An Extension Study to Assess Long-term Safety, Tolerability, and Efficacy of KarXT in Adult Patients With Schizophrenia (EMERGENT-4)

NCT ID: NCT04659174

Last Updated: 2024-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 152 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-01
• Study Completion Date: 2023-10-03

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.

Conditions

Schizophrenia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

KarXT

Group Type: EXPERIMENTAL

Xanomeline and Trospium Chloride Capsules

Intervention Type: DRUG

Oral xanomeline 50 mg/trospium chloride 20 mg BID on days 1-2 followed by xanomeline 100 mg/trospium chloride 20 mg BID on days 3-7. The dosage is increased to xanomeline 125 mg/trospium chloride 30 mg BID on days 8-364 unless the subject is experiencing adverse events from the xanomeline 100 mg/ trospium chloride 20 mg dose. Subjects who were increased to xanomeline 125 mg/trospium chloride 30 mg will have the option to return to xanomeline 100 mg/ trospium chloride 20 mg depending on clinical response and tolerability. Re-escalation to 125/30 BID or re-titration in cases in which the subject has been off KarXT for a longer period of time (at least a week) is allowed and will require a discussion between the principal investigator and the medical monitor.

Interventions

Xanomeline and Trospium Chloride Capsules

Oral xanomeline 50 mg/trospium chloride 20 mg BID on days 1-2 followed by xanomeline 100 mg/trospium chloride 20 mg BID on days 3-7. The dosage is increased to xanomeline 125 mg/trospium chloride 30 mg BID on days 8-364 unless the subject is experiencing adverse events from the xanomeline 100 mg/ trospium chloride 20 mg dose. Subjects who were increased to xanomeline 125 mg/trospium chloride 30 mg will have the option to return to xanomeline 100 mg/ trospium chloride 20 mg depending on clinical response and tolerability. Re-escalation to 125/30 BID or re-titration in cases in which the subject has been off KarXT for a longer period of time (at least a week) is allowed and will require a discussion between the principal investigator and the medical monitor.

Intervention Type: DRUG

Other Intervention Names

KarXT

Eligibility Criteria

Inclusion Criteria

1. Subject is aged 18 to 65 years, at time of enrollment into the preceding acute study (KAR-007/009).

2. Subject is capable of providing informed consent.

1. A signed informed consent form must be provided before any study assessments are performed.

2. Subject must be fluent in (oral and written) English (United States only) or local language (Ukraine only) to consent.

3. Subject has completed the treatment period on study drug (through Day 35 -2 days) of Studies KAR-007 or KAR-009.

4. Subject resides in a stable living situation, in the opinion of the investigator.

5. 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.

6. 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

1. Risk for suicidal behavior during the study as determined by the investigator's clinical assessment and Columbia-Suicide Severity Rating Scale (C-SSRS).

2. 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.

3. Female subject is pregnant.

4. 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.

5. Subjects with extreme concerns relating to global pandemics such as coronavirus disease 2019 (COVID-19) that preclude study participation.

6. Risk of violent or destructive behavior.

7. Subjects participating in another investigational drug or device trial or planning on participating in another clinical trial during the course of the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karuna Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Pillar Clinical Research

Bentonville, Arkansas, United States

Woodland International Research Group

Little Rock, Arkansas, United States

Advanced Research Center, Inc.

Anaheim, California, United States

Advanced Research Center Inc

Bellflower, California, United States

CITrials

Bellflower, California, United States

Proscience Research Group

Culver City, California, United States

Collaborative NeuroScience Research, LLC

Garden Grove, California, United States

California Clinical Trial Medical Group

Glendale, California, United States

Synergy San Diego

Lemon Grove, California, United States

CNS Network

Long Beach, California, United States

Catalina Research Institute, LLC

Montclair, California, United States

NRC Research Institute

Orange, California, United States

California Neuropsychopharmacology Clinical Research Institute

Pico Rivera, California, United States

California Neuropsychopharmacology Clinical Research Institute

San Diego, California, United States

Artemis Institute for Clinical Research

San Diego, California, United States

Schuster Medical Research Institute

Sherman Oaks, California, United States

Collaborative Neuroscience Research, LLC.

Torrance, California, United States

Behavioral Clinical Research, Inc.

Hollywood, Florida, United States

Research Centers of America

Hollywood, Florida, United States

Innovative Clinical Research, Inc.

Miami Lakes, Florida, United States

Atlanta Center for Medical Research

Atlanta, Georgia, United States

iResearch Atlanta, LLC

Decatur, Georgia, United States

Mitchell L. Glaser

Chicago, Illinois, United States

Uptown Research Institute

Chicago, Illinois, United States

AMITA Health Center for Psychiatric Research

Hoffman Estates, Illinois, United States

Pillar Clinical Research

Lincolnwood, Illinois, United States

Arch Clinical Trials

St Louis, Missouri, United States

Altea Research Institute

Las Vegas, Nevada, United States

Hassman Research Institute

Berlin, New Jersey, United States

Hassman Research Institute

Marlton, New Jersey, United States

Neuro-Behavioral Clinical Research, Inc.

North Canton, Ohio, United States

Community Clinical Research

Austin, Texas, United States

InSite Clinical Research

DeSoto, Texas, United States

Pillar Clinical Research, LLC

Richardson, Texas, United States

Cherkasy Regional Psychiatric Hospital of Cherkasy Regional Council, Female Department #11, Male Department #12

Smila, Cherkasy Oblast, Ukraine

Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikov

Dnipro, , Ukraine

Institute of Neurology, Psychiatry and Narcology of the National Academy of Medical Sciences of Ukraine

Kharkiv, , Ukraine

Regional Clinical Psychiatric Hospital No. 3, Adult Psychiatric Department No. 3

Kharkiv, , Ukraine

Kherson Regional Insititution of Mental Care of Kherson Regional Council Male Psychiatric Department #3, Femail Psychiatric Department #10

Kherson, , Ukraine

Kyiv Regional Medical Incorporation "Psychiatry", Center for Novel Treatment and Rehabilitation of Psychotic Disorders

Kyiv, , Ukraine

Lviv Regional Clinical Psychiatric Hospital, Department #20

Lviv, , Ukraine

Lviv Regional Clinical Psychiatric Hospital, Department #25

Lviv, , Ukraine

Regional Facility for Psychiatric Care of Poltava Regional Council, 2-A acute general psychiatric male ward, 5-B acute, quiet, general psychiatric female ward, Poltava State Medical University, Academic Department of Psychiatry, Addictology and Medical

Poltava, , Ukraine

M.I. Pyrogov Vinnytsya National Medical University

Vinnytsia, , Ukraine

Countries

United States; Ukraine

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

KAR-008

Identifier Type: -

Identifier Source: org_study_id