A Phase 2, Randomized, Double-blinded Study to Assess the Safety, Tolerability, and Efficacy of KarXT in Hospitalized Adults With DSM-5 Schizophrenia
Overview
- Phase
- Phase 2
- Intervention
- Xanomeline and Trospium Chloride Capsules
- Conditions
- Schizophrenia
- Sponsor
- Karuna Therapeutics
- Enrollment
- 182
- Locations
- 12
- Primary Endpoint
- Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 5
- Status
- Completed
- Last Updated
- 5 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject is aged 18-60 years, inclusive, at screening
- •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.
- •Subject is experiencing an acute exacerbation or relapse of symptoms, with onset less than 2 months before screening
- •Positive and Negative Syndrome Scale total score between 80 and 120, inclusive, at screening
- •Score of ≥ 4 (moderate or greater) for ≥ 2 of the following Positive Scale (P) items at screening:
- •Item 1 (P1; delusions)
- •Item 2 (P2; conceptual disorganization)
- •Item 3 (P3; hallucinatory behavior)
- •Item 6 (P6; suspiciousness/persecution)
- •There should not be a change (improvement) in PANSS total score between screening and baseline of more than 20%
Exclusion Criteria
- •Any primary DSM-5 disorder other than schizophrenia within 12 months before screening (confirmed using MINI version 7.0.2 at screening)
- •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.
- •History of or high risk of urinary retention, gastric retention, or narrow-angle glaucoma
- •History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months
- •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.
- •Clinically significant abnormal finding on the physical examination, medical history, ECG, or clinical laboratory results at screening
- •Pregnant, lactating, or less than 3 months postpartum. Sperm donation is not allowed for 90 days after the final dose of study drug
- •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
- •Subject has had psychiatric hospitalization(s) for more than 30 days (cumulative) during the 90 days before screening
- •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
Arms & Interventions
KarXT
Intervention: Xanomeline and Trospium Chloride Capsules
Placebo
Intervention: Placebo Capsules
Outcomes
Primary Outcomes
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 5
Time Frame: Baseline and Week 5
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 were 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.
Secondary Outcomes
- Number of Participants With Each Clinical Global Impression - Severity (CGI-S) Score at Baseline and 5 Weeks(Baseline and Week 5)
- Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Score at Week 5(Baseline and Week 5)
- Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Score at Week 5(Baseline and Week 5)
- Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Factor Score(Baseline and Week 5)
- Percentage of Participants Who Were Clinical Global Impression - Severity of Illness (CGI-S) Responders(Week 5)