A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Adjunctive KarXT in Subjects With Inadequately Controlled Symptoms of Schizophrenia

Karuna Therapeutics161 sites in 1 country396 target enrollmentNovember 12, 2021

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: 396
Locations: 161
Primary Endpoint: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

Brief Summary

This is a Phase 3, 6-week, randomized, double-blind, placebo-controlled, multicenter, outpatient study in subjects with schizophrenia with an inadequate response to their current atypical antipsychotic treatment. The primary objective of the study is to assess the efficacy of adjunctive KarXT (a fixed dose combination of xanomeline and trospium chloride twice daily [BID]) versus placebo in the treatment of subjects with inadequately controlled symptoms of schizophrenia as measured by the Positive and Negative Syndrome Scale (PANSS) Total Score.

Registry

clinicaltrials.gov

Start Date

November 12, 2021

End Date

March 19, 2025

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Karuna Therapeutics

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subject is aged ≥18 to \<65 years at the time of randomization
•Subject is capable of providing signed Informed Consent Form before any study assessments will be performed
•Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 criteria and confirmed by Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorder Studies (MINI) version 7.0.2
•Subject is currently being treated with stable dosing of monotherapy risperidone, paliperidone, aripiprazole, or their LAIs ziprasidone, lurasidone, or cariprazine and has been taking this treatment with the same dosing regimen for at least 8 weeks at the time of Day 1 (Visit 3)
•The subject has had at least 1 previous inadequate response to above antipsychotics that was dosed appropriately (within the label) for at least 6 weeks
•The subject has not required psychiatric hospitalization, incarceration in prison, acute crisis intervention, or other increase in the level of care due to symptom exacerbation within 8 weeks of Screening and is psychiatrically stable in the opinion of the Investigator
•To be eligible for randomization, subjects need to have detectable levels of background antipsychotic medication (measured at Visit 1)
•Positive and Negative Syndrome Scale (PANSS) total score ≥ 70 at Screening and randomization
•Clinical Global Impression-Severity (CGI-S) scale with a score ≥ 4 (moderate) at Screening and randomization
•PANSS Marder Positive symptom factor ≥ 4 on 2 (or more) items (PANSS items, delusions, hallucinations, grandiosity, suspiciousness and persecution, stereotyped thinking, somatic concern, unusual thought content or lack of judgment and insight), at Screening and randomization

Exclusion Criteria

•Any primary DSM-5 disorder other than schizophrenia within 12 months before screening (confirmed using MINI version 7.0.2 at screening)
•The subject has a history of moderate to severe substance use disorder (other than nicotine) within the past 12 months
•A Screening subject with mild substance use disorder within the 12 months before Screening must be discussed with the Medical Monitor before being allowed into the study
•Subjects who test positive for cannabis at Screening may be permitted to enroll in consultation with the Medical Monitor if the subject's pattern of use is not indicative of a moderate to severe substance use disorder
•Subject has a history of treatment-resistant schizophrenia defined as:
•a. Failure to minimally respond to 2 adequate courses of antipsychotic drug (APD) pharmacotherapy Note: Failure to minimally respond is defined as persistence symptoms of moderate severity in 2 or more psychotic symptom domains or persistence of severe symptoms in 1 or more psychotic symptom domains despite adequate dose and duration (6 weeks or longer) of APD treatment.
•History of symptom instability
•a. \> 3 psychiatric hospitalizations over the last 12 months or 2 over the last 6 months
•Current APD is other than aripiprazole, risperidone, paliperidone, or their LAI versions, ziprasidone, lurasidone, or cariprazine
•Subjects who are diagnosed with schizophreniform disorder or are experiencing their first treated episode of schizophrenia

Arms & Interventions

Drug: KarXT

Intervention: Xanomeline and Trospium Chloride Capsules

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6

Time Frame: Week 6

The PANSS is a medical scale used for measuring symptom severity of participants with schizophrenia. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale. The total score is the sum of all scales with a minimum score of 30 and a maximum score of 210. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.

Secondary Outcomes

Change from Baseline in Personal Social Performance (PSP) at Week 6(Week 6)
Change from Baseline in Clinical Global Impression-Severity (CGI-S) at Week 6(Week 6)
Change from Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Positive symptom factor score at Week 6(Week 6)
Change from Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Negative symptom factor score at Week 6(Week 6)
Categorical response defined as the proportion of subjects achieving a ≥ 30% improvement in PANSS total score at Week 6(Week 6)
Preference of Medication (POM) at Week 6(Week 6)