Clinical trial NCT05463770: A Clinical Study That Will Assess the Effect of SEP-363856 and Prior Antipsychotic (PA) Standard of Care on Glucose and Regulation of Insulin in Patients With Schizophrenia
Official title: An Open-Label, Fixed Sequence, Multiple Dose Study of Glucose and Insulin Associated Parameters: SEP-363856 vs Prior Antipsychotic (PA) Standard of Care in Subjects With Schizophrenia Suffering From Metabolic Dysregulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schizophrenia
Keywords: schizophrenia
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2022-07-19
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an open-label, fixed sequence, multiple dose design.
Primary purpose: TREATMENT

Brief summary: A Clinical Study that will look at an investigational medication, SEP-363856 (called "study medication") in patients with schizophrenia and assess whether it changes:

* how the body processes (uses) glucose (blood sugar)
* how much insulin the pancreas can make. Insulin is a hormone that lowers blood sugar levels in the body.

The information from this study will help to understand any effect the study medication may have on how the body uses and stores glucose.

This study is accepting both male and female subjects. It will be held in approximately 6 locations in the United States. Participation could last up to 12 weeks.

Detailed description: This is an open-label, fixed sequence, multiple dose design. Following screening evaluations, subjects will check-in to the clinical research unit. After confirmation of continuation criteria, subjects will undergo an oral glucose tolerance test (oGTT), mixed meal tolerance test (MMTT) and spirulina breath test (GEBT). After these assessments are completed, subjects will have their prior antipsychotic (PA) or any other medication with psychotropic propensity washed out (dependent on their antipsychotic elimination half-life).

Subjects will undergo SEP-363856 titration schedule, followed by the oGTT, MMTT and GEBT tests during the SEP-363856 Stable Dose Period.

Subjects will be stabilized on their prior antipsychotic, discharged from the clinical research unit, and return to the unit for the follow-up visit 7 + 2 days after discharge.

Eligibility criteria: Inclusion Criteria: (this list is not all inclusive)

* Male or female subjects between 18 and 65 years of age, inclusive at time of 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 CGI-S score ≤ 4 (normal to moderately ill) at Screening
* Subject must have a PANSS total score ≤ 80 at Screening and a score of ≤ 4 on the following PANSS items at Screening: P7 (hostility) and G8 (uncooperativeness)
* Subjects' antipsychotic medication at screening must have had no dose change (minor dose adjustments for tolerability purposes are permitted) for at least eight weeks prior to the Screening visit.

Exclusion Criteria: (this list is not all inclusive)

-- Subject has a DSM-5 diagnosis or presence of symptoms consistent with a DSM-5 diagnosis other than schizophrenia or intellectual disability (IQ \< 70).

* Subject has attempted suicide within 12 months prior to Screening.
* 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 C-SSRS at Screening (ie. in the past 1 month) or at any subsequent C-SSRS assessment prior to dosing (ie, since last visit).
* Subject is at risk of harming him/herself or others according to the Investigator's judgment.

Primary outcomes:
measure: Change from baseline (PA) in oGTT derived plasma AUC0-120 min of glucose, insulin, c-peptide in oGTT to stable dose (SEP-363856) period assessment.
timeFrame: PA Baseline and SEP-363856 Stable Dose Period (up to 48 days)
measure: Change from baseline (PA) in mixed meal tolerance test (MMTT) derived plasma AUC0-240 min of glucose, insulin, c-peptide and β-cell responsivity index to stable dose (SEP-363856) period assessment.
timeFrame: PA Baseline and SEP-363856 Stable Dose Period (up to 48 days)
Secondary outcomes:
measure: Change from baseline (PA) in plasma AUC0-240 min and Cmax of acetaminophen levels to stable dose (SEP-363856) period assessment.
timeFrame: PA Baseline and SEP-363856 Stable Dose Period (up to 48 days)
measure: Change in Cmax of acetaminophen levels to stable dose (SEP-363856) period assessment.
timeFrame: PA Baseline and SEP-363856 Stable Dose Period (up to 48 days)
measure: Change in gastric emptying terminal elimination half-life (T1/2), baseline to stable dose (SEP-363856) period assessment.
timeFrame: PA Baseline and SEP-363856 Stable Dose Period (up to 48 days)
measure: Change in kPCD, baseline to stable dose (SEP-363856) period assessment
timeFrame: PA Baseline and SEP-363856 Stable Dose Period (up to 48 days)
measure: Change in the Visual Analog Scale (VAS) of fullness, hunger and satiety, baseline - repeat test (PA baseline to SEP-363856 stable dose period assessment) for all time points.
timeFrame: PA Baseline and SEP-363856 Stable Dose Period (up to 48 days)
measure: Change in lag time, baseline to stable dose (SEP-363856) period assessment
timeFrame: PA Baseline and SEP-363856 Stalbe Dose Period (up to 48 days)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Woodland International Research Group, LLC
state: Arkansas
city: Rogers
country: United States
facility: Woodland Research Northwest, LLC
state: Arkansas
city: Long Beach
country: United States
facility: Collaborative Neuroscience Research, LLC
state: California
city: Montclair
country: United States
facility: Catalina Research Institute LLC
state: California
city: San Diego
country: United States
facility: CNRI - San Diego LLC
state: California
city: Hialeah
country: United States
facility: Galiz Research
state: Florida
city: North Canton
country: United States
facility: Neuro-Behavioral Clinical Research, Inc.
state: Ohio
city: Richardson
country: United States
facility: Pillar Clinical Research, LLC
state: Texas
Study officials:
References: