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 October 2, 2024. Link to the current ClinicalTrials.gov record.

Recruitment Status

COMPLETED - HAS RESULTS
 (See Contacts and Locations)
Verified October 2024 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
Results First Posted: October 28, 2024
Last Update Posted: October 28, 2024
Last Verified: October 2024
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 Enrollment152 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 chloride 20 mg BID on days 1-2 followed by xanomeline 100 mg/trospium chloride 20 mg BID on days 3-7. The dosage is increased to xanomeline 125 mg/trospium chloride 30 mg BID on days 8-364 unless the subject is experiencing adverse events from the xanomeline 100 mg/ trospium chloride 20 mg dose. Subjects who were increased to xanomeline 125 mg/trospium chloride 30 mg will have the option to return to xanomeline 100 mg/ trospium chloride 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. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [From first dose to end of study (Up to approximately 53 weeks)]
    TEAEs are defined as events with an onset date on or after the first dose of KarXT. An Adverse Event is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at baseline, worsens during the study, regardless of the suspected cause of the event using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

Secondary Outcome Measures

  1. Number of Participants With Serious Adverse Events (SAEs) [From first dose to end of study (Up to approximately 53 weeks)]
    An SAE is any untoward medical occurrence, in the view of either the investigator or sponsor, that results in death; is life-threatening; results in inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity, and/or; is a congenital anomaly/birth defect using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
  2. Number of Participants With Treatment-Emergent Adverse Events (TEAE) Leading to Study Drug Discontinuation [From first dose to end of study (Up to approximately 53 weeks)]
    TEAEs are defined as events with an onset date on or after the first dose of KarXT. An Adverse Event is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at baseline, worsens during the study, regardless of the suspected cause of the event using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
  3. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 52 [Open-label extension baseline, week 52]
    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 positive symptoms in schizophrenia are the excess or distortion of normal function and the negative symptoms are the diminution or loss of normal functions. PANSS total score is the sum of all 30 items with a minimum score of 30 and a maximum score of 210. Higher scores indicate more severe symptoms. Open-label Extension Baseline (OLEB) is defined as the most recent measurement prior to the first administration of study drug in KAR-008. The assessments performed on Visit 10 (Day 35) of studies KAR-007 or KAR-009 will be considered for OLEB baseline along with any additional procedures that will be performed on Day 0 of KAR-008.
  4. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Score at Week 52 [Open-labe extension baseline, week 52]
    PANSS positive score is the sum of all PANSS 7 positive symptom scales with a minimum score of 7 and a maximum score of 49. Higher scores indicate more severe symptoms. Participants are rated from 1 to 7 on each symptom scale. The positive symptoms in schizophrenia are the excess or distortion of normal function such as hallucinations, delusions, grandiosity, and hostility. Open-label Extension Baseline (OLEB) is defined as the most recent measurement prior to the first administration of study drug in KAR-008. The assessments performed on Visit 10 (Day 35) of studies KAR-007 or KAR-009 will be considered for OLEB baseline along with any additional procedures that will be performed on Day 0 of KAR-008.
  5. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Score at Week 52 [Open-label extension baseline, week 52]
    PANSS negative score is the sum of all PANSS 7 negative symptom scales with a minimum score of 7 and a maximum score of 49. Higher scores indicate more severe symptoms. Participants are rated from 1 to 7 on each symptom scale. The negative symptoms in schizophrenia are the diminution or loss of normal functions. Open-label Extension Baseline (OLEB) is defined as the most recent measurement prior to the first administration of study drug in KAR-008. The assessments performed on Visit 10 (Day 35) of studies KAR-007 or KAR-009 will be considered for OLEB baseline along with any additional procedures that will be performed on Day 0 of KAR-008.
  6. Change From Baseline in PANSS Negative Marder Factor Score at Week 52 [Open-label extension baseline, week 52]
    PANSS Negative Marder Factor Score is the sum of 5 negative scales and 2 general scales (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). Participants are rated from 1 to 7 on each symptom scale. Higher score indicates more severe symptoms. The negative symptoms in schizophrenia are the diminution or loss of normal functions. Open-label Extension Baseline (OLEB) is defined as the most recent measurement prior to the first administration of study drug in KAR-008. The assessments performed on Visit 10 (Day 35) of studies KAR-007 or KAR-009 will be considered for OLEB baseline along with any additional procedures that will be performed on Day 0 of KAR-008.
  7. Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 52 [Open-label extension baseline, week 52]
    Completed independently by a clinician, the CGI-S categorizes the severity of the illness as: 1 = Normal, not at all ill; 2 = Borderline mentally ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; and 7 = Among the most extremely ill patients, by asking the clinical 1 question and providing a rating based upon observed and reported symptoms, behavior, and function in the past 7 days to reflect the average severity level across the 7 days. Higher score indicates more severe illness. Open-label Extension Baseline (OLEB) is defined as the most recent measurement prior to the first administration of study drug in KAR-008. The assessments performed on Visit 10 (Day 35) of studies KAR-007 or KAR-009 will be considered for OLEB baseline along with any additional procedures that will be performed on Day 0 of KAR-008.
  8. Percentage of PANSS Responders With >=30% Reduction in PANSS Total Score at Week 52 [At week 52]
    A PANSS responder is defined as a participant with reduction from open-label extension baseline (OLEB) of at least a 30% improvement at Week 52 in the PANSS total score. 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. PANSS total score is the sum of all 30 items with a minimum score of 30 and a maximum score of 210. Higher scores indicate more severe symptoms. OLEB is defined as the most recent measurement prior to the first administration of study drug in KAR-008. The assessments performed on Visit 10 (Day 35) of studies KAR-007 or KAR-009 will be considered for OLEB baseline along with any additional procedures that will be performed on Day 0 of KAR-008.

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

    Study Documents (Full Text)

    More Information

    Additional Relevant MeSH Terms

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