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

ClinicalTrials.gov processed this data on November 28, 2023. Link to the current ClinicalTrials.gov record.

Recruitment Status

COMPLETED (See Contacts and Locations)
Verified November 2023 by Karuna Therapeutics

Sponsor

Karuna Therapeutics

Information Provided by (Responsible Party)

Karuna Therapeutics

Clinicaltrials.gov Identifier

NCT04659174
Other Study ID Numbers: KAR-008
First Submitted: December 2, 2020
First Posted: December 9, 2020
Last Update Posted: November 29, 2023
Last Verified: November 2023
History of Changes

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Study Description

Not Provided
Condition or Disease Intervention/Treatment
  • Schizophrenia
  • Drug: Xanomeline and Trospium Chloride Capsules

Study Design

Study TypeInterventional
Actual Enrollment156 participants
Design AllocationN/A
Interventional ModelSingle Group Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleAn Open-label Extension Study to Assess the Long-term Safety, Tolerability, and Efficacy of KarXT in Subjects With DSM-5 Schizophrenia
Study Start DateFebruary 1, 2021
Actual Primary Completion DateOctober 3, 2023
Actual Study Completion DateOctober 3, 2023

Groups and Cohorts

Group/ CohortIntervention/ Treatment
  • 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.

Outcome Measures

Primary Outcome Measures

  1. Incidence of treatment-emergent adverse events (TEAEs) [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) [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 [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 [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 [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 [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 [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 [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 [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.

Eligibility Criteria

Ages Eligible for Study 18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study All
Accepts Healthy Volunteers No
Inclusion Criteria
  • Subject is aged 18 to 65 years, at time of enrollment into the preceding acute study (KAR-007/009).
  • Subject is capable of providing informed consent.
  • A signed informed consent form must be provided before any study assessments are performed.
  • Subject must be fluent in (oral and written) English (United States only) or local language (Ukraine only) to consent.
  • Subject has completed the treatment period on study drug (through Day 35 -2 days) of Studies KAR-007 or KAR-009.
  • Subject resides in a stable living situation, in the opinion of the investigator.
  • 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.
  • 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
  • Risk for suicidal behavior during the study as determined by the investigator's clinical assessment and Columbia-Suicide Severity Rating Scale (C-SSRS).
  • 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.
  • Female subject is pregnant.
  • 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.
  • Subjects with extreme concerns relating to global pandemics such as coronavirus disease 2019 (COVID-19) that preclude study participation.
  • Risk of violent or destructive behavior.
  • Subjects participating in another investigational drug or device trial or planning on participating in another clinical trial during the course of the study.

Contacts and Locations

Sponsors and Collaborators Karuna Therapeutics
Locations
  • Pillar Clinical Research | Bentonville, Arkansas, United States, 72712
  • Woodland International Research Group | Little Rock, Arkansas, United States, 72211
  • Advanced Research Center, Inc. | Anaheim, California, United States, 92805
  • Advanced Research Center Inc | Bellflower, California, United States, 90706
  • CITrials | Bellflower, California, United States, 90706
  • Proscience Research Group | Culver City, California, United States, 90230
  • Collaborative NeuroScience Research, LLC | Garden Grove, California, United States, 92845
  • California Clinical Trial Medical Group | Glendale, California, United States, 91206
  • Synergy San Diego | Lemon Grove, California, United States, 91945
  • CNS Network | Long Beach, California, United States, 90806
  • Catalina Research Institute, LLC | Montclair, California, United States, 91763
  • NRC Research Institute | Orange, California, United States, 92868
  • California Neuropsychopharmacology Clinical Research Institute | Pico Rivera, California, United States, 90660
  • California Neuropsychopharmacology Clinical Research Institute | San Diego, California, United States, 92102
  • Artemis Institute for Clinical Research | San Diego, California, United States, 92103
  • Schuster Medical Research Institute | Sherman Oaks, California, United States, 91403
  • Collaborative Neuroscience Research, LLC. | Torrance, California, United States, 90502
  • Behavioral Clinical Research, Inc. | Hollywood, Florida, United States, 33021
  • Research Centers of America | Hollywood, Florida, United States, 33024
  • Innovative Clinical Research, Inc. | Miami Lakes, Florida, United States, 33016
  • Atlanta Center for Medical Research | Atlanta, Georgia, United States, 30331
  • iResearch Atlanta, LLC | Decatur, Georgia, United States, 30030
  • Mitchell L. Glaser | Chicago, Illinois, United States, 60622
  • Uptown Research Institute | Chicago, Illinois, United States, 60640
  • AMITA Health Center for Psychiatric Research | Hoffman Estates, Illinois, United States, 60169
  • Pillar Clinical Research | Lincolnwood, Illinois, United States, 60712
  • Arch Clinical Trials | Saint Louis, Missouri, United States, 63125
  • Altea Research Institute | Las Vegas, Nevada, United States, 89102
  • Hassman Research Institute | Berlin, New Jersey, United States, 08009
  • Hassman Research Institute | Marlton, New Jersey, United States, 08053
  • Neuro-Behavioral Clinical Research, Inc. | North Canton, Ohio, United States, 44720
  • Community Clinical Research | Austin, Texas, United States, 78754
  • InSite Clinical Research | DeSoto, Texas, United States, 75115
  • Pillar Clinical Research, LLC | Richardson, Texas, United States, 75080
  • Cherkasy Regional Psychiatric Hospital of Cherkasy Regional Council, Female Department #11, Male Department #12 | Smila, Cherkasy Region, Ukraine, 20708
  • Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikov | Dnipro, Ukraine, 49005
  • Institute of Neurology, Psychiatry and Narcology of the National Academy of Medical Sciences of Ukraine | Kharkiv, Ukraine, 61068
  • 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, 73488
  • Kyiv Regional Medical Incorporation "Psychiatry", Center for Novel Treatment and Rehabilitation of Psychotic Disorders | Kyiv, Ukraine, 04080
  • Lviv Regional Clinical Psychiatric Hospital, Department #20 | Lviv, Ukraine, 79021
  • Lviv Regional Clinical Psychiatric Hospital, Department #25 | Lviv, Ukraine, 79021
  • 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, 36013
  • M.I. Pyrogov Vinnytsya National Medical University | Vinnytsya, Ukraine, 21037
Investigators

    More Information

    Additional Relevant MeSH Terms

    • Schizophrenia
    • Schizophrenia Spectrum and Other Psychotic Disorders
    • Mental Disorders