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

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

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.

Study Overview

• Status: Terminated
• Conditions: Panic Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Darigabat

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Phoenix, Arizona
  • California
    • Lafayette, California, United States, 94549
      • Lafayette, California
    • Los Angeles, California, United States, 90025
      • Los Angeles, California
    • Oceanside, California, United States, 92056
      • Oceanside, California
    • Orange, California, United States, 92868
      • Orange, California
    • Riverside, California, United States, 92506
      • Riverside, California
    • San Jose, California, United States, 95124
      • San Jose, California
    • Torrance, California, United States, 90502
      • Torrance, California
  • Florida
    • Miami, Florida, United States, 33175
      • Miami, Florida
    • North Miami Beach, Florida, United States, 33162
      • North Miami Beach, Florida
    • Orlando, Florida, United States, 32807
      • Orlando, Florida
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta, Georgia
    • Decatur, Georgia, United States, 30030
      • Decatur, Georgia
    • Savannah, Georgia, United States, 31405
      • Savannah, Georgia
  • Illinois
    • Elgin, Illinois, United States, 60123
      • Elgin, Illinois
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Overland Park, Kansas
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston, Massachusetts
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Las Vegas, Nevada
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Berlin, New Jersey
  • New York
    • Brooklyn, New York, United States, 11229
      • Brooklyn, New York
    • Brooklyn, New York, United States, 11235
      • Brooklyn, New York
    • New York, New York, United States, 10016
      • New York, New York
    • Rochester, New York, United States, 14618
      • Rochester, New York
    • Staten Island, New York, United States, 10314
      • Staten Island, New York
  • North Carolina
    • Monroe, North Carolina, United States, 28112
      • Monroe, North Carolina
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Oklahoma City, Oklahoma
  • Pennsylvania
    • West Chester, Pennsylvania, United States, 19380
      • West Chester, Pennsylvania
  • Texas
    • Austin, Texas, United States, 78737
      • Austin, Texas
    • DeSoto, Texas, United States, 75115
      • DeSoto, Texas
  • Utah
    • Draper, Utah, United States, 84020
      • Draper, Utah
  • Washington
    • Everett, Washington, United States, 98201
      • Everett, Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Standard Mini International Neuropsychiatric Interview (MINI)
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Darigabat; Participants will receive darigabat, up to a maximum dose of 12.5 mg, orally, BID, for 2 weeks during the Titration Period and thereafter, 25 mg, orally, BID for 12 weeks during the Maintenance Treatment Period.	Drug: Darigabat; Oral tablets; Other Names: CVL-865
Placebo Comparator: Placebo; 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; Oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Free of Panic Attacks as Assessed by Participant Daily eDiary During the Last Two Weeks of the Maintenance Treatment Period	Numerator is the number of participants in the period who were panic free and had no fewer that 12 eDiary entries. Denominator is the number of participants in the period who were panic free and had no fewer than 12 eDiary entries in the corresponding time period plus anyone who had an eDiary entry and reported a panic attack in the corresponding time period, regardless of number of eDiary entries.	Week 13-14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Panic Disorder Severity Scale (PDSS) Total Score at Week 14	The Panic Disorder Severity Scale (PDSS) is a 7-item scale, with each item rated on a 5-point scale (0-4), allowing a total of 0-28 where higher score reflects greater disease severity.	Week 14 (Day 98)
Change From Baseline in Panic Attack Frequency During the Last Two Weeks of the Maintenance Treatment Period	Panic attack frequency is defined as the total number of panic attacks over each two-week interval divided by the total number of days the eDiary was completed in the same analysis period multiplied by 14. Participants with a minimum of 7 completed diary days in a two-week interval will be considered for panic attack frequency, otherwise will be considered missing.	Week 13-14
Change From Baseline in the Proportion of Participants Free of Panic Attacks as Assessed by Participant Daily Diary by Two-Week Intervals	Numerator is the number of participants who were panic free and had no fewer than 12 eDiary entries in the corresponding time period. Denominator is the number of participants in the period who were panic free and had no fewer than 12 eDiary entries in the corresponding time period plus anyone who had an eDiary entry and reported a panic attack in the corresponding time period, regardless of number of eDiary entries. * Last Two Weeks of Maintenance Treatment Prior to Subject's Completion/Early Termination = Includes assessments made in the last two weeks of the Maintenance Period prior to completion/early termination for all subjects that had at least 2 weeks of data in the maintenance period, which would be Maintenance Week 11-12 for subjects who completed and earlier for subjects who terminated study participation prior to completion.	Baseline through Week 14 (2 Weeks Titration and 12 Weeks Maintenance Treatment)
Change From Baseline at All Time Points up to Week 14 in the PDSS Total Score	The Panic Disorder Severity Scale (PDSS) is a 7-item scale, with each item rated on a 5-point scale (0-4), allowing a total of 0-28 where higher score reflects greater disease severity. Change from baseline = value - baseline value; n = number of participants with a non-missing value; overall N = number of participants in treatment group	Baseline through Week 14
Change From Baseline in Panic Attack Frequency by Two-Week Intervals Through Week 14	Panic attack frequency is defined as the total number of panic attacks over each two-week interval divided by the total number of days the eDiary was completed in the same analysis period multiplied by 14. Participants with a minimum of 7 completed diary days in a two-week interval will be considered for panic attack frequency, otherwise will be considered missing. Change from baseline = value - baseline value; n = number of participants with a non-missing value; overall N = number of participants in treatment group * Last Two Weeks of Maintenance Treatment Prior to Subject's Completion/Early Termination = Includes assessments made in the last two weeks of the Maintenance Period prior to completion/early termination for all subjects that had at least 2 weeks of data in the maintenance period, which would be Maintenance Week 11-12 for subjects who completed and earlier for subjects who terminated study participation prior to completion.	Baseline through Week 14 (2 Weeks Titration and 12 Weeks Maintenance Treatment)
Change From Baseline at All Time Points up to Week 14 in the Clinical Global Impression-Severity of Symptoms Scale (CGI-S) Score	The Clinical Global Impression-Severity (CGI-S) scale is a single item 7-point scale, with panic order severity rated from 1 (normal) through to 7 (most severely ill). Change from baseline = value - baseline value; n = number of participants with a non-missing value; overall N = number of participants in treatment group.	Baseline through Week 14
Change From Baseline at All Time Points up to Week 14 in the Hamilton Anxiety Scale (HAM-A) Total Score	The Hamilton Anxiety Scale (HAM-A) is a 14-item scale measures severity of anxiety symptoms. Each item is scored on a scale from 0 (not present) to 4 (severe) resulting in a total score range of 0 to 56, with higher scores indicating more severe anxiety. Change from baseline = value - baseline value; n = number of participants with a non-missing value; overall N = number of participants in treatment group.	Baseline through Week 14
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	A Treatment-Emergent Adverse Event (TEAE) is any event reported on the CRF that occurs on or after the initiation of IMP and through follow-up contact.	From Day 1 through Week 18
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Results	12-lead ECGs recordings were obtained after the participant had been supine and at rest for at least 3 minutes. The number of participants with significant abnormalities is reported by 'change from baseline in QT interval as corrected for heart rate by Fridericia's formula (QTcF)'.	Up to Week 14
Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessment Values	Protocol-required safety laboratory tests were performed, including hematology, chemistry and urinalysis tests. Reported here is the number of participants with clinically significant changes in these laboratory tests.	Up to Week 18
Number of Participants With Clinically Significant Changes in Vital Sign Measurements	Vital signs were measured with the participant in a sitting/semi-recumbent position after 3 minutes rest and included temperature, systolic and diastolic blood pressure, respiratory rate, and heart rate. Reported here is the 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	A complete physical examination consisted of measurement of weight and a review of the following body systems: head, ears, eyes, nose, mouth, skin, heart, lungs, lymph nodes, and gastrointestinal, genitourinary, and musculoskeletal systems. A full neurological examination included an assessment of the participant's mental status (level of consciousness, orientation, speech, memory, etc), cranial nerves, motor (muscle appearance, tone, strength, and reflexes), sensation (including Romberg sign), coordination, and gait. Reported here is the number of participants with clinically significant changes in physical or neurological examination results.	Up to Week 14
Number of Participants With Changes in Suicidality Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)	The C-SSRS rates an individual's degree of suicidal ideation (SI) on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent." The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent). Reported here is the number of participants with changes in suicidality assessed using the C-SSRS scale.	Up to Week 14
Number of Participants With Withdrawal Symptoms Assessed Using the Penn Physician's Withdrawal Checklist (PWC)	The PWC is a 20-item scale to measure discontinuation symptoms after stopping a medication for anxiety disorders. All 20 items are rated on a 4-point numeric-rating scale ranging from 0 (not present), 1 (mild), 2 (moderate), to 3 (severe). A total score, ranging 0 to 60, was calculated in addition to the individual scores for each item. Lower scores indicate less severity in discontinuation symptoms. Reported here is the number of participants with withdrawal symptoms assessed using the PWC.	Up to Week 15

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2023
• Primary Completion (Actual): March 31, 2025
• Study Completion (Actual): March 31, 2025

Study Registration Dates

• First Submitted: June 15, 2023
• First Submitted That Met QC Criteria: July 10, 2023
• First Posted (Actual): July 12, 2023

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Panic Disorder
• Other Study ID Numbers: CVL-865-PA-2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No