An Open-label Study to Assess the Long-term Safety, Tolerability, and Efficacy of KarXT in De Novo Subjects With DSM-5 Schizophrenia

Karuna Therapeutics114 sites in 1 country566 target enrollmentJune 2, 2021

ConditionsSchizophrenia

InterventionsXanomeline and Trospium Chloride Capsules

DrugsXanomeline and Trospium Chloride Capsules

Overview

Phase: Phase 3
Intervention: Xanomeline and Trospium Chloride Capsules
Conditions: Schizophrenia
Sponsor: Karuna Therapeutics
Enrollment: 566
Locations: 114
Primary Endpoint: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Status: Completed
Last Updated: 7 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase 3, multicenter, 56-week, outpatient, open-label (OL) study to evaluate the long-term safety, tolerability, and efficacy of KarXT in de novo subjects with Diagnostic and Statistical Manual-Fifth Edition (DSM-5) schizophrenia. In this OL study, all subjects will receive KarXT (a fixed combination of xanomeline 125 mg and trospium chloride 30 mg twice daily [BID]) for up to 52 weeks. The primary objective of the study is to assess the long-term safety and tolerability of KarXT in subjects with a DSM-5 diagnosis of schizophrenia. The secondary objective of this study is to assess the long-term efficacy and characterize the pharmacokinetics of xanomeline and trospium after administration of KarXT.

Registry

clinicaltrials.gov

Start Date

June 2, 2021

End Date

May 24, 2024

Last Updated

7 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Karuna Therapeutics

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subject is aged 18 to 65 years at screening.
•Subject is capable of providing informed consent.
•A signed informed consent form (ICF) must be provided before any study assessments are performed.
•Subject must be fluent in (oral and written) the language of the ICGF to consent.
•Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 (American Psychiatric Association 2013) criteria and confirmed by Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorder Studies (MINI) version 7.0.
•Subject has not required psychiatric hospitalization, acute crisis intervention, or other increase in level of care due to symptom exacerbation within 8 weeks of screening and is psychiatrically stable in the opinion of the investigator.
•PANSS total score ≤ 80 at screening and Baseline Visit B (Day 0).
•Clinical Global Impression - Severity (CGI-S) score of ≤ 4 at screening and Baseline Visit B (Day 0).
•At the time of screening, or at any time within the 30 days prior to screening, the subject must have received an oral antipsychotic medication daily at a dose and frequency consistent with the drug label.
•In the opinion of the investigator, it is clinically appropriate for the subject to discontinue current antipsychotic therapy and initiate experimental treatment with KarXT.

Exclusion Criteria

•Any primary DSM-5 disorder other than schizophrenia within 12 months before screening (confirmed using MINI version 7.0.2 at screening).
•Subject has a history of moderate to severe alcohol use disorder or a substance (other than nicotine or caffeine) use disorder within the past 12 months or a positive urine drug screen (UDS) for a substance other than cannabis at screening or baseline.
•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
•Subject has 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 Columbia-Suicide Severity Rating Scale (C-SSRS).
•Clinically significant abnormal finding from the physical examination, medical history, ECG, or clinical laboratory results at screening.
•Subjects cannot currently (within 5 half-lives before Day 0) be receiving monoamine oxidase inhibitors, anticonvulsants, tricyclic antidepressants, centrally active anticholinergics, or any other psychoactive medications other than daily antipsychotic maintenance therapy. As-needed anxiolytics and/or sleep aids are permitted. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors taken at stable dose may be permitted.
•Subject has a history of treatment resistance to schizophrenia medications defined as failure to respond to 2 adequate courses of pharmacotherapy (a minimum of 4 weeks at an adequate dose per the label) within the past 12 months or having received clozapine within the past 3 years

Arms & Interventions

KarXT

Intervention: Xanomeline and Trospium Chloride Capsules

Outcomes

Primary Outcomes

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

Time Frame: From time of consent to end of study (approximately 400 days)

TEAEs are defined as events with an onset date on or after the first dose of KarXT. An Adverse Event is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at baseline, worsens during the study, regardless of the suspected cause of the event using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

Secondary Outcomes

Number of Participants With Serious Treatment Emergent Adverse Events (STEAEs)(From time of consent to end of study (approximately 400 days))
Number of Participants With TEAE Leading to Study Drug Discontinuation(From time of consent to end of study (approximately 400 days))
Change From Baseline in PANSS Total Score at Week 52(At baseline and week 52)
Change From Baseline in PANSS Positive Score at Week 52(At baseline and week 52)
Change From Baseline in PANSS Negative Score at Week 52(At baseline and week 52)
Change From Baseline in PANSS Marder Factor Negative Score at Week 52(At baseline and week 52)
Change From Baseline in Clinical Global Impressions-severity (CGI-S) Score Week 52(At baseline and week 52)
Percentage of Participants With a ≥30% Reduction in PANSS Total Score at Week 52(At baseline and week 52)
Number of Participants With Adverse Events of Special Interest (AESI)(From time of consent to end of study (approximately 400 days))
Number of Participants With Anticholinergic and Procholinergic Symptoms(From time of consent to end of study (approximately 400 days))
Change From Baseline in Simpson-Angus Rating Scale (SAS)(From time of consent to end of study (approximately 400 days))
Change From Baseline in Barnes Akathisia Rating Scale (BARS)(From time of consent to end of study (approximately 400 days))
Change From Baseline in Total Abnormal Involuntary Movement Scale (AIMS)(From time of consent to end of study (approximately 400 days))
Change From Baseline in Body Mass Index (BMI)(From time of consent to end of study (approximately 400 days))
Change From Baseline in Waist Circumference(From time of consent to end of study (approximately 400 days))
Change From Baseline in Blood Pressure Values(From time of consent to end of study (approximately 400 days))
Change From Baseline in Heart Rate(From time of consent to end of study (approximately 400 days))
Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments(From time of consent to end of study (approximately 400 days))
Number of Participants With Clinically Significant Changes in 12 Lead Electrocardiogram(From time of consent to end of study (approximately 400 days))
Number of Participants With Clinically Significant Changes in Physical Examination(From time of consent to end of study (approximately 400 days))
Number of Participants With Suicidal Ideation Based on the Columbia Suicide Severity Rating Scale (C-SSRS)(From time of consent to end of study (approximately 400 days))