An Open-label Extension Study to Assess the Long-term Safety, Tolerability, and Efficacy of KarXT in Subjects With DSM-5 Schizophrenia
Overview
- Phase
- Phase 3
- Intervention
- Xanomeline and Trospium Chloride Capsules
- Conditions
- Schizophrenia
- Sponsor
- Karuna Therapeutics
- Enrollment
- 152
- Locations
- 41
- Primary Endpoint
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a Phase 3, multicenter, 53-week, outpatient, open-label extension (OLE) study to evaluate the long-term safety, tolerability, and efficacy of KarXT in subjects with Diagnostic and Statistical Manual-Fifth Edition (DSM-5) schizophrenia who previously completed the treatment period of one of the two Phase 3 double-blind studies, KAR-007 or KAR-009. In this OLE 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 regardless of treatment assignment in the preceding Phase 3 acute study. 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 monitor trough concentrations of xanomeline and trospium after administration of KarXT.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject is aged 18 to 65 years, at time of enrollment into the preceding acute study (KAR-007/009).
- •Subject is capable of providing informed consent.
- •A signed informed consent form must be provided before any study assessments are performed.
- •Subject must be fluent in (oral and written) English (United States only) or local language (Ukraine only) to consent.
- •Subject has completed the treatment period on study drug (through Day 35 -2 days) of Studies KAR-007 or KAR-
- •Subject resides in a stable living situation, in the opinion of the investigator.
- •Subject has an identified, reliable informant/caregiver willing to be able to address some questions related to certain study visits, if needed. An informant/caregiver may not be necessary if the subject has been the patient of the investigator for ≥1 year.
- •Women of childbearing potential or men with sexual partners of childbearing potential must be sexually abstinent (in line with their preferred and usual lifestyle) or willing and able to use at least 1 highly effective method of contraception during the study and for at least 7 days after the last dose of KarXT. Sperm donation is not allowed for 7 days after the final dose of KarXT.
Exclusion Criteria
- •Risk for suicidal behavior during the study as determined by the investigator's clinical assessment and Columbia-Suicide Severity Rating Scale (C-SSRS).
- •Any clinically significant abnormality, including any finding(s) from the physical examination, vital signs, ECG, or laboratory test at the end-of-treatment visit of Studies KAR-007 or KAR-009 that the investigator, in consultation with the medical monitor, would consider to jeopardize the safety of the subject.
- •Female subject is pregnant.
- •If, in the opinion of the investigator (and/or Sponsor), subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the investigator (and/or Sponsor), may compromise the safety of the subject or affect his/her ability to adhere to the protocol visit schedule or fulfill visit requirements.
- •Subjects with extreme concerns relating to global pandemics such as coronavirus disease 2019 (COVID-19) that preclude study participation.
- •Risk of violent or destructive behavior.
- •Subjects participating in another investigational drug or device trial or planning on participating in another clinical trial during the course of the study.
Arms & Interventions
KarXT
Intervention: Xanomeline and Trospium Chloride Capsules
Outcomes
Primary Outcomes
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: From first dose to end of study (Up to approximately 53 weeks)
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 Adverse Events (SAEs)(From first dose to end of study (Up to approximately 53 weeks))
- Number of Participants With Treatment-Emergent Adverse Events (TEAE) Leading to Study Drug Discontinuation(From first dose to end of study (Up to approximately 53 weeks))
- Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 52(Open-label extension baseline, week 52)
- Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Score at Week 52(Open-labe extension baseline, week 52)
- Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Score at Week 52(Open-label extension baseline, week 52)
- Change From Baseline in PANSS Negative Marder Factor Score at Week 52(Open-label extension baseline, week 52)
- Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 52(Open-label extension baseline, week 52)
- Percentage of PANSS Responders With >=30% Reduction in PANSS Total Score at Week 52(At week 52)