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

Schizophrenia Clinical Trial

Official title:

An Open-label Extension Study to Assess the Long-term Safety, Tolerability, and Efficacy of KarXT in Subjects With DSM-5 Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04659174
• Other study ID #: KAR-008
• Status: Completed
• Phase: Phase 3
• Start date: February 1, 2021
• Est. completion date: October 3, 2023

Study information

• Verified date: November 2023
• Source: Karuna Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 156
• Est. completion date: October 3, 2023
• Est. primary completion date: October 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Xanomeline and Trospium Chloride Capsules
Oral xanomeline 50 mg/trospium 20 mg BID on days 1-2 followed by xanomeline 100 mg/trospium 20 mg BID on days 3-7. The dose is increased to xanomeline 125 mg/trospium 30 mg BID on days 8-364 unless the subject is experiencing adverse events from the xanomeline 100 mg/ trospium 20 mg dose. Subjects who were increased to xanomeline 125 mg/trospium 30 mg will have the option to return to xanomeline 100 mg/ trospium 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.

Locations

Country	Name	City	State
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	Cherkasy Regional Psychiatric Hospital of Cherkasy Regional Council, Female Department #11, Male Department #12	Smila	Cherkasy Region
Ukraine	M.I. Pyrogov Vinnytsya National Medical University	Vinnytsya
United States	Advanced Research Center, Inc.	Anaheim	California
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	Community Clinical Research	Austin	Texas
United States	Advanced Research Center Inc	Bellflower	California
United States	CITrials	Bellflower	California
United States	Pillar Clinical Research	Bentonville	Arkansas
United States	Hassman Research Institute	Berlin	New Jersey
United States	Mitchell L. Glaser	Chicago	Illinois
United States	Uptown Research Institute	Chicago	Illinois
United States	Proscience Research Group	Culver City	California
United States	iResearch Atlanta, LLC	Decatur	Georgia
United States	InSite Clinical Research	DeSoto	Texas
United States	Collaborative NeuroScience Research, LLC	Garden Grove	California
United States	California Clinical Trial Medical Group	Glendale	California
United States	AMITA Health Center for Psychiatric Research	Hoffman Estates	Illinois
United States	Behavioral Clinical Research, Inc.	Hollywood	Florida
United States	Research Centers of America	Hollywood	Florida
United States	Altea Research Institute	Las Vegas	Nevada
United States	Synergy San Diego	Lemon Grove	California
United States	Pillar Clinical Research	Lincolnwood	Illinois
United States	Woodland International Research Group	Little Rock	Arkansas
United States	CNS Network	Long Beach	California
United States	Hassman Research Institute	Marlton	New Jersey
United States	Innovative Clinical Research, Inc.	Miami Lakes	Florida
United States	Catalina Research Institute, LLC	Montclair	California
United States	Neuro-Behavioral Clinical Research, Inc.	North Canton	Ohio
United States	NRC Research Institute	Orange	California
United States	California Neuropsychopharmacology Clinical Research Institute	Pico Rivera	California
United States	Pillar Clinical Research, LLC	Richardson	Texas
United States	Arch Clinical Trials	Saint Louis	Missouri
United States	Artemis Institute for Clinical Research	San Diego	California
United States	California Neuropsychopharmacology Clinical Research Institute	San Diego	California
United States	Schuster Medical Research Institute	Sherman Oaks	California
United States	Collaborative Neuroscience Research, LLC.	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Karuna Therapeutics

Countries where clinical trial is conducted

United States,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events (TEAEs)	The number and percentage of participants with TEAEs will be determined	From initial dose through 7 days after the final dose (up to 53 weeks)
Secondary	Incidence of serious treatment-emergent adverse events (TEAEs)	The number and percentage of participants with serious TEAEs will be determined	From initial dose through 7 days after the final dose (up to 53 weeks)
Secondary	Incidence of treatment-emergent adverse events (TEAEs) leading to withdrawal	The number and percentage of participants with TEAEs leading to withdrawal will be determined	From initial dose through 7 days after the final dose (up to 53 weeks)
Secondary	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 52	The PANSS is a medical scale used for measuring symptom severity of participants with schizophrenia. 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 total score is the sum of all scales with a minimum score of 30 and a maximum score of 210. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.	Week 52
Secondary	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Score at Week 52	The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. For positive symptoms in schizophrenia, participants are rated from 1 to 7 on each symptom scale, with a minimum score of 7 and a maximum score of 49. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.	Week 52
Secondary	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Score at Week 52	The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. For negative symptoms in schizophrenia, participants are rated from 1 to 7 on each symptom scale, with a minimum score of 7 and a maximum score of 49. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.	Week 52
Secondary	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Marder Factor Score	The Negative Marder Factor score is derived from the PANSS and consists of the sum of 5 negative scales (N) and 2 general scales (G) (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), with a minimum score of 7 and a maximum score of 49.	Week 52
Secondary	Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 52	The CGI-S modified asked the clinician 1 question: "Considering your total clinical experience, how mentally ill is the participant at this time?" The clinician's answer rated on the following 7-point scale: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants.	Week 52
Secondary	Percentage of Positive and Negative Syndrome Scale (PANSS) responders (a 30% change in PANSS total score) at Week 52	The PANSS is a medical scale used for measuring symptom severity of participants with schizophrenia. 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 total score is the sum of all scales with a minimum score of 30 and a maximum score of 210. A PANSS responder is defined as a participant with at least a 30% change in PANSS total score compared to baseline at Week 52.	Week 52