A Phase 3, Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adults With DSM-5 Schizophrenia
Overview
- Phase
- Phase 3
- Intervention
- Xanomeline and Trospium Chloride Capsules
- Conditions
- Schizophrenia
- Sponsor
- Karuna Therapeutics
- Enrollment
- 252
- Locations
- 20
- Primary Endpoint
- Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 5
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a Phase 3, randomized, double-blind, parallel-group, placebo-controlled, multicenter inpatient study to examine the efficacy and safety of KarXT in adult subjects who are acutely psychotic with a Diagnostic and Statistical Manual Fifth Edition (DSM-5) diagnosis of schizophrenia. The primary objective of the study is to assess the efficacy of KarXT (a fixed combination of xanomeline 125 mg and trospium chloride 30 mg twice daily [BID]) versus placebo in reducing Positive and Negative Syndrome Scale (PANSS) total scores in adult inpatients with a DSM-5 diagnosis of schizophrenia. The secondary objectives of the study are to evaluate improvement in disease severity and symptoms, safety and tolerability, and pharmacokinetics in adult inpatients with a DSM-5 diagnosis of schizophrenia.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject is aged 18 to 65 years, inclusive, at screening.
- •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 (oral and written) in English to consent
- •Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 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 psychotic symptoms, with onset less than 2 months before screening.
- •The subject requires hospitalization for this acute exacerbation or relapse of psychotic symptoms.
- •If already an inpatient at screening, has been hospitalized for less than 2 weeks for the current exacerbation at the time of screening.
- •Positive and Negative Syndrome Scale total score between 80 and 120, inclusive. Score of ≥4 (moderate or greater) for ≥2 of the following Positive Scale (P) items:
- •Item 1 (P1; delusions)
Exclusion Criteria
- •Any primary DSM-5 disorder other than schizophrenia within 12 months before screening (confirmed using MINI version 7.0.2 at screening). Symptoms of mild mood dysphoria or anxiety are allowed as long as these symptoms are not the primary focus of treatment. 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 they can be allowed into the study.
- •Subjects who are newly diagnosed or are experiencing their first treated episode of schizophrenia.
- •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.
- •Subjects with HIV, cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections based on either medical history or liver function test results.
- •History 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.
- •Risk for suicidal behavior during the study as determined by the investigator's clinical assessment and Columbia-Suicide Severity Rating Scale (C-SSRS).
- •Clinically significant abnormal finding on the physical examination, medical history, ECG, or clinical laboratory results at screening.
- •Subjects cannot currently (within 5 half-lives or 1 week, whichever is longer, before baseline \[Day -1\]) be receiving oral antipsychotic medications; monoamine oxidase inhibitors; anticonvulsants (eg, lamotrigine, Depakote); tricyclic antidepressants (eg, imipramine, desipramine); selective serotonin reuptake inhibitors; or any other psychoactive medications except for as needed anxiolytics (eg, lorazepam, chloral hydrate).
- •Pregnant, lactating, or less than 3 months postpartum.
Arms & Interventions
KarXT
Intervention: Xanomeline and Trospium Chloride Capsules
Placebo
Intervention: Placebo
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 are rated from 1 to 7 on each symptom scale. It takes approximately 45 to 50 minutes to administer. 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
- 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) Negative Score at Week 5(Baseline and Week 5)
- Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Factor Negative Score(Baseline and Week 5)
- Change From Baseline Clinical Global Impression - Severity (CGI-S) Score at Week 5(Baseline and Week 5)
- Percentage of Positive and Negative Syndrome Scale (PANSS) Responders (>=30% Change in PANSS Total Score) at Week 5(Baseline and Week 5)