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

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.

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.

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.

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

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.

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.

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.

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.

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)'.

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.

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.

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.

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.

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.