Clinical trial NCT04659174: An Extension Study to Assess Long-term Safety, Tolerability, and Efficacy of KarXT in Adult Patients With Schizophrenia (EMERGENT-4)
Official title: An Open-label Extension Study to Assess the Long-term Safety, Tolerability, and Efficacy of KarXT in Subjects With DSM-5 Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Lead sponsor: Karuna Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-12-09
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose to end of study (Up to approximately 53 weeks)
Secondary outcomes:
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From first dose to end of study (Up to approximately 53 weeks)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAE) Leading to Study Drug Discontinuation
timeFrame: From first dose to end of study (Up to approximately 53 weeks)
measure: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 52
timeFrame: Open-label extension baseline, week 52
measure: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Score at Week 52
timeFrame: Open-labe extension baseline, week 52
measure: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Score at Week 52
timeFrame: Open-label extension baseline, week 52
measure: Change From Baseline in PANSS Negative Marder Factor Score at Week 52
timeFrame: Open-label extension baseline, week 52
measure: Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 52
timeFrame: Open-label extension baseline, week 52
measure: Percentage of PANSS Responders With >=30% Reduction in PANSS Total Score at Week 52
timeFrame: At week 52
Other outcomes:
Locations:
city: Bentonville
country: United States
facility: Pillar Clinical Research
state: Arkansas
city: Little Rock
country: United States
facility: Woodland International Research Group
state: Arkansas
city: Anaheim
country: United States
facility: Advanced Research Center, Inc.
state: California
city: Bellflower
country: United States
facility: Advanced Research Center Inc
state: California
city: Bellflower
country: United States
facility: CITrials
state: California
city: Culver City
country: United States
facility: Proscience Research Group
state: California
city: Garden Grove
country: United States
facility: Collaborative NeuroScience Research, LLC
state: California
city: Glendale
country: United States
facility: California Clinical Trial Medical Group
state: California
city: Lemon Grove
country: United States
facility: Synergy San Diego
state: California
city: Long Beach
country: United States
facility: CNS Network
state: California
city: Montclair
country: United States
facility: Catalina Research Institute, LLC
state: California
city: Orange
country: United States
facility: NRC Research Institute
state: California
city: Pico Rivera
country: United States
facility: California Neuropsychopharmacology Clinical Research Institute
state: California
city: San Diego
country: United States
facility: California Neuropsychopharmacology Clinical Research Institute
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Sherman Oaks
country: United States
facility: Schuster Medical Research Institute
state: California
city: Torrance
country: United States
facility: Collaborative Neuroscience Research, LLC.
state: California
city: Hollywood
country: United States
facility: Behavioral Clinical Research, Inc.
state: Florida
city: Hollywood
country: United States
facility: Research Centers of America
state: Florida
city: Miami Lakes
country: United States
facility: Innovative Clinical Research, Inc.
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Decatur
country: United States
facility: iResearch Atlanta, LLC
state: Georgia
city: Chicago
country: United States
facility: Mitchell L. Glaser
state: Illinois
city: Chicago
country: United States
facility: Uptown Research Institute
state: Illinois
city: Hoffman Estates
country: United States
facility: AMITA Health Center for Psychiatric Research
state: Illinois
city: Lincolnwood
country: United States
facility: Pillar Clinical Research
state: Illinois
city: Saint Louis
country: United States
facility: Arch Clinical Trials
state: Missouri
city: Las Vegas
country: United States
facility: Altea Research Institute
state: Nevada
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: Marlton
country: United States
facility: Hassman Research Institute
state: New Jersey
city: North Canton
country: United States
facility: Neuro-Behavioral Clinical Research, Inc.
state: Ohio
city: Austin
country: United States
facility: Community Clinical Research
state: Texas
city: DeSoto
country: United States
facility: InSite Clinical Research
state: Texas
city: Richardson
country: United States
facility: Pillar Clinical Research, LLC
state: Texas
city: Smila
country: Ukraine
facility: Cherkasy Regional Psychiatric Hospital of Cherkasy Regional Council, Female Department #11, Male Department #12
state: Cherkasy Region
city: Dnipro
country: Ukraine
facility: Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikov
city: Kharkiv
country: Ukraine
facility: Institute of Neurology, Psychiatry and Narcology of the National Academy of Medical Sciences of Ukraine
city: Kharkiv
country: Ukraine
facility: Regional Clinical Psychiatric Hospital No. 3, Adult Psychiatric Department No. 3
city: Kherson
country: Ukraine
facility: Kherson Regional Insititution of Mental Care of Kherson Regional Council Male Psychiatric Department #3, Femail Psychiatric Department #10
city: Kyiv
country: Ukraine
facility: Kyiv Regional Medical Incorporation "Psychiatry", Center for Novel Treatment and Rehabilitation of Psychotic Disorders
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Psychiatric Hospital, Department #20
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Psychiatric Hospital, Department #25
city: Poltava
country: Ukraine
facility: 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
city: Vinnytsya
country: Ukraine
facility: M.I. Pyrogov Vinnytsya National Medical University
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: