An Extension Study to Assess Long-Term Safety and Tolerability of Adjunctive KarXT in Subjects With Inadequately Controlled Symptoms of Schizophrenia

Study Overview
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Brief Summary
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This is a Phase 3, multicenter, 52-week, outpatient, open-label extension (OLE) study to evaluate the long-term safety and tolerability of adjunctive KarXT in subjects with schizophrenia with an inadequate response to their current antipsychotic treatment who previously completed the treatment period (Visit 8/Day 42 ± 3) of ARISE Study (KAR-012). The primary objective of the study is to assess the long-term safety and tolerability of adjunctive KarXT (a fixed dose combination of xanomeline and trospium chloride twice daily [BID]) in subjects with schizophrenia. Additional exploratory objectives assess the efficacy of adjunctive KarXT at scheduled visits.

Official Title
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An Open-label Extension Study to Assess the Long-term Safety and Tolerability of Adjunctive KarXT in Subjects With Inadequately Controlled Symptoms of Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Xanomeline and Trospium Chloride Capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is aged ≥18 to <60 years at the time of randomization of Study KAR-012 Subject has successfully completed the treatment period of ARISE Study (KAR-012) Subject has been compliant with the procedures in ARISE Study (KAR-012) (in the Principal Investigator's judgement) Subject has been compliant with their background antipsychotic drug in Study KAR-012 in the opinion of the Investigator and based on subject and informant reporting Subject is capable of providing signed Informed Consent Form before any study assessments will be performed Subject resides in a stable living situation, in the opinion of the Investigator Subject has identified a reliable informant/caregiver willing and able to assist with study activities as needed throughout the subject's participation in the study. The informant can complete the study visits assessments via phone (as per local regulations). In Bulgaria, the informant must be physically present at all study visits. Women of childbearing potential (WOCP), or men whose sexual partners are WOCP, must be able and willing to use at least 1 highly effective method of contraception during the study and for at least 1 menstrual cycle (e.g., 30 days) after the last dose of study drug. Sperm donation is not allowed for 30 days after the final dose of the study drug. A female subject is considered to be a WOCP after menarche and until she is in a postmenopausal state for 12 months or otherwise permanently sterile (for which acceptable methods include hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). Exclusion Criteria: Risk for suicidal behavior during the study as determined by the Investigator's clinical assessment and/or Columbia-Suicide Severity Rating Scale (C-SSRS) as confirmed by the following: Subject answers Yes to suicidal ideation Item 4 (active suicidal ideation with some intent to act, without a specific plan) or Item 5 (active suicidal ideation with a specific plan and intent) on the C-SSRS Non-suicidal self-injurious behavior is not exclusionary Any clinically significant abnormalities, including any finding(s) from ECG, or laboratory test at Visit 6, and the physical examination, vital signs, at the EOT visit of ARISE Study KAR-012 that the Investigator, in consultation with the Medical Monitor are considered to jeopardize the safety of the subject Female subject is pregnant If, in the opinion of the Investigator (and/or Sponsor/ Medical Monitor), subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the Investigator (and/or Sponsor /Medical Monitor), may compromise the safety of the subject or affect their ability to adhere to the protocol visit schedule or study requirements Risk of violent or destructive behavior as per Investigator's judgement Subjects participating in another investigational drug or device trial or planning on participating in another clinical trial during the study History or high risk of urinary retention, gastric retention, or narrow angle glaucoma as evaluated by the Investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug: KarXT<br> | Drug: Xanomeline and Trospium Chloride Capsules<br>* KarXT 50 mg/20 mg BID KarXT 75mg/20 mg BID KarXT 100mg/20 mg BID KarXT 125mg/30 mg BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs) |  | From initial dose to safety follow-up visit (54 weeks) or early termination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of serious treatment-emergent adverse events (TEAEs) |  | From initial dose to safety follow-up visit (54 weeks) or early termination | 
| Incidence of TEAEs leading to discontinuation of study drug |  | From initial dose to safety follow-up visit (54 weeks) or early termination |