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

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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

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.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: Xanomeline and Trospium Chloride Capsules Drug: Placebo Capsules Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 182 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-blinded Study to Assess the Safety, Tolerability, and Efficacy of KarXT in Hospitalized Adults With DSM-5 Schizophrenia
Actual Study Start Date : September 18, 2018
Estimated Primary Completion Date : November 5, 2019
Estimated Study Completion Date : November 5, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arm Intervention/treatment
Experimental: KarXT 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

Placebo Comparator: Placebo Drug: Placebo Capsules
Placebo Capsules




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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): NCT03697252


Locations
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United States, Arkansas
Woodland International Research Group, LLC
Little Rock, Arkansas, United States, 72211
United States, California
Synergy East
Lemon Grove, California, United States, 91945
Collaborative Neuroscience Network, LLC.
Long Beach, California, United States, 90806
NRC Research Institute
Orange, California, United States, 92868
Artemis Institute for Clinical Research
San Diego, California, United States, 92103
United States, Georgia
Atlanta Center for Medical Research
Atlanta, Georgia, United States, 30331
United States, Maryland
CBH Health, LLC
Gaithersburg, Maryland, United States, 20877
United States, New Jersey
Hassman Research Institute
Berlin, New Jersey, United States, 08009
United States, Ohio
Midwest Clinical Research Center (and IP Shipment)
Dayton, Ohio, United States, 45417
United States, Texas
Community Clinical Research, Inc.
Austin, Texas, United States, 78754
InSite Clinical Research, LLC
DeSoto, Texas, United States, 75115
Pillar Clinical Research, LLC
Richardson, Texas, United States, 75080
Sponsors and Collaborators
Karuna Pharmaceuticals
Investigators
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Study Director: Stephen Brannan, MD Karuna Pharmaceuticals

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Responsible Party: Karuna Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03697252     History of Changes
Other Study ID Numbers: KAR-004
First Posted: October 5, 2018    Key Record Dates
Last Update Posted: August 14, 2019
Last Verified: August 2019
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
Keywords provided by Karuna Pharmaceuticals:
Schizophrenia
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