A Study to Evaluate Efficacy, Safety, and Tolerability of Darigabat in Participants With Panic Disorder

Study Overview
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Brief Summary
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The purpose of this trial is to measure the efficacy, safety, and tolerability of darigabat (25 milligrams [mg] twice daily [BID]) compared with placebo in participants with panic disorder.

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of Darigabat in Participants With Panic Disorder

Conditions
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Panic Disorder

Intervention / Treatment
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* Drug: Darigabat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary diagnosis of panic disorder based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Text Revision (DSM-5-TR), as confirmed by the Mini International Neuropsychiatric Interview (MINI) for Psychotic Disorders Participant has had a minimum of 8 panic attacks, with no week free of panic attacks, in the month prior to the Screening Visit. In the 2 weeks prior to the Baseline Visit, the participant must have had at least 4 panic attacks and no week free of panic attacks Participants with a PDSS total score ≥12 at the Screening and Baseline Visits Body mass index of 17.5 to 40.0 kilograms per meter square (kg/m2) and a total body weight >48 kg at Screening Exclusion Criteria: Participants who have a current significant psychiatric comorbidity Any newly initiated evidence-based psychotherapy, including cognitive behavioral therapy (CBT) Any exposure-based therapy is prohibited throughout the duration of the trial Participants with a current history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, hematological, immunological, or neurological disease Participants who answer Yes on the following C-SSRS Suicidal Ideation Items (within the last 6 months) Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) OR Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent) OR Participants who answer Yes on any of the 5 C-SSRS Suicidal Behavior Items (within the last 2 years) Any of the Suicidal Behavior items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) OR Participants who, in the opinion of the investigator, present a serious risk of suicide NOTE: Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Darigabat<br>Participants will receive darigabat, up to a maximum dose of 12.5 mg, orally, BID, for two weeks in the Titration Period and thereafter, 25 mg, orally, BID for 12 weeks in the Maintenance Treatment Period. | Drug: Darigabat<br>* Oral tablets<br>* Other names: CVL-865;|
| Placebo Comparator: Placebo<br>Participants will receive darigabat matching placebo, orally, BID for 2 weeks during the Titration period and thereafter for 12 weeks during the Maintenance Treatment Period. | Drug: Placebo<br>* Oral tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Free of Panic Attacks as Assessed by Participant Daily Diary During Maintenance Treatment Period |  | Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the Panic Disorder Severity Scale (PDSS) Total Score at Week 14 |  | Baseline and Week 14 | 
| Change from Baseline in Panic Attack Frequency During the Last Two Weeks of the Maintenance Treatment Period |  | Baseline, Week 13, and Week 14 | 
| Change from Baseline at all Time Points up to Week 15 in the Proportion of Participants Free of Panic Attacks as Assessed by Participant Daily Diary |  | Baseline through Week 15 | 
| Change from Baseline at all Time Points up to Week 14 in the PDSS Total Score and Subscores |  | Baseline through Week 14 | 
| Change from Baseline at all Time Points up to Week 15 in Panic Attack Frequency |  | Baseline through Week 15 | 
| Change from Baseline at all Time Points up to Week 14 in the Clinical Global Impression-Severity of Symptoms Scale (CGI-S) Score |  | Baseline through Week 14 | 
| Change from Baseline at all Time Points up to Week 14 in the Hamilton Anxiety Scale (HAM-A) Total Score |  | Baseline through Week 14 | 
| Number of Participants with Treatment-emergent Adverse Events (TEAEs) |  | From Day 1 through Week 18 | 
| Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Results |  | Up to Week 14 | 
| Number of Participants with Clinically Significant Changes in Clinical Laboratory Assessment Values |  | Up to Week 18 | 
| Number of Participants with Clinically Significant Changes in Vital Sign Measurements |  | Up to Week 14 | 
| Number of Participants with Clinically Significant Changes in Physical and Neurological Examination Results |  | Up to Week 14 | 
| Changes in Suicidality Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) |  | Up to Week 14 | 
| Number of Participants with Withdrawal Symptoms Assessed Using the Penn Physician's Withdrawal Checklist (PWC) |  | Up to Week 15 |