A Clinical Trial Study to Determine the Effect of an Investigational Drug (SEP-363856) Has on the Way That the Drug Metformin Travels Through the Body in People With Schizophrenia.

A Randomized, Single-blind, Two-period Crossover to Investigate the Effect of SEP-363856 on the Pharmacokinetics of Metformin in Subjects With Schizophrenia.

A clinical trial study to determine the effect of an investigational drug (SEP-363856) has on the way that the drug Metformin travels through the body in people with schizophrenia. This clinical trial will have approximately 24 subjects both male and female 18 year of age and older. This study will be conducted in approximately 2 study sites in the United States.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: placebo; Drug: metformin; Drug: SEP-363856

Detailed Description

This is a randomized, single-blind, two-period crossover study in which each subject will receive both treatments and therefore act as their own control to minimize confounding covariates within the study population. Randomizing subjects to treatment sequence will assist with reducing the potential order effects that might confound the findings if all the subjects received the same treatment sequence. The single-blind method is used to keep subjects blind to treatment assignment throughout the study period, in order to avoid possible influence of the psychological factors of subjects on study assessments. This clinical study will evaluate whether SEP 363856 influences the PK of a concomitantly administered OCT2 substrate, metformin.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Oakland Park, Florida, United States, 33334
      • At Fort Lauderdale Behavioral Health Center
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Hassman Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subject between 18 and 65 years of age, inclusive, at the time of informed consent.
• Subject meets Diagnostic and Statistical Manual of Mental Disorders (DSM 5) criteria for a primary diagnosis of schizophrenia as established by clinical interview (using the DSM 5 as a reference and confirmed using the Structured Clinical Interview for DSM 5, Clinical Trials Version [SCID CT]).
• Subject must have a Clinical Global Impressions - Severity Scale (CGI S) score ≤ 4 (normal to moderately ill) at Screening.
• Subject must have a Positive and Negative Syndrome Scale (PANSS) total score ≤ 80 at Screening.
• Subject must have a score of ≤ 4 on the following PANSS items at Screening:

P7 (hostility) G8 (uncooperativeness).

• Subject must have normal to mild symptoms on all individual items of the Simpson-Angus Scale (SAS) (< 2), Abnormal Involuntary Movement Scale (AIMS) (< 3) and Barnes Akathisia Rating Scale (BARS) (< 3) at Screening.
• Subject has been taking an antipsychotic for at least six weeks prior to Screening and has had no change in antipsychotic medication(s) (minor dose adjustments for tolerability purposes may be permitted after Medical Monitor and Sponsor review) for at least six weeks prior to Screening.

Exclusion Criteria:

• Subject has 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, including any clinically significant hematological (including deep vein thrombosis) or bleeding disorder, renal, metabolic, endocrine, pulmonary, gastrointestinal, urological, cardiovascular, hepatic, neurologic or allergic disease (except for untreated seasonal allergies that are asymptomatic at the time of dosing).

  • Subject has a disorder or history of a condition, or previous gastrointestinal surgery (eg, cholecystectomy, vagotomy, bowel resection) that may interfere with drug absorption, distribution, metabolism, excretion, gastrointestinal motility, or pH, or a history of clinically significant abnormality of the hepatic or renal system, or a history of malabsorption (uncomplicated cholecystectomy, appendectomy, and hernia repair will be acceptable).
  • Subject has 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, 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 are not the primary focus of treatment.
  • Subject answers "yes" to "Suicidal Ideation" Items 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 Columbia-Suicide Severity Rating Scale (C SSRS) at Screening (ie, in the past 1 month) or at any subsequent C SSRS assessment prior to dosing (ie since last visit).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo and metformin; single dose of placebo + single dose of metformin-HCl 850 mg (approximately 663 mg metformin) (placebo will be dosed 1 hour prior to metformin administration)	Drug: placebo; single dose of placebo; Drug: metformin; metformin-HCl 850 mg
Experimental: SEP-363856 and metformin; single dose of SEP 363856 100 mg + single dose of metformin-HCl 850 mg (SEP 363856 will be dosed 1 hour prior to metformin administration)	Drug: metformin; metformin-HCl 850 mg; Drug: SEP-363856; single dose of SEP 363856 100 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration-time curve	area under the plasma concentration-time curve from time zero to infinity (AUC0 ∞) or area under the plasma concentration-time curve from time zero to a defined time (AUC0-t), if appropriate	72 hours
• maximum observed plasma concentration	maximum observed plasma concentration (Cmax).	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
area under the plasma concentration-time curve	area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration (AUC0-last)	72 hours
time of the maximum observed plasma concentration	time of the maximum observed plasma concentration (tmax)	72 hours
time of last quantifiable concentration	time of last quantifiable concentration (Tlast)	72 hours
• percentage of extrapolated AUC0-∞	percentage of extrapolated AUC0-∞ (%AUCextrap)	72 hours
terminal elimination half-life	terminal elimination half-life(T1/2)	72 hours
apparent clearance	apparent clearance (CL/F)	72 hours
apparent volume of distribution	apparent volume of distribution (VZ/F)	72 hours
amount excreted in urine	amount excreted in urine (Ae)	72 hours
percentage excreted in urine	percentage excreted in urine (Fe)	72 hours
renal clearance	renal clearance (CLR)	72 hours

Collaborators and Investigators

• Sponsor: Sunovion

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2021
• Primary Completion (Actual): May 3, 2022
• Study Completion (Actual): May 3, 2022

Study Registration Dates

• First Submitted: April 26, 2021
• First Submitted That Met QC Criteria: April 28, 2021
• First Posted (Actual): April 29, 2021

Study Record Updates

• Last Update Posted (Actual): June 2, 2022
• Last Update Submitted That Met QC Criteria: May 31, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: SEP361-110

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study may be made available upon request via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available upon request within 12 months of posting the study results on ct.gov.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No