SEP-363856 for Schizophrenia

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

60 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug SEP-363856 (Ulotaront) for treating schizophrenia?

Research shows that Ulotaront, a new type of drug, may help improve symptoms in people with schizophrenia, including positive symptoms (like hallucinations), negative symptoms (like lack of motivation), and depressive symptoms, without the common side effects of other antipsychotics. ^{1 2 3 4 5}

Is ulotaront (SEP-363856) safe for humans?

Ulotaront (SEP-363856) has been studied in healthy adults and patients with schizophrenia, showing it is well-absorbed and generally safe with no significant side effects reported in the studies. It was tested in various doses and formulations, and no major safety concerns were identified. ^{1 2 3 5 6}

What makes the drug SEP-363856 unique for treating schizophrenia?

SEP-363856, also known as Ulotaront, is unique because it does not work like traditional antipsychotics that target dopamine receptors. Instead, it has a novel mechanism of action that may offer benefits for patients who do not respond well to standard treatments. ^{7 8 9 10 11}

What is the purpose of this trial?

This trial tests if a schizophrenia medication called SEP-363856 causes dependence in adults aged 18-65.

Research Team

CNS Medical Director

Principal Investigator

Sumitomo Pharma America, Inc.

Eligibility Criteria

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

I have been on the same antipsychotic medication for at least 6 weeks.

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

Exclusion Criteria

Subject has attempted suicide within 6 months prior to Screening

I have a mental health condition that is not schizophrenia.

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

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

A Phase I, Open-Label, Fixed Sequence Study to Investigate the Effect of Cytochrome P450 2D6 Inhibition on the Pharmacokinetics of Ulotaront in Healthy Subjects. [2023]

2. England pubmed.ncbi.nlm.nih.gov

A sensitive LC-MS/MS method for simultaneous quantification of ulotaront and its N-desmethyl metabolite in human plasma and application to a clinical study. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Comparative Bioequivalence of Tablet and Capsule Formulations of Ulotaront and the Effect of Food on the Pharmacokinetics of the Tablet Form in Humans. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Ulotaront: a TAAR1/5-HT1A agonist in clinical development for the treatment of schizophrenia. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

In Vitro ADME and Preclinical Pharmacokinetics of Ulotaront, a TAAR1/5-HT1A Receptor Agonist for the Treatment of Schizophrenia. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic analysis of ulotaront in subjects with schizophrenia. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Early onset of antipsychotic action in schizophrenia: evaluating the possibility of shorter acute efficacy trials. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Roluperidone for the Treatment of Negative Symptoms of Schizophrenia. [2022]

9. United States 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. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Is the ongoing use of placebo in relapse-prevention clinical trials in schizophrenia justified? [2016]

11. England 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? [2021]