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

• ClinicalTrials.gov Identifier: NCT04659174
• Recruitment Status: Completed
• First Posted: December 9, 2020
• Last Update Posted: November 29, 2023
• Sponsor: Karuna Therapeutics
• Information provided by (Responsible Party): Karuna Therapeutics

Tracking Information

• First Submitted Date: December 2, 2020
• First Posted Date: December 9, 2020
• Last Update Posted Date: November 29, 2023
• Actual Study Start Date: February 1, 2021
• Actual Primary Completion Date: October 3, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 2, 2020)

Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: From initial dose through 7 days after the final dose (up to 53 weeks) ]

The number and percentage of participants with TEAEs will be determined

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 2, 2020)

• Incidence of serious treatment-emergent adverse events (TEAEs) [ Time Frame: From initial dose through 7 days after the final dose (up to 53 weeks) ]
  The number and percentage of participants with serious TEAEs will be determined
• Incidence of treatment-emergent adverse events (TEAEs) leading to withdrawal [ Time Frame: From initial dose through 7 days after the final dose (up to 53 weeks) ]
  The number and percentage of participants with TEAEs leading to withdrawal will be determined
• Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 52 [ Time Frame: 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.
• Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Score at Week 52 [ Time Frame: 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.
• Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Score at Week 52 [ Time Frame: 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.
• Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Marder Factor Score [ Time Frame: Week 52 ]
  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.
• Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 52 [ Time Frame: 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.
• Percentage of Positive and Negative Syndrome Scale (PANSS) responders (a 30% change in PANSS total score) at Week 52 [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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.

Other Name: KarXT

Study Arms

Experimental: KarXT

Intervention: Drug: Xanomeline and Trospium Chloride Capsules

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 28, 2023): 156
• Original Estimated Enrollment (submitted: December 2, 2020): 350
• Actual Study Completion Date: October 3, 2023
• Actual Primary Completion Date: October 3, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Ukraine, United States

Administrative Information

• NCT Number: NCT04659174
• Other Study ID Numbers: KAR-008
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Karuna Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Karuna Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Inder Kaul, MD; Karuna Therapeutics

• PRS Account: Karuna Therapeutics
• Verification Date: November 2023