SEP-363856 for Schizophrenia

No longer recruiting at 7 trial locations

Overseen By CNS Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sunovion

Must be taking: Antipsychotics

Disqualifiers: Other DSM-5 diagnosis, Suicide risk, others

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the medication SEP-363856 (also known as SEP-856 or Ulotaront) causes physical dependence in adults with schizophrenia, a mental disorder affecting thoughts, feelings, and behaviors. Researchers will randomly assign participants to receive either the experimental drug or a placebo (a harmless, inactive pill). The study seeks individuals diagnosed with schizophrenia who have been on antipsychotic medication for at least six weeks and have their symptoms under control. The trial will occur at several locations in the United States and will last about 10 weeks.

As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that participants must have been on an antipsychotic for at least 6 weeks before the trial without changes. This suggests you may need to continue your current antipsychotic medication.

Is there any evidence suggesting that SEP-363856 is likely to be safe for humans?

Research has shown that SEP-363856, also known as ulotaront, may help treat schizophrenia with manageable safety concerns. One study found that higher doses of ulotaront improved symptoms of schizophrenia without increasing safety risks, indicating that the treatment is generally well-tolerated.

In another study over a 4-week period, ulotaront was well-tolerated, with fewer participants experiencing unwanted side effects compared to those taking a placebo. Specifically, 45.8% of participants taking ulotaront had side effects, while a higher percentage of those on placebo did.

Overall, these studies suggest that SEP-363856 is relatively safe for people with schizophrenia. However, as this is an early-phase trial, ongoing research will continue to evaluate its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for schizophrenia?

Most treatments for schizophrenia, like antipsychotics, work by blocking dopamine receptors. But SEP-363856 works differently, targeting both the trace amine-associated receptor 1 (TAAR1) and serotonin receptors. This unique mechanism could offer a new way to manage symptoms with potentially fewer side effects. Researchers are excited about SEP-363856 because it might provide relief for patients who don't respond well to existing medications.

What evidence suggests that SEP-363856 might be an effective treatment for schizophrenia?

Research has shown that SEP-363856, also known as ulotaront, offers promising results for treating schizophrenia. One study found that this medication significantly improved both the positive and negative symptoms of schizophrenia. Another study demonstrated that doses around 100 mg improved symptoms without increasing safety risks. Long-term use of ulotaront also led to continued improvement in symptoms. A key study showed that a daily dose of 50-75 mg effectively reduced symptoms. In this trial, participants will receive either SEP-363856 or a placebo. These findings suggest that SEP-363856 could be a helpful treatment option for schizophrenia. ^{1 2 3 4 6}

Who Is on the Research Team?

CNS Medical Director

Principal Investigator

Sumitomo Pharma America, Inc.

Are You a Good Fit for This Trial?

Adults aged 18-65 with schizophrenia, who are relatively stable (not severely ill) and have been on antipsychotic medication for at least 6 weeks can join this study. They must not be at risk of suicide or self-harm, nor have other mental health diagnoses besides schizophrenia.

Inclusion Criteria

Subject must have a CGI-S score ≤ 4 at Screening and Day 1

Subject must have a PANSS total score ≤ 80 at Screening and specific PANSS items at Screening

I have been diagnosed with schizophrenia.

Exclusion Criteria

Subject has attempted suicide within 6 months prior to Screening

Subject has active suicidal ideation or specific plan on the C-SSRS assessment

Subject is at significant risk of harming self or others according to the Investigator's judgment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Treatment

Participants receive SEP-363856 or placebo in a double-blind, placebo-controlled, randomized withdrawal study

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• SEP-363856

Trial Overview The trial is testing SEP-363856 to see if it causes physical dependence compared to a placebo. Participants will be randomly assigned to receive either the drug or a placebo over approximately 10 weeks across six sites in the US.

How Is the Trial Designed?

Group I: SEP-363856 Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Sunovion

Lead Sponsor

Trials

190

Recruited

48,900+

Dr. Armin Szegedi

Sunovion

Chief Medical Officer since 2023

MD from Semmelweis University

Dr. Antony Loebel

Sunovion

Chief Executive Officer since 2019

MD from Washington University School of Medicine

Otsuka Pharmaceutical Development & Commercialization, Inc.

Lead Sponsor

Trials

271

Recruited

170,000+

John Kraus

Otsuka Pharmaceutical Development & Commercialization, Inc.

Chief Medical Officer since 2023

MD, PhD

Tarek Rabah

Otsuka Pharmaceutical Development & Commercialization, Inc.

Chief Executive Officer since 2022

BS in Biology and BA in Business from the American University of Beirut, MBA from McGill University

Sumitomo Pharma America, Inc.

Lead Sponsor

Trials

244

Recruited

51,500+

Jatin Shah

Sumitomo Pharma America, Inc.

Chief Medical Officer since 2024

MD from an unspecified institution

Tsutomu Nakagawa

Sumitomo Pharma America, Inc.

Chief Executive Officer since 2024

MBA from Waseda University

Published Research Related to This Trial

In a study of 450 patients with schizophrenia receiving placebo injections, a 10%-15% reduction in the PANSS total score after the first week was found to be a strong predictor of long-term response at week 9, indicating that early improvements can help identify potential placebo responders.

Patients with better judgment and insight at baseline (lower PANSS G12 scores) were also more likely to show a placebo response, suggesting that certain demographic and clinical characteristics may influence the effectiveness of placebo treatments in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Placebo Improvement Is a Marker for Subsequent Placebo Response in Long-Acting Injectable Antipsychotic Trials for Schizophrenia: Combined Analysis of 4 RCTs. Kumagai, F., Suzuki, T., Fleischhacker, WW., et al.[2019]

In a pooled analysis of two 6-week trials involving 422 patients with schizophrenia, early response to antipsychotic treatment (low-dose olanzapine or haloperidol) significantly distinguished active drug from placebo, with a greater mean reduction in psychiatric symptoms observed at 2 weeks.

The study suggests that shortening the duration of placebo-controlled trials from 6 weeks to 2-4 weeks is feasible for identifying efficacy in acutely ill patients, as early treatment response was predictive of overall treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early onset of antipsychotic action in schizophrenia: evaluating the possibility of shorter acute efficacy trials. Kinon, BJ., Chen, L., Stauffer, VL., et al.[2021]

The placebo effect in schizophrenia clinical trials is becoming a significant challenge, making it harder to detect the effectiveness of new treatments and increasing development costs.

Understanding the central nervous system mechanisms behind the placebo effect and improving study designs could help mitigate this issue and enhance the reliability of clinical trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-related effects in clinical trials in schizophrenia: what is driving this phenomenon and what can be done to minimize it? Alphs, L., Benedetti, F., Fleischhacker, WW., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8660889/

Safety and effectiveness of ulotaront (SEP-363856) in ... Specifically, the results of this long-term study indicate that ulotaront treatment was associated with sustained improvement in psychotic ...

2. academic.oup.com academic.oup.com/ijnp/article/28/9/pyaf059/8228252

Trajectory of efficacy and safety across ulotaront dose levels in ... We found that higher doses—especially around 100 mg—can improve schizophrenia symptoms without increasing safety concerns. These findings are important because ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02969369

NCT02969369 | A Study to Evaluate the Efficacy, Safety ... This is a multicenter, randomized, parallel-group, placebo-controlled study evaluating the efficacy, safety, and tolerability of double-blind SEP-363856 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37165101/

Ulotaront: review of preliminary evidence for the efficacy ... In the double-blind, placebo-controlled, acute study, ulotaront was associated with significant (p < 0.001) improvement in Positive and Negative ...

5. news.us.sumitomo-pharma.com news.us.sumitomo-pharma.com/2020-04-15-New-England-Journal-of-Medicine-Publishes-Pivotal-Results-Evaluating-Sunovions-SEP-363856-for-the-Treatment-of-Schizophrenia

New England Journal of Medicine Publishes Pivotal ... In this study, once-daily, flexible-dose (50-75 mg) treatment with SEP-363856 demonstrated a statistically significant and clinically meaningful ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01994473

NCT01994473 | Study Assessing the Safety, Tolerability, ... This is a study designed to evaluate the safety, tolerability, and PK of SEP-363856 and its metabolite SEP-363854 in male and female subjects with schizophrenia ...