Efficacy and Safety Evaluation of Ulotaront (SEP-363856) in Acutely Psychotic Schizophrenia Patients: A Randomized, Double-Blind, Placebo-Controlled Study
- Trial ID
- 2022-503006-20-00
- Protocol
- DA801201
- Sponsor
- Sumitomo Pharma Co. Ltd.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of fixed doses of SEP-363856 (50 and 75 mg/day) compared with placebo in acutely psychotic patients with **schizophrenia**. This is measured by the Positive and Negative Syndrome Scale (PANSS) total score, which is a critical tool for assessing the severity of schizophrenia symptoms. Understanding the efficacy of SEP-363856 in this context is clinically relevant as it may offer a new therapeutic option for managing acute psychotic episodes in schizophrenia, potentially improving patient outcomes and quality of life.
Secondary objectives include evaluating the efficacy of the same fixed doses of SEP-363856 compared with placebo in the same patient population, as measured by the Clinical Global Impression-Severity (CGI-S) score. This secondary measure provides additional insights into the overall severity of the patient's condition and the potential impact of the treatment on their clinical status.
Participants
The clinical trial involves a total of **448 participants** diagnosed with **schizophrenia**, specifically targeting acutely psychotic patients. The study population includes both male and female subjects, aged between 18 to 65 years. Participants were selected based on their ability to provide informed consent and meet the DSM-5 criteria for schizophrenia, confirmed through clinical interviews. The trial includes individuals experiencing an acute exacerbation of psychotic symptoms, with a Positive and Negative Syndrome Scale (PANSS) total score of 80 or higher. The participants' general health status is characterized by a Clinical Global Impression-Severity (CGI-S) score of 4 or more, indicating they are moderately ill. The trial does not specify particular lifestyle considerations such as diet or physical activity. The study population is considered vulnerable, and the selection process ensures that participants understand the study's objectives, procedures, and potential risks and benefits.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled**, and **parallel-group** study to evaluate the efficacy and safety of SEP-363856 in acutely psychotic patients with **schizophrenia**. The trial will be conducted in multiple centers and will include a fixed-dose regimen. The study is divided into two phases: a double-blind phase followed by an open-label extension phase. The primary objective is to assess the efficacy of SEP-363856 at doses of 50 mg and 75 mg per day compared to placebo, using the Positive and Negative Syndrome Scale (PANSS) total score as the primary efficacy endpoint. The trial is expected to start recruitment on March 1, 2024, and conclude by June 30, 2025.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of schizophrenia according to DSM-5, and specific PANSS scores. The double-blind phase will last for 6 weeks, during which participants will receive either SEP-363856 or a matching placebo. Follow-up visits will occur at regular intervals to monitor safety and efficacy, with assessments including changes in PANSS and Clinical Global Impressions-Severity (CGI-S) scores. The primary endpoint will be evaluated at Week 6, focusing on the change from baseline in PANSS total score.
Upon completion of the double-blind phase, participants who meet the criteria will enter the open-label extension phase, where all will receive SEP-363856. The total duration of participant involvement is up to 18 weeks, including both phases. Conditions for early termination from the study include significant adverse events, withdrawal of consent, or non-compliance with study procedures. The study aims to provide comprehensive data on the efficacy and safety of SEP-363856 in the target population, contributing to the understanding and management of acute psychotic episodes in schizophrenia.
Treatment
The clinical trial involves the administration of **SEP-363856**, an experimental medication containing the active substance **ulotaront**. This medication is provided in a **tablet** form and is administered **orally**. The trial evaluates two fixed doses of SEP-363856: **50 mg** and **75 mg** per day. The maximum daily dose for the 50 mg regimen is 50 mg, with a total maximum dose of 6300 mg over the treatment period. For the 75 mg regimen, the maximum daily dose is 75 mg, with a total maximum dose of 9375 mg. The treatment period for both dosing regimens is up to **18 weeks**. The medication is manufactured by Sumitomo Pharma Co., Ltd., and the active substance is of chemical origin. Participant compliance with the dosing schedule is monitored throughout the study.
The study also includes a **placebo** group, which receives a **matching placebo** tablet. The placebo is designed to be indistinguishable from the active medication in appearance and administration route, ensuring the integrity of the double-blind study design. The placebo is administered orally, following the same dosing schedule as the active treatment groups. The inclusion of a placebo group allows for a controlled comparison to evaluate the efficacy and safety of SEP-363856 in patients with schizophrenia.
Efficacy
The efficacy of SEP-363856 in acutely psychotic patients with **schizophrenia** will be assessed using the Positive and Negative Syndrome Scale (PANSS) total score. The primary efficacy endpoint is the change from baseline in the PANSS total score at Week 6. Additionally, a secondary efficacy endpoint will evaluate the change from baseline in the Clinical Global Impression-Severity (CGI-S) score at Week 6. These assessments will be conducted in a randomized, double-blind, placebo-controlled, fixed-dose, multicenter study.
The PANSS and CGI-S scores will be collected at baseline and at the 6-week mark to determine the efficacy of the treatment. The PANSS is a validated scale commonly used in clinical trials to measure symptom severity in schizophrenia, while the CGI-S provides a clinician-rated assessment of the patient's overall severity of illness. The study will involve fixed doses of SEP-363856 (50 mg and 75 mg per day) compared to a placebo, with the aim of determining the drug's efficacy in reducing psychotic symptoms.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Inclusion criteria for the double-blind phase: Must be fully informed of and understand the objectives, procedures, and possible benefits and risks of the study, and give written informed consent prior to performing any study-related activities. If the subject is considered a minor according to local regulations at the time of collection of the informed consent, written consent will be obtained from a legally acceptable representative (guardian) in addition to that obtained from the subject.
- Male or female between 18 to 65 years of age (inclusive) at the time of consent.
- Must meet DSM-5 criteria for schizophrenia as established by clinical interview at Screening (using the DSM-5 as a reference and confirmed using the Structured Clinical Interview for DSM-5-Clinical Trials Version [SCID-5-CT]).
- Must have a CGI-S score ≥ 4 (moderately ill) at Screening and Baseline.
- Must have a PANSS total score ≥ 80 and a PANSS item score ≥ 4 (moderate) on 2 or more of the following PANSS items: delusions (P1), conceptual disorganization (P2), hallucinations (P3), and unusual thought content (G9) at Screening and Baseline.
- Must have an acute exacerbation of psychotic symptoms (no longer than 2 months prior to providing informed consent for this study). The acute exacerbation should include: - Marked deterioration of functioning in one or more areas, such as occupational, social, or personal care or hygiene. - In the case that the subject has been hospitalized for the purpose of treating an acute psychotic exacerbation at the timing of Screening, the duration must be no more than 2 consecutive weeks immediately before Screening.
- Subjects with more than 3 prior lifetime inpatient hospitalization for the treatment of an acute exacerbation of schizophrenia may be eligible only after approval with the Medical Monitor.
- Inclusion criteria for the open-label phase: 1. Must have completed the 6-week study treatment and all scheduled assessments at Visit 9 in the double-blind phase. 2. Female subjects of childbearing potential must have a negative urine pregnancy test at Visit 9. 3. Female subjects of childbearing potential must agree to use highly effective and reliable contraception throughout the study and for at least 30 days after the last dose of study drug has been taken. In the Investigator’s judgment, the subject will adhere to this requirement. 4. Male subjects must agree to avoid fathering a child and use highly effective methods of birth control from Screening until at least 30 days after the last study drug administration.
Exclusion Criteria
- Exclusion criteria for the double-blind phase: Have a decrease (improvement of symptoms) of ≥ 20% on the PANSS total score between Screening and Baseline.
- Have a DSM-5 diagnosis or presence of symptoms consistent with a DSM-5 diagnosis other than schizophrenia. Exclusionary disorders include but are not limited to alcohol use disorder (within past 12 months), substance (other than nicotine or caffeine) use disorder within past 12 months, or lifetime history of significant substance abuse that, in the opinion of the Investigator, may have had a significant and potentially permanent impact on the brain or other body systems, major depressive disorder, bipolar I or II disorder, schizoaffective disorder, obsessive compulsive disorder, and posttraumatic stress disorder. Symptoms of mild to moderate mood dysphoria or anxiety are allowed so long as these symptoms have not been a focus of primary treatment.
- Judged to be resistant to antipsychotic treatment by the Investigator, based on failure to respond to 2 or more marketed antipsychotic agents within a 1-year period prior to Screening, given at adequate dose as per labeling, for at least 4 weeks (28 consecutive days).
- Answer “yes” to “Suicidal Ideation” Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) on the C-SSRS assessment at Screening (ie, in the past month [30 days]) or at Baseline (ie, since last visit).
- At significant risk of harming self, others, or objects based on Investigator’s judgment.
- Have attempted suicide within 6 months prior to Screening.
- Subject is involuntarily hospitalized.
- Have received a total dose of antipsychotic medication equivalent to ≥ 12.0 mg/day of haloperidol for the majority of current episode (acute exacerbation). If receiving antipsychotic medication equivalent to ≥ 12.0 mg/day of haloperidol has been for less than 2 weeks, and the reason for the high dose was to temporarily control the subject due to acute agitation or similar need to manage the subject, the subject may be eligible after consultation with the Medical Monitor.
- Have any clinically significant unstable medical condition or any clinically significant chronic disease that in the opinion of the Investigator, would limit the subject’s ability to complete and/or participate in the study.
- Exclusion criteria for the open-label phase: 1. Answer “yes” to “Suicidal Ideation” Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) on the C-SSRS assessment at Visit 9. 2. Have a clinically significant abnormality including PE, vital signs, ECG, or laboratory test at Visit 9 that the Investigator in consultation with the Medical Monitor considers to be inappropriate to allow participation in the study. 3. In the opinion of the Investigator, subjects who are unsuitable in any other way to participate in this study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Romania | Not Recruiting | 01 Mar 2024 | 32 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
SEP-363856 | Test | TABLET | ORAL | 75 | 18 | PRD10267263 |
SEP-363856 matching placebo | Placebo | N/A | — | — | — | N/A |
SEP-363856 | Test | TABLET | ORAL | 50 | 18 | PRD10226746 |