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

Phase 3

Completed

• Conditions: Schizophrenia
• Interventions: Drug: Xanomeline and Trospium Chloride Capsules

• Registration Number: NCT04659174
• Lead Sponsor: Karuna Therapeutics

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-12-02
• Study First Submitted QC: 2020-12-02
• Study First Posted: 2020-12-09
• Study Start: 2021-02-01
• Primary Completion: 2023-10-03
• Study Completion: 2023-10-03
• Status Verified: 2024-10
• Results First Submitted: 2024-10-02
• Results First Submitted QC: 2024-10-02
• Last Update Submitted: 2024-10-02
• Results First Posted: 2024-10-28
• Last Update Posted: 2024-10-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 152

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
KarXT	Xanomeline and Trospium Chloride Capsules	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	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 Outcome Measures

Name	Time	Method
Number of Participants With Serious Adverse Events (SAEs)	From first dose to end of study (Up to approximately 53 weeks)	An SAE is any untoward medical occurrence, in the view of either the investigator or sponsor, that results in death; is life-threatening; results in inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity, and/or; is a congenital anomaly/birth defect using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
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)	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.
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 52	Open-label extension baseline, week 52	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 positive symptoms in schizophrenia are the excess or distortion of normal function and the negative symptoms are the diminution or loss of normal functions. PANSS total score is the sum of all 30 items with a minimum score of 30 and a maximum score of 210. Higher scores indicate more severe symptoms. Open-label Extension Baseline (OLEB) is defined as the most recent measurement prior to the first administration of study drug in KAR-008. The assessments performed on Visit 10 (Day 35) of studies KAR-007 or KAR-009 will be considered for OLEB baseline along with any additional procedures that will be performed on Day 0 of KAR-008.
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Score at Week 52	Open-labe extension baseline, week 52	PANSS positive score is the sum of all PANSS 7 positive symptom scales with a minimum score of 7 and a maximum score of 49. Higher scores indicate more severe symptoms. Participants are rated from 1 to 7 on each symptom scale. The positive symptoms in schizophrenia are the excess or distortion of normal function such as hallucinations, delusions, grandiosity, and hostility. Open-label Extension Baseline (OLEB) is defined as the most recent measurement prior to the first administration of study drug in KAR-008. The assessments performed on Visit 10 (Day 35) of studies KAR-007 or KAR-009 will be considered for OLEB baseline along with any additional procedures that will be performed on Day 0 of KAR-008.
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Score at Week 52	Open-label extension baseline, week 52	PANSS negative score is the sum of all PANSS 7 negative symptom scales with a minimum score of 7 and a maximum score of 49. Higher scores indicate more severe symptoms. Participants are rated from 1 to 7 on each symptom scale. The negative symptoms in schizophrenia are the diminution or loss of normal functions. Open-label Extension Baseline (OLEB) is defined as the most recent measurement prior to the first administration of study drug in KAR-008. The assessments performed on Visit 10 (Day 35) of studies KAR-007 or KAR-009 will be considered for OLEB baseline along with any additional procedures that will be performed on Day 0 of KAR-008.
Change From Baseline in PANSS Negative Marder Factor Score at Week 52	Open-label extension baseline, week 52	PANSS Negative Marder Factor Score is the sum of 5 negative scales and 2 general scales (N1. Blunted affect; N2. Emotional withdrawal; N3. Poor rapport; N4. Passive/apathetic social withdrawal; N6. Lack of spontaneity; G7. Motor retardation; and G16. Active social avoidance). Participants are rated from 1 to 7 on each symptom scale. Higher score indicates more severe symptoms. The negative symptoms in schizophrenia are the diminution or loss of normal functions. Open-label Extension Baseline (OLEB) is defined as the most recent measurement prior to the first administration of study drug in KAR-008. The assessments performed on Visit 10 (Day 35) of studies KAR-007 or KAR-009 will be considered for OLEB baseline along with any additional procedures that will be performed on Day 0 of KAR-008.
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 52	Open-label extension baseline, week 52	Completed independently by a clinician, the CGI-S categorizes the severity of the illness as: 1 = Normal, not at all ill; 2 = Borderline mentally ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; and 7 = Among the most extremely ill patients, by asking the clinical 1 question and providing a rating based upon observed and reported symptoms, behavior, and function in the past 7 days to reflect the average severity level across the 7 days. Higher score indicates more severe illness. Open-label Extension Baseline (OLEB) is defined as the most recent measurement prior to the first administration of study drug in KAR-008. The assessments performed on Visit 10 (Day 35) of studies KAR-007 or KAR-009 will be considered for OLEB baseline along with any additional procedures that will be performed on Day 0 of KAR-008.
Percentage of PANSS Responders With >=30% Reduction in PANSS Total Score at Week 52	At week 52	A PANSS responder is defined as a participant with reduction from open-label extension baseline (OLEB) of at least a 30% improvement at Week 52 in the PANSS total score. 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. PANSS total score is the sum of all 30 items with a minimum score of 30 and a maximum score of 210. Higher scores indicate more severe symptoms. OLEB is defined as the most recent measurement prior to the first administration of study drug in KAR-008. The assessments performed on Visit 10 (Day 35) of studies KAR-007 or KAR-009 will be considered for OLEB baseline along with any additional procedures that will be performed on Day 0 of KAR-008.

Trial Locations

Locations (41)

Pillar Clinical Research; 🇺🇸 Lincolnwood, Illinois, United States

iResearch Atlanta, LLC; 🇺🇸 Decatur, Georgia, United States

Artemis Institute for Clinical Research; 🇺🇸 San Diego, California, United States

Atlanta Center for Medical Research; 🇺🇸 Atlanta, Georgia, United States

Cherkasy Regional Psychiatric Hospital of Cherkasy Regional Council, Female Department #11, Male Department #12; 🇺🇦 Smila, Cherkasy Region, Ukraine

Woodland International Research Group; 🇺🇸 Little Rock, Arkansas, United States

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; 🇺🇦 Vinnytsya, Ukraine

InSite Clinical Research; 🇺🇸 DeSoto, Texas, United States

Neuro-Behavioral Clinical Research, Inc.; 🇺🇸 North Canton, Ohio, United States

Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikov; 🇺🇦 Dnipro, Ukraine

Proscience Research Group; 🇺🇸 Culver City, California, United States

Uptown Research Institute; 🇺🇸 Chicago, Illinois, United States

AMITA Health Center for Psychiatric Research; 🇺🇸 Hoffman Estates, Illinois, United States

Altea Research Institute; 🇺🇸 Las Vegas, Nevada, United States

Arch Clinical Trials; 🇺🇸 Saint Louis, Missouri, United States

Hassman Research Institute; 🇺🇸 Marlton, New Jersey, United States

Lviv Regional Clinical Psychiatric Hospital, Department #20; 🇺🇦 Lviv, Ukraine

Community Clinical Research; 🇺🇸 Austin, Texas, United States

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

Pillar Clinical Research, LLC; 🇺🇸 Richardson, Texas, United States

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

Lviv Regional Clinical Psychiatric Hospital, Department #25; 🇺🇦 Lviv, Ukraine

Mitchell L. Glaser; 🇺🇸 Chicago, Illinois, United States

Advanced Research Center, Inc.; 🇺🇸 Anaheim, California, United States

Advanced Research Center Inc; 🇺🇸 Bellflower, California, United States

CITrials; 🇺🇸 Bellflower, California, United States

NRC Research Institute; 🇺🇸 Orange, California, United States

Collaborative NeuroScience Research, LLC; 🇺🇸 Garden Grove, California, United States

Catalina Research Institute, LLC; 🇺🇸 Montclair, California, United States

CNS Network; 🇺🇸 Long Beach, California, United States

California Clinical Trial Medical Group; 🇺🇸 Glendale, California, United States

Synergy San Diego; 🇺🇸 Lemon Grove, California, United States

Schuster Medical Research Institute; 🇺🇸 Sherman Oaks, California, United States

California Neuropsychopharmacology Clinical Research Institute; 🇺🇸 San Diego, California, United States

Collaborative Neuroscience Research, LLC.; 🇺🇸 Torrance, California, United States

Research Centers of America; 🇺🇸 Hollywood, Florida, United States

Innovative Clinical Research, Inc.; 🇺🇸 Miami Lakes, Florida, United States

Behavioral Clinical Research, Inc.; 🇺🇸 Hollywood, Florida, United States

Institute of Neurology, Psychiatry and Narcology of the National Academy of Medical Sciences of Ukraine; 🇺🇦 Kharkiv, Ukraine