NCT02969382

A Study to Evaluate the Efficacy and Safety of SEP-363856 in Acutely Psychotic Adults 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 245 participants. Completed in 31 July 2018.

Timeline

5 December 2016

Primary endpoint
31 July 2018

31 July 2018

Quick facts

Lead sponsor	Otsuka Pharmaceutical Development & Commercialization, Inc.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	245
Start date	5 December 2016
Primary completion	31 July 2018
Estimated completion	31 July 2018
Sites	33 locations across Russia, Ukraine, Hungary, Romania, United States

Drugs / interventions tested

• SEP-363856 — full drug profile →
• Placebo - Cap — full drug profile →

Conditions studied

• Schizophrenia — all drugs for Schizophrenia →

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.

Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 Primary · Baseline, Week 4

PANSS 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. Higher PANSS total score means more severe outcome.

Group	Value	95% CI
Placebo	-9.7	± 1.61
SEP-363856	-17.2	± 1.66

Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 4 Secondary · Baseline, Week 4

The CGI-S 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.

Group	Value	95% CI
Placebo	-0.5	± 0.09
SEP-363856	-1.0	± 0.09

Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Subscale Score at Week 4 Secondary · Baseline, Week 4

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. Higher PANSS Positive subscale score means more severe outcome.

Group	Value	95% CI
Placebo	-3.9	± 0.51
SEP-363856	-5.5	± 0.53

Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Subscale Score at Week 4 Secondary · Baseline, Week 4

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. Higher PANSS Negative subscale score means more severe outcome.

Group	Value	95% CI
Placebo	-1.6	± 0.41
SEP-363856	-3.1	± 0.42

Change From Baseline in Positive and Negative Syndrome Scale (PANSS) General Psychopathology Subscale Score at Week 4 Secondary · Baseline, Week 4

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. Higher PANSS General Psychopathology subscale score means more severe out

Group	Value	95% CI
Placebo	-4.7	± 0.84
SEP-363856	-9.0	± 0.87

Change From Baseline in Brief Negative Symptom Scale (BNSS) Total Score at Week 4 Secondary · Baseline, Week 4

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. Higher BNSS total score means more severe outcome.

Group	Value	95% CI
Placebo	-2.7	± 0.91
SEP-363856	-7.1	± 0.95

Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 4 Secondary · Baseline, Week 4

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). Higher MADRS total score means more severe outcome.

Group	Value	95% CI
Placebo	-1.6	± 0.57
SEP-363856	-3.3	± 0.59

Positive and Negative Syndrome Scale (PANSS) Response at Week 4, Defined as a 20% or Greater Improvement From Baseline in PANSS Total Score Secondary · Baseline, Week 4

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. Higher PANSS total score means more severe outcome.

Group	Value	95% CI
Placebo	44
SEP-363856	62

The Incidence of Overall AEs, Serious AEs (SAEs) and AEs (or SAEs) Leading to Discontinuation Secondary · From first dose of study drug to last study visit, up to 5 weeks

Overall Adverse Events (AEs)

Group	Value	95% CI
Placebo	63
SEP-363856	55

Serious Adverse Events (SAEs)

Group	Value	95% CI
Placebo	3
SEP-363856	2

AEs/SAEs leading to discontinuation from study

Group	Value	95% CI
Placebo	8
SEP-363856	11

AEs/SAEs leading to discontinuation of study drug

Group	Value	95% CI
Placebo	8
SEP-363856	10

Frequency of Subjects With Suicidal Ideation Using the Columbia - Suicide Severity Rating Scale (C-SSRS) Secondary · Overall post-Baseline double-blind treatment period, up to 4 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.

Group	Value	95% CI
Placebo	2
SEP-363856	0

Frequency of Subjects With Suicidal Behavior Using the Columbia - Suicide Severity Rating Scale (C-SSRS) Secondary · Overall post-Baseline double-blind treatment period, up to 4 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.

Group	Value	95% CI
Placebo	1
SEP-363856	0

Frequency of Subjects With Suicidality Using the Columbia - Suicide Severity Rating Scale (C-SSRS) Secondary · Overall post-Baseline double-blind treatment period, up to 4 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.

Group	Value	95% CI
Placebo	2
SEP-363856	0

Adverse events — posted to ClinicalTrials.gov

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

Placebo

Serious: 3/125 (2%)

Deaths: 0/125

SEP-363856

Serious: 2/120 (2%)

Deaths: 1/120

Serious adverse events (3 terms)

Reaction	System	Placebo	SEP-363856
Schizophrenia	Psychiatric disorders	—	—
Cardiovascular insufficiency	Cardiac disorders	—	—
Suicide attempt	Psychiatric disorders	—	—

Other adverse events (7 terms — click to expand)

Reaction	System	Placebo	SEP-363856
Headache	Nervous system disorders	—	—
Insomnia	Psychiatric disorders	—	—
Anxiety	Psychiatric disorders	—	—
Somnolence	Nervous system disorders	—	—
Schizophrenia	Psychiatric disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Agitation	Psychiatric disorders	—	—

Most-reported serious reactions: Schizophrenia, Cardiovascular insufficiency, Suicide attempt.

Data from ClinicalTrials.gov NCT02969382 adverse events section.

Sponsor's own description

A study to evaluate the efficacy and safety of an experimental drug (SEP-363856) in acutely psychotic adults with schizophrenia

Publications & conference data

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

1. A Non-D2-Receptor-Binding Drug for the Treatment of Schizophrenia.
   Koblan KS, Kent J, Hopkins SC, Krystal JH, et al · · 2020 · cited 216× · PMID 32294346 · DOI 10.1056/nejmoa1911772
2. 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
3. The future of psychopharmacology: a critical appraisal of ongoing phase 2/3 trials, and of some current trends aiming to de-risk trial programmes of novel agents.
   Correll CU, Solmi M, Cortese S, Fava M, et al · · 2023 · cited 90× · PMID 36640403 · DOI 10.1002/wps.21056
4. 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
5. 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
6. New Developments in the Treatment of Schizophrenia: An Expert Roundtable.
   Kantrowitz JT, Correll CU, Jain R, Cutler AJ. · · 2023 · cited 23× · PMID 36932673 · DOI 10.1093/ijnp/pyad011
7. Novel 1-Amidino-4-Phenylpiperazines as Potent Agonists at Human TAAR1 Receptor: Rational Design, Synthesis, Biological Evaluation and Molecular Docking Studies.
   Francesconi V, Cichero E, Kanov EV, Laurini E, et al · · 2020 · cited 22× · PMID 33202687 · DOI 10.3390/ph13110391
8. 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