "IP", "event": "Priority date of Takeda compound patent family" }, { "date": "2013-11-05", "category": "IP", "event": "US 8,575,154 B2 granted to Takeda" }, { "date": "2015-08-26", "category": "Clinical", "event": "First-in-human study starts (NCT02561156)" }, { "date": "2017-10-18", "category": "Clinical", "event": "TRD phase 2 registered; later withdrawn, 0 enrolled" }, { "date": "2018-12-06", "category": "Clinical", "event": "First-in-human results published as ACNP abstract" }, { "date": "2019-02-11", "category": "Clinical", "event": "TMS / NeuroCart trial starts (NCT03792672)" }, { "date": "2019-07-01", "category": "Literature", "event": "First independent mention (Adv Pharmacol 2019)" }, { "date": "2020-05-15", "category": "IP", "event": "Priority date of Takeda method-of-use family" }, { "date": "2020-06-12", "category": "Corporate", "event": "Takeda licenses the compound to Neurocrine" }, { "date": "2021-07-15", "category": "Literature", "event": "Developer pharmacology papers (2021)" }, { "date": "2021-12-06", "category": "Clinical", "event": "SAVITRI recruitment starts (EU register)" }, { "date": "2024-01-10", "category": "Clinical", "event": "SAVITRI primary completion" }, { "date": "2024-03-25", "category": "Registry", "event": "Delayed-results certification listed on ClinicalTrials.gov" }, { "date": "2024-04-23", "category": "Corporate", "event": "SAVITRI topline by press release" }, { "date": "2025-01-22", "category": "Clinical", "event": "First phase 3 trial starts (NCT06786624)" }, { "date": "2025-01-27", "category": "Corporate", "event": "Licence restated; Japan back to Takeda; INN in use" }, { "date": "2025-06-01", "category": "Literature", "event": "Only independent experimental study (3 macaques)" }, { "date": "2025-09-22", "category": "Corporate", "event": "SAVITRI poster at Psych Congress 2025" }, { "date": "2025-10-26", "category": "Registry", "event": "SAVITRI results posted on EU Clinical Trials Register" }, { "date": "2026-10-25", "category": "Cut-off", "event": "Dossier cut-off" }, { "date": "2027-07-01", "category": "Expected", "event": "Estimated primary completion, three acute phase 3 trials" }, { "date": "2029-05-01", "category": "Expected", "event": "Estimated primary completion, long-term safety study" } ], "phase3_countries": [ "Australia", "Belgium", "Bulgaria", "Canada", "Croatia", "Czechia", "Estonia", "Finland", "Hungary", "Italy", "Latvia", "Lithuania", "Netherlands", "Poland", "Romania", "Serbia", "Slovakia", "South Korea", "Spain", "Sweden", "Taiwan", "United Kingdom", "United States" ], "phase3_eu_member_states": [ "Belgium", "Bulgaria", "Croatia", "Czechia", "Estonia", "Finland", "Hungary", "Italy", "Latvia", "Lithuania", "Netherlands", "Poland", "Romania", "Slovakia", "Spain", "Sweden" ], "references": [ { "n": 1, "pmid": "40564108", "doi": "10.3390/biomedicines13061389", "cita": "Li L, Zhang Z, Liu X et al. TAK-653 Reverses Core Depressive Symptoms in Chronic Stress-Induced Monkey Model. Biomedicines. 2025;13(6).", "url": "https://pubmed.ncbi.nlm.nih.gov/40564108/" }, { "n": 2, "doc": "CTGOV", "cita": "ClinicalTrials.gov API v2: the 9 records retrieved with TAK-653, osavampator and NBI-1065845 (NCT numbers in Table 3).", "url": "https://clinicaltrials.gov/api/v2/studies?query.term=TAK-653%20OR%20osavampator%20OR%20NBI-1065845" }, { "n": 3, "doc": "EUCTR", "cita": "EU Clinical Trials Register. EudraCT 2021-003989-12 (NBI-1065845-MDD2024, SAVITRI): clinical trial results, version 1, published 26 October 2025.", "url": "https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-003989-12/results" }, { "n": 4, "doc": "CTIS", "cita": "Clinical Trials Information System (CTIS), public search API, 25 October 2026: 'NBI-1065845' returns 5 phase 3 trials (2024-519418-29-00, 2024-519420-25-00, 2024-519421-37-00, 2024-519423-24-00, 2025-520541-72-00); 'TAK-653' and 'osavampator' return 0.", "url": "https://euclinicaltrials.eu/ctis-public/search" }, { "n": 5, "doc": "OPENFDA", "cita": "US Food and Drug Administration. openFDA Drugs@FDA endpoint, queries openfda.generic_name and products.active_ingredients.name = osavampator (no match, 25 October 2026).", "url": "https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:osavampator" }, { "n": 6, "doc": "EMAREP", "cita": "European Medicines Agency. Medicines output: medicines report (xlsx), downloaded 25 October 2026; no entry for osavampator, TAK-653 or NBI-1065845.", "url": "https://www.ema.europa.eu/en/documents/report/medicines-output-medicines-report_en.xlsx" }, { "n": 7, "doc": "PUBCHEM", "cita": "PubChem. Osavampator, CID 56655833: synonyms and computed properties. National Library of Medicine.", "url": "https://pubchem.ncbi.nlm.nih.gov/compound/56655833" }, { "n": 8, "doc": "PAT2010", "cita": "Takeda Pharmaceutical Co Ltd. Heterocyclic compound and use thereof. WO2012020848A1; priority 10 August 2010, published 16 February 2012 (US 8,575,154 B2 granted 5 November 2013).", "url": "https://patents.google.com/patent/WO2012020848A1/en" }, { "n": 9, "doc": "PAT2021", "cita": "Takeda Pharmaceutical Co Ltd. Treatment for depression. WO2021229294A1; priority 15 May 2020, published 18 November 2021.", "url": "https://patents.google.com/patent/WO2021229294A1/en" }, { "n": 10, "doc": "PCPAT", "cita": "PubChem patent records linked to CID 56655833 (titles, assignees, priority dates and abstracts), retrieved via PUG-View 25 October 2026.", "url": "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/56655833/xrefs/PatentID/JSON" }, { "n": 11, "pmid": "42867279", "doi": "10.1080/13543776.2026.2748595", "cita": "Colson T, Pirotte B, Francotte P. Positive allosteric modulators of AMPA receptors: advances and emerging trends. Expert Opin Ther Pat. 2026:1-19.", "url": "https://pubmed.ncbi.nlm.nih.gov/42867279/" }, { "n": 12, "pmid": "34267258", "doi": "10.1038/s41598-021-93888-0", "cita": "Suzuki A, Kunugi A, Tajima Y et al. Strictly regulated agonist-dependent activation of AMPA-R is the key characteristic of TAK-653 for robust synaptic responses and cognitive improvement. Sci Rep. 2021;11(1):14532.", "url": "https://pubmed.ncbi.nlm.nih.gov/34267258/" }, { "n": 13, "pmid": "36341809", "doi": "10.1016/j.neuropharm.2022.109308", "cita": "Suzuki A, Hara H, Kimura H. Role of the AMPA receptor in antidepressant effects of ketamine and potential of AMPA receptor potentiators as a novel antidepressant. Neuropharmacology. 2023;222:109308.", "url": "https://pubmed.ncbi.nlm.nih.gov/36341809/" }, { "n": 14, "pmid": "34655652", "doi": "10.1016/j.pbb.2021.173289", "cita": "Hara H, Suzuki A, Kunugi A et al. TAK-653, an AMPA receptor potentiator with minimal agonistic activity, produces an antidepressant-like effect with a favorable safety profile in rats. Pharmacol Biochem Behav. 2021;211:173289.", "url": "https://pubmed.ncbi.nlm.nih.gov/34655652/" }, { "n": 15, "pmid": "34045439", "doi": "10.1038/s41398-021-01451-2", "cita": "O'Donnell P, Dijkstra FM, Damar U et al. Transcranial magnetic stimulation as a translational biomarker for AMPA receptor modulation. Transl Psychiatry. 2021;11(1):325.", "url": "https://pubmed.ncbi.nlm.nih.gov/34045439/" }, { "n": 16, "doc": "ACNP2018", "cita": "Asgharnejad M, Zicha S, Xu L, et al. M148. Pharmacokinetic and pharmacodynamic properties of the investigational AMPA receptor positive allosteric modulator TAK-653 after single and multiple rising doses in healthy volunteers. ACNP 57th Annual Meeting: Poster Session I. Neuropsychopharmacology. 2018;43(Suppl 1):S157. DOI 10.1038/s41386-018-0266-7.", "url": "https://doi.org/10.1038/s41386-018-0266-7" }, { "n": 17, "doc": "CTSAD", "cita": "ClinicalTrials.gov record NCT02561156, posted results (first posted 2019-02-08).", "url": "https://clinicaltrials.gov/study/NCT02561156" }, { "n": 18, "doc": "CT_TRD", "cita": "ClinicalTrials.gov record NCT03312894 (withdrawn, 0 participants, 'Business decision').", "url": "https://clinicaltrials.gov/study/NCT03312894" }, { "n": 19, "doc": "TAKEDA2020", "cita": "Takeda Pharmaceutical Company. Neurocrine Biosciences and Takeda Announce Collaboration to Develop and Commercialize Potential Therapies for Psychiatric Disorders. Press release, 16 June 2020.", "url": "https://www.takeda.com/newsroom/newsreleases/2020/neurocrine-biosciences-and-takeda-announce-collaboration-to-develop-and-commercialize--potential-therapies-for-psychiatric-disorders/" }, { "n": 20, "doc": "SECLIC", "cita": "Neurocrine Biosciences. Exclusive License Agreement with Takeda dated 12 June 2020, Exhibit 10.3 to Form 10-Q filed 3 August 2020 (portions redacted). SEC EDGAR.", "url": "https://www.sec.gov/Archives/edgar/data/914475/000091447520000018/nbix-20200630exhibit103.htm" }, { "n": 21, "doc": "PR2024", "cita": "Neurocrine Biosciences. Neurocrine Biosciences Reports Positive Phase 2 Data for NBI-1065845 in Adults with Major Depressive Disorder. Press release, 23 April 2024.", "url": "https://www.prnewswire.com/news-releases/neurocrine-biosciences-reports-positive-phase-2-data-for-nbi-1065845-in-adults-with-major-depressive-disorder-302123889.html" }, { "n": 22, "doc": "8K2025", "cita": "Neurocrine Biosciences. Form 8-K: Amended and Restated License Agreement with Takeda, filed 27 January 2025. SEC EDGAR.", "url": "https://www.sec.gov/Archives/edgar/data/914475/000091447525000006/nbix-20250124.htm" }, { "n": 23, "doc": "PR2025B", "cita": "Neurocrine Biosciences. Neurocrine Biosciences Announces Initiation of Phase 3 Registrational Program for Osavampator. Press release, 28 January 2025.", "url": "https://www.prnewswire.com/news-releases/neurocrine-biosciences-announces-initiation-of-phase-3-registrational-program-for-osavampator-as-an-adjunctive-therapy-for-the-treatment-of-major-depressive-disorder-in-adults-302361369.html" }, { "n": 24, "doc": "PR2026", "cita": "Neurocrine Biosciences. Neurocrine Biosciences Reports Second Quarter 2026 Financial Results. Press release, 30 July 2026.", "url": "https://www.prnewswire.com/news-releases/neurocrine-biosciences-reports-second-quarter-2026-financial-results-302839431.html" }, { "n": 25, "pmid": "36153330", "doi": "10.1038/s41398-022-02148-w", "cita": "Dijkstra F, O'Donnell P, Klaassen E et al. Central nervous system effects of TAK-653, an investigational alpha-amino-3-hydroxy-5-methyl-4-isoxazole receptor (AMPAR) positive allosteric modulator in healthy volunteers. Transl Psychiatry. 2022;12(1):408.", "url": "https://pubmed.ncbi.nlm.nih.gov/36153330/" }, { "n": 26, "pmid": "38700236", "doi": "10.1111/cts.13791", "cita": "Lin S, Ionescu A, Maynard-Scott J et al. Effects of the selective AMPA modulator NBI-1065845 on the pharmacokinetics of midazolam or ethinyl estradiol-levonorgestrel in healthy adults. Clin Transl Sci. 2024;17(5):e13791.", "url": "https://pubmed.ncbi.nlm.nih.gov/38700236/" }, { "n": 27, "doc": "CTTMS", "cita": "ClinicalTrials.gov record NCT03792672, posted results (first posted 2020-07-02).", "url": "https://clinicaltrials.gov/study/NCT03792672" }, { "n": 28, "doc": "POSTER", "cita": "Singh JB, Ge T, Ionescu A, et al. Osavampator (NBI-1065845/TAK-653) demonstrates statistically significant and clinically meaningful improvements in depression severity and is well tolerated in adults with major depressive disorder: phase 2 SAVITRI results. Poster 33, Psych Congress, San Diego, 17-21 September 2025 (PDF hosted by HMP Global Learning Network).", "url": "https://hmp-websites.s3.amazonaws.com/hmp_ln/2025-10/33%20-%20Osavampator%20NBI-1065845%20TAK-653%20Demonstrates%20Meaningful%20Improvements%20in%20Depression%20Severity%20and%20Is%20Well%20Tolerated%20in%20Adults%20With%20Major%20Depressive%20Disorder.pdf" }, { "n": 29, "doc": "ABSHMP", "cita": "Singh JB. Osavampator (NBI-1065845/TAK-653) Demonstrates Meaningful Improvements in Depression Severity and Is Well Tolerated in Adults With Major Depressive Disorder: Phase 2 SAVITRI Results. Psych Congress 2025 abstract page, HMP Global Learning Network, published 17 October 2025.", "url": "https://www.hmpgloballearningnetwork.com/node/347570" }, { "n": 30, "doc": "CTSAV", "cita": "ClinicalTrials.gov record NCT05203341 (SAVITRI), version of 2025-01-15, including the certification/extension (delayed results) fields; no results posted at 25 October 2026.", "url": "https://clinicaltrials.gov/study/NCT05203341" }, { "n": 31, "doc": "10K2025", "cita": "Neurocrine Biosciences. Form 10-K for fiscal year 2025, filed 11 February 2026. SEC EDGAR.", "url": "https://www.sec.gov/Archives/edgar/data/914475/000091447526000007/nbix-20251231.htm" }, { "n": 32, "doc": "PR2025C", "cita": "Neurocrine Biosciences. Neurocrine Biosciences Presents Positive New Data from Phase 2 Study of Osavampator in Adults with Major Depressive Disorder. Press release, 22 September 2025.", "url": "https://www.prnewswire.com/news-releases/neurocrine-biosciences-presents-positive-new-data-from-phase-2-study-of-osavampator-in-adults-with-major-depressive-disorder-302562476.html" }, { "n": 33, "doc": "CTMETA", "cita": "ClinicalTrials.gov API v2 data dictionary: dispFirstSubmitDate, 'Certification/Extension (aka Delayed Results) First Submitted Date'.", "url": "https://clinicaltrials.gov/api/v2/studies/metadata" }, { "n": 34, "doc": "JRCT", "cita": "Japan Registry of Clinical Trials (jRCT). Manual search for TAK-653 and osavampator, 25 October 2026: 0 records each; screenshots archived.", "url": "https://jrct.mhlw.go.jp/search" }, { "n": 35, "pmid": "31378256", "doi": "10.1016/bs.apha.2019.03.002", "cita": "Witkin JM, Martin AE, Golani LK et al. Rapid-acting antidepressants. Adv Pharmacol. 2019;86:47-96.", "url": "https://pubmed.ncbi.nlm.nih.gov/31378256/" }, { "n": 36, "pmid": "40840695", "doi": "10.1016/j.phrs.2025.107918", "cita": "Freudenberg F, Reif-Leonhard C, Dawson GR et al. All roads lead to glutamate: NMDA and AMPA receptors as targets for rapid-acting antidepressants. Pharmacol Res. 2025;220:107918.", "url": "https://pubmed.ncbi.nlm.nih.gov/40840695/" }, { "n": 37, "doc": "EPMC", "cita": "Europe PMC REST search for TAK-653, osavampator, NBI-1065845 and TAK653 in full text, 25 October 2026 (43 hits).", "url": "https://www.ebi.ac.uk/europepmc/webservices/rest/search?query=%22TAK-653%22%20OR%20osavampator%20OR%20%22NBI-1065845%22%20OR%20TAK653" }, { "n": 38, "pmid": "22954616", "doi": "10.1177/0269881112458728", "cita": "Nations KR, Dogterom P, Bursi R et al. Examination of Org 26576, an AMPA receptor positive allosteric modulator, in patients diagnosed with major depressive disorder: an exploratory, randomized, double-blind, placebo-controlled trial. J Psychopharmacol. 2012;26(12):1525-39.", "url": "https://pubmed.ncbi.nlm.nih.gov/22954616/" }, { "n": 39, "doc": "CT_ORG", "cita": "ClinicalTrials.gov records NCT00610649 (Org 26576 in major depressive disorder) and NCT00610441 (Org 26576 in adult ADHD, posted results).", "url": "https://clinicaltrials.gov/study/NCT00610441" }, { "n": 40, "pmid": "31297437", "doi": "10.1016/j.trci.2019.04.002", "cita": "Bernard K, Gouttefangeas S, Bretin S et al. A 24-week double-blind placebo-controlled study of the efficacy and safety of the AMPA modulator S47445 in patients with mild to moderate Alzheimer's disease and depressive symptoms. Alzheimers Dement (N Y). 2019;5:231-240.", "url": "https://pubmed.ncbi.nlm.nih.gov/31297437/" }, { "n": 41, "doc": "CT_S47445", "cita": "ClinicalTrials.gov records NCT02626572 and NCT02805439 (S 47445, Servier).", "url": "https://clinicaltrials.gov/study/NCT02805439" }, { "n": 42, "doc": "EUCTR_S47445", "cita": "EU Clinical Trials Register. EudraCT 2015-003867-13 (S 47445 as adjunctive treatment in major depressive disorder, Servier): clinical trial results, published 8 March 2018.", "url": "https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-003867-13/results" }, { "n": 43, "pmid": "25997115", "doi": "10.1001/jamaoto.2015.0791", "cita": "Bednar MM, DeMartinis N, Banerjee A et al. The Safety and Efficacy of PF-04958242 in Age-Related Sensorineural Hearing Loss: A Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2015;141(7):607-13.", "url": "https://pubmed.ncbi.nlm.nih.gov/25997115/" }, { "n": 44, "pmid": "28242871", "doi": "10.1038/mp.2017.6", "cita": "Ranganathan M, DeMartinis N, Huguenel B et al. Attenuation of ketamine-induced impairment in verbal learning and memory in healthy volunteers by the AMPA receptor potentiator PF-04958242. Mol Psychiatry. 2017;22(11):1633-1640.", "url": "https://pubmed.ncbi.nlm.nih.gov/28242871/" }, { "n": 45, "doc": "CT_BIIB104", "cita": "ClinicalTrials.gov record NCT03745820 (BIIB104 in cognitive impairment associated with schizophrenia, posted results).", "url": "https://clinicaltrials.gov/study/NCT03745820" }, { "n": 46, "doc": "CT_PF2016", "cita": "ClinicalTrials.gov record NCT02855411 (PF-04958242, terminated 22 September 2016, 'internal portfolio prioritization').", "url": "https://clinicaltrials.gov/study/NCT02855411" }, { "n": 47, "pmid": "17389305", "doi": "10.1212/01.wnl.0000260240.46070.7c", "cita": "Chappell AS, Gonzales C, Williams J et al. AMPA potentiator treatment of cognitive deficits in Alzheimer disease. Neurology. 2007;68(13):1008-12.", "url": "https://pubmed.ncbi.nlm.nih.gov/17389305/" }, { "n": 48, "pmid": "23257314", "doi": "10.1017/S1041610212002141", "cita": "Trzepacz PT, Cummings J, Konechnik T et al. Mibampator (LY451395) randomized clinical trial for agitation/aggression in Alzheimer's disease. Int Psychogeriatr. 2013;25(5):707-19.", "url": "https://pubmed.ncbi.nlm.nih.gov/23257314/" }, { "n": 49, "pmid": "17487227", "doi": "10.1038/sj.npp.1301444", "cita": "Goff DC, Lamberti JS, Leon AC et al. A placebo-controlled add-on trial of the Ampakine, CX516, for cognitive deficits in schizophrenia. Neuropsychopharmacology. 2008;33(3):465-72.", "url": "https://pubmed.ncbi.nlm.nih.gov/17487227/" }, { "n": 50, "pmid": "17069542", "doi": "10.1089/cap.2006.16.525", "cita": "Berry-Kravis E, Krause SE, Block SS et al. Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: a controlled trial. J Child Adolesc Psychopharmacol. 2006;16(5):525-40.", "url": "https://pubmed.ncbi.nlm.nih.gov/17069542/" }, { "n": 51, "pmid": "40783159", "doi": "10.1016/j.ejphar.2025.178047", "cita": "Radin DP, Cerne R, Smith JL et al. Low-impact ampakine CX717 exhibits promising therapeutic profile in adults with ADHD - A phase 2A clinical trial. Eur J Pharmacol. 2025;1005:178047.", "url": "https://pubmed.ncbi.nlm.nih.gov/40783159/" }, { "n": 52, "pmid": "21940760", "doi": "10.1177/0269881111405353", "cita": "Boyle J, Stanley N, James LM et al. Acute sleep deprivation: the effects of the AMPAKINE compound CX717 on human cognitive performance, alertness and recovery sleep. J Psychopharmacol. 2012;26(8):1047-57.", "url": "https://pubmed.ncbi.nlm.nih.gov/21940760/" }, { "n": 53, "doc": "FORUMS", "cita": "Public threads on Reddit (r/NooTopics, r/Nootropics, r/cognitiveTesting, r/antidepressants, r/cognitivescience, r/Biohackers), read as search excerpts on 25 October 2026; URLs in the dataset.", "url": "https://www.reddit.com/r/NooTopics/comments/vyb4kg/a_guide_to_ampa_positive_allosteric_modulators/" }, { "n": 54, "doc": "CENSUS", "cita": "Condor Research census of PubMed records, this dossier (dataset.json).", "url": "https://condorresearch.com/research/tak-653-osavampator-evidence/#census" }, { "n": 55, "doc": "10Q2026", "cita": "Neurocrine Biosciences. Form 10-Q for the quarter ended 30 June 2026, filed 31 July 2026. SEC EDGAR.", "url": "https://www.sec.gov/Archives/edgar/data/914475/000091447526000037/nbix-20260630.htm" }, { "n": 56, "doc": "XOMA10K", "cita": "XOMA Royalty Corp. Form 10-K for fiscal year 2025, filed 18 March 2026 (Takeda Revenue Share Agreement). SEC EDGAR.", "url": "https://www.sec.gov/Archives/edgar/data/791908/000110465926030872/xoma-20251231x10k.htm" }, { "n": 57, "doc": "LGND10Q", "cita": "Ligand Pharmaceuticals. Form 10-Q for the quarter ended 30 June 2026, filed 7 August 2026 (XOMA acquisition completed 14 July 2026). SEC EDGAR.", "url": "https://www.sec.gov/Archives/edgar/data/886163/000088616326000044/lgnd-20260630.htm" }, { "n": 58, "doc": "PR2025A", "cita": "Neurocrine Biosciences. Neurocrine Biosciences Announces Amendment to Strategic Collaboration with Takeda to Develop and Commercialize Osavampator. Press release, 27 January 2025.", "url": "https://www.prnewswire.com/news-releases/neurocrine-biosciences-announces-amendment-to-strategic-collaboration-with-takeda-to-develop-and-commercialize-osavampator-formerly-nbi-1065845tak-653-302360094.html" }, { "n": 59, "doc": "WADA2026", "cita": "World Anti-Doping Agency. International Standard: Prohibited List 2026, in force 1 January 2026, section S0 (Non-approved substances).", "url": "https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf" }, { "n": 60, "doc": "WIKI", "cita": "Wikipedia. Osavampator (revision of 20 August 2026).", "url": "https://en.wikipedia.org/wiki/Osavampator" }, { "n": 61, "pmid": "41057811", "doi": "10.1186/s12888-025-07141-3", "cita": "IsHak WW, Hirsch D, Renteria S et al. Depressive disorders: systematic review of approved psychiatric medications (2009-April 2025) and pipeline phase 3 medications. BMC Psychiatry. 2025;25(1):939.", "url": "https://pubmed.ncbi.nlm.nih.gov/41057811/" }, { "n": 62, "pmid": "42284011", "doi": "10.1007/s43440-026-00871-5", "cita": "Ziemichód W, Kajka N, Kister K et al. AMPA receptor modulation in depression: from molecular mechanisms of plasticity to therapeutic translation. Pharmacol Rep. 2026;78(4):1045-1057.", "url": "https://pubmed.ncbi.nlm.nih.gov/42284011/" }, { "n": 63, "pmid": "42645703", "doi": "10.1007/s40263-026-01330-8", "cita": "King A, Hardy M, Rhee TG et al. Next-Generation Pharmacotherapies for Unipolar Mood Disorders: A Leading Article on Phase II/III Drug Development Across Diverse Mechanisms. CNS Drugs. 2026;40(11):1429-1444.", "url": "https://pubmed.ncbi.nlm.nih.gov/42645703/" } ], "tables_in_text": [ "table-1 index", "table-2 human", "table-3 trials", "table-4 census", "table-5 claims", "table-6 savitri", "table-7 money", "table-8 regulatory", "table-9 identity", "table-10 kappa", "table-11 sensitivity", "table-12 adds", "table-13 patents", "table-14 comparators" ], "phase3_power_analysis": { "date": "2026-10-25", "assumptions": { "savitri_analysed": { "28": { "pbo": 91, "lower": 45, "higher": 47 }, "56": { "pbo": 79, "lower": 39, "higher": 40 } }, "sd_definition": "residual SD of the ANCOVA contrast, back-calculated from the 95% CI and analysed group sizes", "phase3_allocation": "1:1 assumed (not stated in the registry), 100 randomised per arm, 86.3 analysed per arm at SAVITRI day-56 retention (0.863)", "test": "two-sided, alpha 0.05, normal approximation", "independence": "two-of-three probability assumes independent trials with the same true difference" }, "phase3_trials": [ "NCT06786624", "NCT06911112", "NCT06963021" ], "savitri_implied": { "Day 28, lower dose": { "estimate": -4.3, "ci": [ -7.8, -0.8 ], "se": 1.786, "n_active": 45, "n_placebo": 91, "implied_residual_sd": 9.8 }, "Day 28, higher dose": { "estimate": -3.0, "ci": [ -6.4, 0.4 ], "se": 1.735, "n_active": 47, "n_placebo": 91, "implied_residual_sd": 9.66 }, "Day 56, lower dose": { "estimate": -7.5, "ci": [ -12.1, -2.9 ], "se": 2.347, "n_active": 39, "n_placebo": 79, "implied_residual_sd": 11.99 }, "Day 56, higher dose": { "estimate": -3.6, "ci": [ -8.0, 0.8 ], "se": 2.245, "n_active": 40, "n_placebo": 79, "implied_residual_sd": 11.57 } }, "sd_day28": 9.7, "sd_day56": 11.8, "minimum_detectable_difference_80pct": { "9.7": 4.14, "11.8": 5.03 }, "n_analysed_per_arm": 86.3, "scenarios": [ { "scenario": "SAVITRI lower dose, day 56 point estimate", "true_difference": 7.5, "power_sd9.7": 0.999, "p_two_of_three_sd9.7": 1.0, "power_sd11.8": 0.987, "p_two_of_three_sd11.8": 0.999 }, { "scenario": "SAVITRI higher dose, day 56 point estimate", "true_difference": 3.6, "power_sd9.7": 0.684, "p_two_of_three_sd9.7": 0.763, "power_sd11.8": 0.518, "p_two_of_three_sd11.8": 0.526 }, { "scenario": "SAVITRI lower dose, day 56, CI bound nearest zero", "true_difference": 2.9, "power_sd9.7": 0.502, "p_two_of_three_sd9.7": 0.502, "power_sd11.8": 0.365, "p_two_of_three_sd11.8": 0.302 }, { "scenario": "Two MADRS points", "true_difference": 2.0, "power_sd9.7": 0.273, "p_two_of_three_sd9.7": 0.183, "power_sd11.8": 0.2, "p_two_of_three_sd11.8": 0.104 } ] } }