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NCT02970929

An Extension Study of Safety and Tolerability of SEP-363856 in Adult Subjects With Schizophrenia

Completed Phase 2 Results posted Last updated 5 July 2024
What this trial tests

Phase 2 trial testing SEP-363856 in Schizophrenia in 157 participants. Completed in 29 January 2019.

Timeline
31 January 2017
Primary endpoint
29 January 2019
29 January 2019

Quick facts

Lead sponsorOtsuka Pharmaceutical Development & Commercialization, Inc.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment157
Start date31 January 2017
Primary completion29 January 2019
Estimated completion29 January 2019
Sites30 locations across Russia, Ukraine, Hungary, Romania, United States

Drugs / interventions tested

Conditions studied

Sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc. — full company profile →

Who can join

Adults 18 to 40, any sex, with Schizophrenia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

The Incidence of Overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation Primary · From first dose of study drug to last study visit (27 weeks)

Number of Participants with overall Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) leading to discontinuation

Overall Adverse Events (AEs)
GroupValue95% CI
SEP-36385688
Serious Adverse Events (SAEs)
GroupValue95% CI
SEP-36385615
Adverse Events leading to discontinuation from study
GroupValue95% CI
SEP-36385618
Adverse Events leading to discontinuation of study drug
GroupValue95% CI
SEP-36385618
Frequency of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) Secondary · Overall post Open-label Baseline treatment period (26 weeks)

Number of participants with suicidal ideation (SI) and suicidal behavior (SB) using the Columbia - Suicide Severity Rating Scale (C-SSRS). The C-SSRS is a tool designed to systematically assess and track suicidal behavior and suicidal ideation for life time, one month prior to the screening visit for suicidal ideation and 6 months prior to the screening visit for suicidal behavior, and throughout the study. The strength of this suicide classification system is in its ability to comprehensively identify suicidal events while limiting the over-identification of suicidal behavior.

Any suicidal ideation
GroupValue95% CI
SEP-3638563
Any suicidal behavior
GroupValue95% CI
SEP-3638561
Any suicidality
GroupValue95% CI
SEP-3638563
Severity of Suicidal Ideation (SI) and Suicidal Behavior (SB) Using the Columbia - Suicide Severity Rating Scale (C-SSRS) Secondary · Overall post Open-label Baseline treatment period (26 weeks)

The C-SSRS is a tool designed to systematically assess and track suicidal behavior and suicidal ideation for life time, one month prior to the screening visit for suicidal ideation and 6 months prior to the screening visit for suicidal behavior, and throughout the study. The strength of this suicide classification system is in its ability to comprehensively identify suicidal events while limiting the over-identification of suicidal behavior.

SI: Wish to be dead
GroupValue95% CI
SEP-3638562
SI: Non-specific active suicidal thoughts
GroupValue95% CI
SEP-3638562
SI: Any methods (not plan) without intent to act
GroupValue95% CI
SEP-3638560
SI: Some intent to act, without specific plan
GroupValue95% CI
SEP-3638560
SI: Specific plan and intent
GroupValue95% CI
SEP-3638560
SB: Preparatory acts or behavior
GroupValue95% CI
SEP-3638560
SB: Aborted attempt
GroupValue95% CI
SEP-3638561
SB: Interrupted attempt
GroupValue95% CI
SEP-3638560
Time to Relapse During the 26-week Open-label Treatment Period for Subjects Who Demonstrated a Clinical Response to 4 Weeks of Treatment With SEP-363856 Secondary · From the time of clinical response to relapse or censor (one day after the last study drug dose)

Relapse is defined as the earliest occurrence of any of the following: - An increase in PANSS total score by ≥ 30% from the PANSS total score at clinical response and a CGI-S score ≥ 3; - Re-hospitalization for worsening of psychosis; - Emergence of suicidality, homicidality, and/or risk of harm to self or others.

GroupValue95% CI
PBO-SEPNANA – NA
SEP-SEPNANA – NA
Rate of Relapse During the 26-week Open-label Treatment Period for Subjects Who Demonstrated a Clinical Response to 4 Weeks of Treatment With SEP-363856 Secondary · From the time of clinical response to relapse or censor (one day after the last study drug dose)

Relapse is defined as the earliest occurrence of any of the following: - An increase in PANSS total score by ≥ 30% from the PANSS total score at clinical response and a CGI-S score ≥ 3; - Re-hospitalization for worsening of psychosis; - Emergence of suicidality, homicidality, and/or risk of harm to self or others.

GroupValue95% CI
PBO-SEP12
SEP-SEP11
Changes From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Positive and Negative Syndrome Scale (PANSS) Total Score and Subscale Scores (Positive, Negative, and General Psychopathology) Secondary · Double-blind Baseline (DB BLN), Open-label Baseline (OL BLN), Week 26 (Wk 26)

PANSS is comprised of 30 items and 3 subscales (Positive, Negative, General Psychopathology). An anchored Likert scale from 1 - 7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. Individual items are then summed to determine scores for the 3 subscales, as well as a total score. PANSS Positive subscale score range: 7-49. PANSS Negative subscale score range: 7-49. PANSS General Psychopathology subscale score range: 16-112. PANSS total score range: 30-210.

Total Score: DB BLN Observed
GroupValue95% CI
SEP-363856101.5± 7.99
Total Score: OL BLN Observed
GroupValue95% CI
SEP-36385683.1± 15.03
Total Score: Wk 26 Observed
GroupValue95% CI
SEP-36385659.3± 12.45
Total Score: Chg from DB BLN at Wk 26
GroupValue95% CI
SEP-363856-41.8± 13.98
Total Score: Chg from OL BLN at Wk 26
GroupValue95% CI
SEP-363856-22.6± 15.48
Positive SS: DB BLN Observed
GroupValue95% CI
SEP-36385625.7± 3.22
Positive SS: OL BLN Observed
GroupValue95% CI
SEP-36385619.8± 4.96
Positive SS: Wk 26 Observed
GroupValue95% CI
SEP-36385612.2± 3.72
Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Clinical Global Impression - Severity (CGI-S) Score Secondary · Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26

The CGI-S is a single-item clinician-rated assessment of the subject's current illness state on a 7-point scale (score range: 1-7), where a higher score is associated with greater illness severity.

CGI-S Score: DB Baseline Observed
GroupValue95% CI
SEP-3638565.0± 0.42
CGI-S Score: OL Baseline Observed
GroupValue95% CI
SEP-3638564.0± 0.84
CGI-S Score: Week 26 Observed
GroupValue95% CI
SEP-3638563.0± 0.74
CGI-S Score: Change from DB Baseline at Week 26
GroupValue95% CI
SEP-363856-2.0± 0.82
CGI-S Score: Change from OL Baseline at Week 26
GroupValue95% CI
SEP-363856-1.0± 0.91
Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Brief Negative Symptom Scale (BNSS) Total Score Secondary · Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26

The BNSS is a rating scale to measure the current level of severity of negative symptoms in schizophrenia and schizoaffective disorder. The measure is comprised of 13 individual items organized in 6 subscales. The 13 individual items provide a composite total score (ranging from 0 to 78). Each of the items are scored on a Likert-type 7-point scale from 0 - 6, where values of 0 indicates symptom is absent and a value of 6 means the symptom is a severe form.

Total Score: DB Baseline Observed
GroupValue95% CI
SEP-36385638.4± 11.94
Total Score: OL Baseline Observed
GroupValue95% CI
SEP-36385633.0± 11.41
Total Score: Week 26 Observed
GroupValue95% CI
SEP-36385622.5± 11.83
Total Score: Change from DB Baseline at Week 26
GroupValue95% CI
SEP-363856-16.8± 12.42
Total Score: Change from OL Baseline at Week 26
GroupValue95% CI
SEP-363856-11.3± 9.69
Change From Double-blind Baseline of Study SEP361-201 and Open-label Baseline of Study SEP361-202 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score Secondary · Double-blind (DB) Baseline, Open-label (OL) Baseline, Week 26

The MADRS is a clinician-rated assessment of the subject's level of depression. The measure contains 10 items that measure apparent and reported sadness, inner tension, reduced sleep and appetite, difficulty concentrating, lassitude, inability to feel, and pessimistic and suicidal thoughts. Each item is scored in a range of 0 to 6 points, with higher scores indicating increased depressive symptoms. Total score will be equal to the sum of the 10 items (range between 0 and 60).

Total Score: DB Baseline Observed
GroupValue95% CI
SEP-36385612.6± 7.25
Total Score: OL Baseline Observed
GroupValue95% CI
SEP-3638569.2± 6.33
Total Score: Week 26 Observed
GroupValue95% CI
SEP-3638564.4± 4.72
Total Score: Change from DB Baseline at Week 26
GroupValue95% CI
SEP-363856-8.1± 6.44
Total Score: Change from OL Baseline at Week 26
GroupValue95% CI
SEP-363856-4.5± 5.28
Proportion of Subjects Who Achieved a Response, Defined as a 20% or Greater Improvement in Positive and Negative Syndrome Scale (PANSS) Total Score From Double-blind Baseline of Study SEP361-201 Secondary · Week 26

PANSS is comprised of 30 items and 3 subscales (Positive, Negative, General Psychopathology). An anchored Likert scale from 1 - 7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. Individual items are then summed to determine scores for the 3 subscales, as well as a total score. PANSS Positive subscale score range: 7-49. PANSS Negative subscale score range: 7-49. PANSS General Psychopathology subscale score range: 16-112. PANSS total score range: 30-210.

GroupValue95% CI
PBO-SEP52
SEP-SEP49

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug to last study visit (27 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

SEP-363856
Serious: 15/156 (10%)
Deaths: 0/156

Serious adverse events (6 terms)

ReactionSystemSEP-363856
SchizophreniaPsychiatric disorders
Acute psychosisPsychiatric disorders
DepressionPsychiatric disorders
Psychotic disorderPsychiatric disorders
Suicidal ideationPsychiatric disorders
Uterine haemorrhageReproductive system and breast disorders
Other adverse events (4 terms — click to expand)

ReactionSystemSEP-363856
HeadacheNervous system disorders
InsomniaPsychiatric disorders
SchizophreniaPsychiatric disorders
AnxietyPsychiatric disorders

Most-reported serious reactions: Schizophrenia, Acute psychosis, Depression, Psychotic disorder, Suicidal ideation, Uterine haemorrhage.

Data from ClinicalTrials.gov NCT02970929 adverse events section.

Sponsor's own description

An extension study of safety and tolerability of SEP-363856 in adult subjects with schizophrenia

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders.
    Wong TS, Li G, Li S, Gao W, et al · · 2023 · cited 113× · PMID 37137892 · DOI 10.1038/s41392-023-01427-2
  2. New and emerging treatments for schizophrenia: a narrative review of their pharmacology, efficacy and side effect profile relative to established antipsychotics.
    Lobo MC, Whitehurst TS, Kaar SJ, Howes OD. · · 2022 · cited 74× · PMID 34838528 · DOI 10.1016/j.neubiorev.2021.11.032
  3. Safety and effectiveness of ulotaront (SEP-363856) in schizophrenia: results of a 6-month, open-label extension study.
    Correll CU, Koblan KS, Hopkins SC, Li Y, et al · · 2021 · cited 69× · PMID 34887427 · DOI 10.1038/s41537-021-00190-z
  4. Ulotaront: review of preliminary evidence for the efficacy and safety of a TAAR1 agonist in schizophrenia.
    Achtyes ED, Hopkins SC, Dedic N, Dworak H, et al · · 2023 · cited 38× · PMID 37165101 · DOI 10.1007/s00406-023-01580-3
  5. Depicting Safety Profile of TAAR1 Agonist Ulotaront Relative to Reactions Anticipated for a Dopamine D2-Based Pharmacological Class in FAERS.
    Hopkins SC, Ogirala A, Worden M, Koblan KS. · · 2021 · cited 19× · PMID 34751928 · DOI 10.1007/s40261-021-01094-7
  6. Unlocking the Therapeutic Potential of Ulotaront as a Trace Amine-Associated Receptor 1 Agonist for Neuropsychiatric Disorders.
    Kuvarzin SR, Sukhanov I, Onokhin K, Zakharov K, et al · · 2023 · cited 17× · PMID 37509616 · DOI 10.3390/biomedicines11071977
  7. Pharmacological Treatment of Cognitive Impairment Associated With Schizophrenia: State of the Art and Future Perspectives.
    Vita A, Nibbio G, Barlati S. · · 2024 · cited 13× · PMID 39144119 · DOI 10.1093/schizbullopen/sgae013
  8. In Vitro ADME and Preclinical Pharmacokinetics of Ulotaront, a TAAR1/5-HT<sub>1A</sub> Receptor Agonist for the Treatment of Schizophrenia.
    Xiao G, Chen YL, Dedic N, Xie L, et al · · 2022 · cited 12× · PMID 35484370 · DOI 10.1007/s11095-022-03267-1

Verify or expand the search:

Other trials of SEP-363856

Trials testing the same drug.

Other recruiting trials for Schizophrenia

Currently open trials in the same condition.

Other Otsuka Pharmaceutical Development & Commercialization, Inc. trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02970929.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing