Panic Disorder
Conditions
Brief summary
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.
Interventions
DRUGDarigabat
Oral tablets
DRUGPlacebo
Oral tablets
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Free of Panic Attacks as Assessed by Participant Daily eDiary During the Last Two Weeks of the Maintenance Treatment Period | Week 13-14 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Panic Disorder Severity Scale (PDSS) Total Score at Week 14 | Week 14 (Day 98) | 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 in Panic Attack Frequency During the Last Two Weeks of the Maintenance Treatment Period | Week 13-14 | 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 in the Proportion of Participants Free of Panic Attacks as Assessed by Participant Daily Diary by Two-Week Intervals | Baseline through Week 14 (2 Weeks Titration and 12 Weeks Maintenance Treatment) | 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. |
| Change From Baseline at All Time Points up to Week 14 in the PDSS Total Score | Baseline through 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. Change from baseline = value - baseline value; n = number of participants with a non-missing value; overall N = number of participants in treatment group |
| Change From Baseline in Panic Attack Frequency by Two-Week Intervals Through Week 14 | Baseline through Week 14 (2 Weeks Titration and 12 Weeks Maintenance Treatment) | 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. |
| 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 | 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. |
| Change From Baseline at All Time Points up to Week 14 in the Hamilton Anxiety Scale (HAM-A) Total Score | Baseline through Week 14 | 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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From Day 1 through Week 18 | 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. |
| Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Results | Up to Week 14 | 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)'. |
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessment Values | Up to Week 18 | 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. |
| Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Up to Week 14 | 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. |
| Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results | Up to Week 14 | 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. |
| Number of Participants With Changes in Suicidality Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Up to Week 14 | 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. |
| Number of Participants With Withdrawal Symptoms Assessed Using the Penn Physician's Withdrawal Checklist (PWC) | Up to Week 15 | 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. |
Countries
United States
Contacts
STUDY_DIRECTORABBVIE INC.
AbbVie
Participant flow
Recruitment details
The Sponsor terminated the study due to significant enrollment and study design challenges.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 43.5 years STANDARD_DEVIATION 13.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 67 Participants |
| Sex: Female, Male Female | 61 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 40 |
| other Total, other adverse events | 20 / 40 | 21 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 |
Outcome results
None listed