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

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ClinicalTrials.gov Identifier: NCT04659174
Recruitment Status : Recruiting
First Posted : December 9, 2020
Last Update Posted : January 27, 2021
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: Xanomeline and Trospium Chloride Capsules Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 350 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Extension Study to Assess the Long-term Safety, Tolerability, and Efficacy of KarXT in Subjects With DSM-5 Schizophrenia
Estimated Study Start Date : January 2021
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arm Intervention/treatment
Experimental: KarXT 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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04659174


Contacts
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Contact: Stephen Brannan, MD 857-449-2234 sbrannan@karunatx.com

Locations
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United States, California
Synergy San Diego Recruiting
Lemon Grove, California, United States, 91945
United States, Florida
Innovative Clinical Research, Inc. Recruiting
Miami Lakes, Florida, United States, 33016
United States, Georgia
iResearch Atlanta, LLC Recruiting
Decatur, Georgia, United States, 30030
United States, Illinois
Pillar Clinical Research Recruiting
Lincolnwood, Illinois, United States, 60712
United States, Nevada
Altea Research Institute Recruiting
Las Vegas, Nevada, United States, 89102
United States, New Jersey
Hassman Research Institute Recruiting
Marlton, New Jersey, United States, 08053
United States, Texas
Pillar Clinical Research, LLC Recruiting
Richardson, Texas, United States, 75080
Sponsors and Collaborators
Karuna Therapeutics
Investigators
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Study Director: Inder Kaul, MD Karuna Therapeutics
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Responsible Party: Karuna Therapeutics
ClinicalTrials.gov Identifier: NCT04659174    
Other Study ID Numbers: KAR-008
First Posted: December 9, 2020    Key Record Dates
Last Update Posted: January 27, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Xanomeline
Trospium chloride
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Urological Agents
Parasympathomimetics
Psychotropic Drugs
Muscarinic Agonists
Cholinergic Agonists