A Phase 3, Multicenter, Two-part Study With a 5-week Double-blind Part (Randomized, Parallel-group, Placebo-controlled) Followed by a 12-week Open-label Extension Part, to Evaluate the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Chinese Adult Subjects With DSM-5 Schizophrenia

Karuna Therapeutics28 sites in 1 country202 target enrollmentMay 29, 2023

ConditionsSchizophrenia

InterventionsXanomeline and Trospium Chloride Capsules Placebo

DrugsXanomeline and Trospium Chloride Capsules Placebo

Overview

Phase: Phase 3
Intervention: Xanomeline and Trospium Chloride Capsules
Conditions: Schizophrenia
Sponsor: Karuna Therapeutics
Enrollment: 202
Locations: 28
Primary Endpoint: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Week 5 of the Double-Blind Period
Status: Completed
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

A Phase 3, Multicenter, Two-part Study with a 5-week Double-blind Part (Randomized, Parallel-group, Placebo-controlled) followed by a 12-week Open-label Extension Part, to Evaluate the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Chinese Adult Subjects with DSM-5 Schizophrenia

Registry

clinicaltrials.gov

Start Date

May 29, 2023

End Date

December 9, 2024

Last Updated

4 months ago

Study Type

Interventional

Study Design

Factorial

Sex

All

Investigators

Sponsor

Karuna Therapeutics

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subject is Chinese national, aged 18 to 65 years, inclusive, at screening.
•Subject is capable of providing written informed consent.
•Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 and MINI.
•Subject is experiencing an acute exacerbation or relapse of psychotic symptoms, with onset less than 2 months before screening.
•The subject requires hospitalization for this acute exacerbation or relapse of psychotic symptoms at screen.
•If already an inpatient at screening, hospitalization has to be ≤2 weeks for the current exacerbation at the time of screening.
•PANSS total score between 80 and 120,inclusive, with a scores of ≥4 (moderate or greater) for ≥2 of the following Positive Scale (P) items:
•Item 1 (P1; delusions)
•Item 2 (P2; conceptual disorganization)
•Item 3 (P3; hallucinatory behavior)

Exclusion Criteria

•Any primary DSM-5 disorder other than schizophrenia within 12 months before screening (confirmed using MINI version 7.0.2 at screening).
•Subjects who are newly diagnosed or are experiencing their first treated episode of schizophrenia.
•History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results.
•Subjects with human immunodeficiency virus (HIV), cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections based on either medical history or liver function test results.
•History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma.
•History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months.
•Risk for suicidal behavior during the study as determined by the investigator's clinical assessment and C-SSRS.
•Clinically significant abnormal findings on the physical examination, medical history, electrocardiogram, or clinical laboratory results at screening that, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results.
•Subjects are receiving or have recently received (within 5 half-lives or 1 week, whichever is longer, before baseline \[Day -1\]) oral antipsychotic medications; monoamine oxidase inhibitors; anticonvulsants (e.g., lamotrigine, valproate); tricyclic antidepressants (e.g., imipramine, desipramine); selective serotonin reuptake inhibitors; or any other psychoactive medications except for as-needed anxiolytics (e.g., lorazepam, chloral hydrate).
•Subjects are receiving or have recently received (within 1 week before baseline \[Day -1\]) metformin.

Arms & Interventions

KarXT

Intervention: Xanomeline and Trospium Chloride Capsules

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Week 5 of the Double-Blind Period

Time Frame: At Baseline and at Week 5 of the Double-Blind Period

PANSS Total Score is a clinical tool used to measure the severity of symptoms in individuals with schizophrenia. It includes 30 items divided into three subscales: Positive Symptoms (e.g., hallucinations, delusions) Negative Symptoms (e.g., social withdrawal, lack of motivation) General Psychopathology (e.g., anxiety, depression) Each item is rated from 1 (absent) to 7 (extreme), resulting in a total score range from 30 to 210. Higher PANSS Total Scores indicate more severe symptoms and worse clinical outcomes. Baseline is defined as last non-missing assessment prior to the first dose of study drug.

Secondary Outcomes

Change From Baseline in Positive Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period(At Baseline and at Week 5 of the Double-Blind Period)
Change From Baseline in Negative Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period(At Baseline and at Week 5 of the Double-Blind Period)
Change From Baseline in Negative Marder Factor Score of the Positive and Negative Syndrome Scale (PANSS) at Week 5 of the Double-Blind Period(At Baseline and at Week 5 of the Double-Blind Period)
Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score at Week 5 of the Double-Blind Period(At Baseline and at Week 5 of the Double-Blind Period)
Percentage of PANSS Responders (≥30% Change in PANSS Total Score From Baseline) at Week 5 of the Double-Blind Period(At Baseline and at Week 5 of the Double-Blind Period)
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Week 12 of the Open-Label Period(At Baseline and at Week 12 of the Open-Label Period)
Change From Baseline in Positive Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period(At Baseline and at Week 12 of the Open-Label Period)
Change From Baseline in Negative Symptom Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period(At Baseline and at Week 12 of the Open-Label Period)
Change From Baseline in Negative Marder Factor Score of the Positive and Negative Syndrome Scale (PANSS) at Week 12 of the Open-Label Period(At Baseline and at Week 12 of the Open-Label Period)
Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score at Week 12 of the Open-Label Period(At Baseline and at Week 12 of the Open-Label Period)
Percentage of PANSS Responders (≥30% Change in PANSS Total Score From Baseline) at Week 12 of the Open-Label Period(At Baseline and at Week 12 of the Open-Label Period)
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Drug Withdrawal(From first dose until study completion (up to approximately 18 weeks))
Number of Participants With Orthostatic Vital Sign Events(From first dose until study completion (up to approximately 18 weeks))
Number of Participants With Elevated Liver Function Test Results(At study baseline, Day 21 DB, Day 35 DB, open-label baseline, Day 14 OL, Day 84 OL, and end of study visit (up to approximately 18 weeks))
Number of Participants With Elevated Metabolic Syndrome Parameters(At study baseline, Day 21 DB, Day 35 DB, open-label baseline, Day 14 OL, Day 84 OL, and end of study visit (up to approximately 18 weeks))
Number of Participants With Abnormal Electrocardiogram (ECG) Results(At study baseline and up to study completion (up to approximately 18 weeks))
Number of Participants With Suicidal Ideation as Defined by a Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score of 1 or Greater(From first dose to study completion (up to approximately 18 weeks))
Number of Participants With Clinically Meaningful Changes in Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS) Results(At study baseline, open-label baseline, and up to study completion (up to approximately 18 weeks))
Change From Baseline in Body Weight(At study baseline, Day 35 DB, open-label baseline, Day 84 OL, and end of study visit (up to approximately 18 weeks))
Change From Baseline in Body Mass Index (BMI)(At study baseline, Day 35 DB, open-label baseline, Day 84 OL, and end of study visit (up to approximately 18 weeks))
Change From Baseline in Waist Circumference(At study baseline, Day 35 DB, open-label baseline, Day 84 OL, and end of study visit (up to approximately 18 months))
Area Under the Concentration-Time Curve (AUC0-12) of Xanomeline and Trospium - Double-Blind Period(On Day 28 of the Double-Blind Period)
Maximum Observed Plasma Concentration (Cmax) of Xanomeline and Trospium - Double-Blind Period(On Day 28 of the Double-Blind Period)
Time to Cmax (Tmax) of Xanomeline and Trospium - Double-Blind Period(On Day 28 of the Double-Blind Period)