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A Study to Assess Safety and Efficacy of KarXT in Adult Patients With Schizophrenia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03697252
Recruitment Status : Active, not recruiting
First Posted : October 5, 2018
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
Karuna Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE October 3, 2018
First Posted Date  ICMJE October 5, 2018
Last Update Posted Date August 14, 2019
Actual Study Start Date  ICMJE September 18, 2018
Estimated Primary Completion Date November 5, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 19, 2018)
Change in Positive and Negative Syndrome Scale (PANSS) total score at Week 5 [ Time Frame: 5 Weeks ]
The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Subjects 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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 3, 2018)
Change in Positive and Negative Syndrome Scale (PANSS) total score at Week 5 [ Time Frame: 5 Weeks ]
Change History Complete list of historical versions of study NCT03697252 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2018)
  • Change in PANSS positive score [ Time Frame: 5 Weeks ]
    The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Subjects 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.
  • Change in PANSS Marder Factor score [ Time Frame: 5 Weeks ]
    The PANSS Marder Factor score includes positive symptoms (8 scales), negative symptoms (7 scales), disorganized thinking/behavior (7 scales), depression/anxiety (4 scales), and hostility/excitement (4 scales) factors from the PANSS. Subjects 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.
  • Change in Clinical Global Impression‒Severity (CGI-S) score [ Time Frame: 5 Weeks ]
    The CGI-S modified asks the clinician 1 question: "Considering your total clinical experience, how mentally ill is the subject at this time?" The clinician's answer is 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 subjects.
  • Percent of CGI-S responders (with CGI-S scale equal to 1 or 2) [ Time Frame: 5 Weeks ]
    The CGI-S modified asks the clinician 1 question: "Considering your total clinical experience, how mentally ill is the subject at this time?" The clinician's answer is 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 subjects.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 3, 2018)
  • Change in PANSS positive score [ Time Frame: 5 Weeks ]
  • Change in PANSS Marder Factor score [ Time Frame: 5 Weeks ]
  • Change in Clinical Global Impression‒Severity (CGI-S) score [ Time Frame: 5 Weeks ]
  • Percent of CGI-S responders (with CGI-S scale equal to 1 or 2) [ Time Frame: 5 Weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess Safety and Efficacy of KarXT in Adult Patients With Schizophrenia
Official Title  ICMJE A Phase 2, Randomized, Double-blinded Study to Assess the Safety, Tolerability, and Efficacy of KarXT in Hospitalized Adults With DSM-5 Schizophrenia
Brief Summary This is a Phase 2, randomized, double-blinded, placebo-controlled, inpatient study to examine the efficacy, safety, and tolerability profile of KarXT in adult subjects diagnosed with DSM-5 schizophrenia who are in an acute exacerbation phase. The primary objective of the study is to assess the efficacy of KarXT (a fixed combination of xanomeline and trospium chloride) (xanomeline 125 mg/trospium 30 mg twice daily [BID]) versus placebo in reducing Positive and Negative Syndrome Scale (PANSS) total scores in adult inpatients with a Diagnostic and Statistical Manual‒Fifth Edition (DSM-5) diagnosis of schizophrenia. The secondary objectives of the study are to assess overall safety and tolerability of KarXT in adult inpatients with a DSM-5 diagnosis of schizophrenia.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Schizophrenia
Intervention  ICMJE
  • Drug: Xanomeline and Trospium Chloride Capsules
    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 8-34 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. Dosing must not change after Visit 7 of the study (at 21 ± 2 days of dosing) and may be decreased for tolerability reasons no more than once during the study.
    Other Name: KarXT
  • Drug: Placebo Capsules
    Placebo Capsules
Study Arms  ICMJE
  • Experimental: KarXT
    Intervention: Drug: Xanomeline and Trospium Chloride Capsules
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo Capsules
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 13, 2019)
182
Original Estimated Enrollment  ICMJE
 (submitted: October 3, 2018)
160
Estimated Study Completion Date  ICMJE November 5, 2019
Estimated Primary Completion Date November 5, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subject is aged 18-60 years, inclusive, at screening
  2. Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 (American Psychiatric Association 2013) criteria and confirmed by Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorder Studies (MINI) version 7.0.2.
  3. Subject is experiencing an acute exacerbation or relapse of symptoms, with onset less than 2 months before screening
  4. Positive and Negative Syndrome Scale total score between 80 and 120, inclusive, at screening

    1. Score of ≥ 4 (moderate or greater) for ≥ 2 of the following Positive Scale (P) items at screening:
    2. Item 1 (P1; delusions)
    3. Item 2 (P2; conceptual disorganization)
    4. Item 3 (P3; hallucinatory behavior)
    5. Item 6 (P6; suspiciousness/persecution)
  5. There should not be a change (improvement) in PANSS total score between screening and baseline of more than 20%
  6. Subjects taking a depot antipsychotic could not have received a dose of medication for at least 1 and a half injection cycles before baseline (eg, 3 or more weeks off for a 2-week cycle)
  7. Subject is capable of providing informed consent

    1. A signed ICF must be provided before any study assessments are performed
    2. Subject must be fluent (oral and written) in English in order to consent
  8. Subject must have CGI-S score of ≥ 4 at screening and baseline visits
  9. Body mass index must be ≥ 18 and ≤ 40 kg/m2
  10. Both females of child bearing potential and males with partners of child bearing potential must be willing to use a double-barrier method of birth control (ie, any double combination of male or female condom with spermicidal gel, diaphragm, sponge, or cervical cap with spermicidal gel) during the study and for 7 days after the last dose of study drug.
  11. Subject has an identified reliable informant

Exclusion Criteria:

  1. Any primary DSM-5 disorder other than schizophrenia within 12 months before screening (confirmed using MINI version 7.0.2 at screening)
  2. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results, to exclude patients with human immunodeficiency virus (HIV), cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections based on the liver function test results.
  3. History of or high risk of urinary retention, gastric retention, or narrow-angle glaucoma
  4. History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months
  5. Has a DSM-5 diagnosis of moderate to severe substance abuse disorder (except tobacco use disorder) within the 12 months before screening (confirmed using MINI version 7.0.2 at screening), or current abuse as determined by urine toxicology screen or alcohol test. A screening subject with mild substance abuse disorder within the 12 months before screening must be discussed and agreed upon with the medical monitor before he/she can be allowed into the study.
  6. Clinically significant abnormal finding on the physical examination, medical history, ECG, or clinical laboratory results at screening
  7. Pregnant, lactating, or less than 3 months postpartum. Sperm donation is not allowed for 90 days after the final dose of study drug
  8. 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 their ability to adhere to the protocol visit schedule or fulfill visit requirements
  9. Subject has had psychiatric hospitalization(s) for more than 30 days (cumulative) during the 90 days before screening
  10. Subject has a history of treatment resistance to schizophrenia medications defined as failure to respond to 2 adequate courses of pharmacotherapy (a minimum of 4 weeks at an adequate dose per the label) or required clozapine within the last 12 months
  11. Risk of violent or destructive behavior
  12. Current involuntary hospitalization or incarceration
  13. Participation in another clinical study in which the subject received an experimental or investigational drug agent within 3 months of screening
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03697252
Other Study ID Numbers  ICMJE KAR-004
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  ICMJE
Plan to Share IPD: No
Responsible Party Karuna Pharmaceuticals
Study Sponsor  ICMJE Karuna Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Stephen Brannan, MD Karuna Pharmaceuticals
PRS Account Karuna Pharmaceuticals
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP