An Open-Label Tolerability and Efficacy Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With 22q11.2 Deletion Syndrome

Time frame

Period 1: Baseline (Day 1) and Week 14 (Day 98 ± 3 days); Period 2: Week 14 (Day 98 ± 3 days) and Week 38 (Day 266 ± 3 days).Period 2: Baseline (Day 1 of

Measure

MEAN · score on a scale

Reporting status

POSTED

The Anxiety, Depression and Mood Scale (ADAMS) was completed by the parent/caregiver with support from the site staff. The ADAMS is comprised of 28 items (question 3 is counted in two subscales), which are rated on a scale of "0=not a problem" to "3=severe problem". The ADAMS consists of 5 subscales: depressed mood subscale (scale range from 0 to 21), general anxiety subscale (scale range from 0 to 21), manic/hyperactive behavior subscale (scale range from 0 to 15), obsessive/compulsive behavior subscale (scale range from 0 to 9) and social avoidance subscale (scale range from 0 to 21). Total score range is 0 to 84. Higher scores indicate higher severity/worse outcome. Baseline was defined as the last assessment prior to the first dose of ZYN002.

Population: The mITT analysis set included safety participants who had at least 1 post baseline efficacy assessment. Data were collected for all participants regardless of ZYN002 dose because PK modeling suggested similar exposures for the weight-based dosing regimens.

Time frame

Period 1: Baseline (Day 1) and Week 14 (Day 98 ± 3 days); Period 2: Week 14 (Day 98 ± 3 days) and Week 38 (Day 266 ± 3 days).

Measure

MEAN · score on a scale

Reporting status

POSTED

The Clinical Global Impression-Severity (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment relative to the clinician's past experience with participants who have the same diagnosis. Considering total clinical experience, a participant was assessed on severity of mental illness at the time of rating as follows: 1= normal, not at all ill; 2= borderline mentally ill; 3= mildly ill; 4= moderately ill; 5= markedly ill; 6= severely ill; or 7= extremely ill. The CGI-S score range from 0 (not a problem) to 7 (severe problem). Higher scores indicate higher severity. Baseline was defined as the last assessment prior to the first dose of ZYN002.

Population: The mITT analysis set included safety participants who had at least 1 post baseline efficacy assessment. Data were collected for all participants regardless of ZYN002 dose because PK modeling suggested similar exposures for the weight-based dosing regimens.

Time frame

Period 1: Week 14 (Day 98 ± 3 days); Period 2: Week 38 (Day 266 ± 3 days).

Measure

COUNT_OF_PARTICIPANTS · Participants

Reporting status

POSTED

The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1= very much improved; 2= much improved; 3= minimally improved; 4= no change; 5= minimally worse; 6= much worse; or 7= very much worse. Baseline was defined as the last assessment prior to the first dose of ZYN002. Higher scores indicate worse outcome.

Population: The mITT analysis set included safety participants who had at least 1 post baseline efficacy assessment. Data were collected for all participants regardless of ZYN002 dose because PK modeling suggested similar exposures for the weight-based dosing regimens.

Time frame

Period 1: Week 14 (Day 98 ± 3 days); Period 2: Week 38 (Day 266 ± 3 days).

Measure

COUNT_OF_PARTICIPANTS · Participants

Reporting status

POSTED

The parent/caregiver was asked the following question "What are the three behavioral, emotional, or social problems that most impacted your son/daughter and his/her family in approximately the past year?". At each study visit the parent/caregiver was reminded of their responses from the screening visit in order to rate the 3 questions for improvement or worsening.

Population: The mITT analysis set included safety participants who had at least 1 post baseline efficacy assessment.

Time frame

Period 1: Baseline (Day 1) and Week 14 (Day 98 ± 3 days); Period 2: Week 14 (Day 98 ± 3 days) and Week 38 (Day 266 ± 3 days).

Measure

MEAN · score on a scale

Reporting status

POSTED

The Pediatric Anxiety Rating Scale-Revised (PARS-R) is a clinician-rated caregiver interview that covers 61 behaviors related to anxiety. The interviewer assesses 7 items: overall severity of anxiety feelings; overall number, frequency, and severity of anxiety symptoms; overall severity of anxiety (physical symptoms); overall avoidance of anxiety-provoking situations; and anxiety interference with family and peer relationships and/or performance at home or outside of the home. Each of the 7 severity items was scored on a scale of 1 to 5, with 5 being the most severe and frequent. The total score for the PARS-R is the sum of the 7 items; range from 0 (not a problem) to 35 (severe problem). Higher scores indicate higher severity. Baseline was defined as the last assessment prior to the first dose.

Population: The mITT analysis set included safety participants who had at least 1 post baseline efficacy assessment. Data were collected for all participants regardless of ZYN002 dose because PK modeling suggested similar exposures for the weight-based dosing regimens.

Time frame

Week 14 (Day 98 ± 3 days) and Week 38 (Day 266 ± 3 days).

Measure

MEAN · nanogram per milliliter

Reporting status

POSTED

Blood samples were collected to determine the plasma concentrations of cannabidiol and Δ9-tetrahydrocannabinol.

Population: The Pharmacokinetic population included all participants who received at least 1 application of study drug and had a plasma concentration obtained from at least 1 post baseline assessment.

Data were collected as a single arm because, based on pharmacokinetics (PK) modeling, exposure is consistent between doses. The study protocol and statistical analysis plan (SAP) were not amended. Instead, the Sponsor has written a Note to File to state how data were collected.