Clinical Study Of caNNabidiol in childrEn and adolesCenTs With Fragile X (CONNECT-FX)

Sponsor
Zynerba Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT03614663
Collaborator
(none)
212
21
2
24.1
10.1
0.4

Study Details

Study Description

Brief Summary

This trial will evaluate the efficacy and safety of ZYN002, a clear cannabidiol gel that can be applied to the skin (called transdermal application) twice a day for the treatment of behavioral symptoms of Fragile X Syndrome (FXS). Eligible participants will then participate in up to a 14 week treatment period, where all participants will receive placebo or active study drug. Patients ages 3 to < 18 years, will be eligible to participate.

Condition or Disease Intervention/Treatment Phase
  • Drug: ZYN002 - Cannabidiol Transdermal Gel
  • Other: Placebo Transdermal Gel
Phase 2/Phase 3

Detailed Description

This is a randomized, double-blind, placebo-controlled, multiple-center study, to assess the efficacy and safety of ZYN002, a pharmaceutically manufactured cannabidiol, formulated as a transdermal gel, for the treatment of children and adolescent with FXS. Approximately 204 male and female patients, ages 3 to < 18 years, will undergo a screening process. Eligible participants will be randomized 1:1 to either trial drug or placebo and will undergo a 14-week treatment period. Randomization will be stratified by gender, weight category and geographic region. All participants may receive placebo during the trial. Participants who are taking anti-seizure drugs may undergo an additional 1-2 weeks of blinded treatment to taper off study drug treatment. The assignment will be done by a computer generated system and neither the trial doctor or the participant or their caregivers will know which treatment is being given to them. The dose of the treatment will depend on the weight of the participants. If the participants weigh less than or equal to 35 kg, they will receive 2 sachets of the gel twice a day (1 sachet approximately every 12 hours) and if they weigh more than 35 kg, they will receive 4 sachets of gel per day (2 sachets approximately every 12 hours). Parents/ caregivers will be instructed on proper application of the gel. The gel will be applied to clean, dry, intact skin of the upper arms/ shoulders.

Blood samples will be collected for safety analysis of ZYN002. An independent analytical laboratory will also perform CGG repeat and methylation status analyses. Additionally, the parents/caregivers will be asked to complete some questionnaires. There will be other questionnaires and scales that will be completed at the site by the trial doctor.

After the final dose, patients will be followed weekly for 4 weeks by telephone, prior to discharge from the study.

Study Design

Study Type:
Interventional
Actual Enrollment :
212 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Placebo-Controlled Multiple-Center, Efficacy and Safety Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With Fragile X Syndrome
Actual Study Start Date :
Jun 12, 2018
Actual Primary Completion Date :
Jun 14, 2020
Actual Study Completion Date :
Jun 14, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: ZYN002 - Cannabidiol transdermal gel

ZYN002 supplied as a transdermal gel. Patients weighing less than or equal to 35 kg will be randomized to receive either 125 mg cannabidiol Q12H or placebo. Patients weighing greater than 35 kg will be randomized to receive 250 mg cannabidiol Q12H or placebo.

Drug: ZYN002 - Cannabidiol Transdermal Gel
Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery)

Placebo Comparator: Placebo transdermal gel

Matching ZYN002 placebo supplied as a transdermal gel.

Other: Placebo Transdermal Gel
Placebo formulated as a clear gel (transdermal delivery)
Other Names:
  • Placebo Comparator
  • Matching Placebo
  • Outcome Measures

    Primary Outcome Measures

    1. Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Social Avoidance Subscale - Full Analysis Set [Change from Baseline to end of treatment (Week 12)]

      The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is from 0 to 12, and a higher value indicates a worse outcome.

    2. Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Social Avoidance Subscale - Ad Hoc Analysis [Change from baseline to end of treatment (Week 12)]

      The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is from 0 and 12, and the higher score means a worse outcome.

    Secondary Outcome Measures

    1. Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Irritability Subscale - Full Analysis Set [Change from baseline to end of treatment (Week 12)]

      The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is between 0 and 54, and the higher score means a worse outcome.

    2. Aberrant Behavior Checklist-Community, Fragile X Factor Structure (ABC-C FXS) Socially Unresponsive/Lethargic Subscale - Full Analysis Set [Change from baseline to end of treatment (Week 12)]

      The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is from 0 and 39, and a higher mean indicates a worse outcome.

    3. Number of Participants With Any Improvement - Clinical Global Impressions- Improvement (CGI-I) - Full Analysis Set [Change in CGI-I at end of treatment (Week 12)]

      The Clinical Global Impressions- Improvement global improvement item is a 7-point Likert scale designed to measure behavioral symptomatic change at a specific time compared to baseline. CGI-I is a standard global measure of potential change with treatment in placebo-controlled pharmacotherapy trials in developmental disabilities. The score ranges form 1-very much improved to 7-very much worse. The percentage of patients with any improvement (minimally, much, very much improved) was assessed.

    4. Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Irritability Subscale - Ad Hoc Analysis [Change from baseline in ABC-C to end of treatment (Week 12)]

      The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is between 0 and 54, and the higher score means a worse outcome.

    5. Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Socially Unresponsive/Lethargic Subscale - Ad Hoc Analysis [Change from baseline in ABC-C to end of treatment (Week 12)]

      The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is from 0 to 39 , and the higher score means a worse outcome.

    6. Number of Participants With Any Improvement - Clinical Global Impressions- Improvement (CGI-I) - Ad Hoc Analysis [Change in CGI-I at end of treatment (Week 12)]

      The Clinical Global Impressions- Improvement global improvement item is a 7-point Likert scale designed to measure behavioral symptomatic change at a specific time compared to baseline. CGI-I is a standard global measure of potential change with treatment in placebo-controlled pharmacotherapy trials in developmental disabilities. The score ranges form 1-very much improved to 7-very much worse. The percentage of patients with any improvement (minimally, much, very much improved) was assessed.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    3 Years to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Male or female children and adolescents aged 3 to less than 18 years, at the time of Screening.

    • Diagnosis of FXS through molecular documentation of FMR1 full mutation.

    • Judged to be in good health based on physical exam, 12-lead ECG and clinical laboratory test results.

    • Patients must be assessed by the Investigator as being moderately to severely impacted due to FXS.

    • Patients taking psychotropic medication(s) should be on a stable regimen of not more than two such medications for at least fours weeks preceding Screening and must maintain that regimen throughout the study.

    • If patients are receiving non-pharmacological, behavioral and/or dietary interventions, they must be stable and have been doing so for three months prior to screening.

    • Patients and parents/caregivers must be adequately informed of the nature and risks of the study and given written informed consent prior to Screening.

    • In the Investigator's opinion, patients and parents/caregivers are reliable and willing and able to comply with all protocol requirements and procedures.

    Exclusion Criteria:
    • Females who are pregnant, nursing or planning a pregnancy.

    • Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin levels greater than or equal to 2 times the upper limit of normal or alkaline phosphatase levels greater than or equal to 3 times the upper limit of normal.

    • Use of a strong inhibitor/inducer of CYP3A4 or sensitive substrate of CYP3A4.

    • Use of minocycline for 30 days prior to screening or throughout the study.

    • Use of any benzodiazepine at screening or throughout the study.

    • Use of THC or CBD-containing product within three months of Screening Visit or during the study.

    • Change in pharmacologic or non-pharmacologic intervention during the course of the study.

    • Any skin disease or condition including eczema, psoriasis, melanoma, acne, contact dermatitis, scarring, imperfections, lesions, tattoos, or discoloration that may affect treatment application, application site assessments or absorption of the trial drug.

    • Patient is using the following ASMs: clobazam, phenobarbital, ethosuximide, felbamate or vigabatrin.

    • Patients has an advanced, severe or unstable disease that may interfere with the study outcome evaluations.

    • Patient has acute or progressive neurological disease, psychosis, schizophrenia or any other psychiatric disorder or severe mental abnormalities (other than FXS) that are likely to require changes in drug therapy or interfere with the study objectives or ability to adhere to protocol requirements.

    • Patient has suspected or confirmed cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, cardiac conduction problems, exercise-related cardiac events including syncope and pre-syncope, risk factors for Torsades de pointes (e.g. heart failure, hypokalemia, family history of Long QT Syndrome) or other serious cardiac problems.

    • History of treatment for, or evidence of drug abuse within the past year.

    • Patient responds "yes" to Question 4 or 5 on the C-SSRS (Children) during Screening or at any time on study.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Southwest Autism Research and Resource Center Phoenix Arizona United States 85006
    2 Phoenix Children's Hospital Phoenix Arizona United States 85016
    3 UC Davis Health System, MIND Institute Sacramento California United States 95817
    4 Children's Hospital of Colorado Denver Colorado United States 80045
    5 Emory University School of Medicine Atlanta Georgia United States 30322
    6 Rush University Medical Center Chicago Illinois United States 60612
    7 Kennedy Krieger Institute Baltimore Maryland United States 21205
    8 Boston Children's Hospital Boston Massachusetts United States 02115
    9 Fragile X Center of Atlantic Health System Morristown New Jersey United States 07960
    10 The Fragile X Spectrum Disorder Clinic at Icahn School of Medicine at Mount Sinai, Division of Medical Genetics New York New York United States 10029
    11 University of North Carolina Chapel Hill North Carolina United States 27510
    12 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    13 University Hospitals Cleveland Medical Center Cleveland Ohio United States 44106
    14 Central States Research Tulsa Oklahoma United States 74136
    15 Suburban Research Associates Media Pennsylvania United States 19063
    16 Greenwood Genetic Center Greenville South Carolina United States 29605
    17 University of Washington Center for Human Development and Disability Seattle Washington United States 98198
    18 Westmead Children's Hospital Sydney New South Wales Australia 2145
    19 Lady Cilento Children's Hospital - South Brisbane Brisbane Queensland Australia 4101
    20 Genetics Clinics Australia Melbourne Victoria Australia 3161
    21 Wellington Hospital Wellington New Zealand 6021

    Sponsors and Collaborators

    • Zynerba Pharmaceuticals, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Zynerba Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT03614663
    Other Study ID Numbers:
    • ZYN2-CL-016
    First Posted:
    Aug 3, 2018
    Last Update Posted:
    Jul 6, 2022
    Last Verified:
    Jul 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title ZYN002 - Cannabidiol Transdermal Gel Placebo Transdermal Gel
    Arm/Group Description ZYN002 supplied as a transdermal gel. Patients weighing less than or equal to 35 kg will be randomized to receive either 125 mg cannabidiol Q12H or placebo. Patients weighing greater than 35 kg will be randomized to receive 250 mg cannabidiol Q12H or placebo. ZYN002 - Cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery) Matching ZYN002 placebo supplied as a transdermal gel. Placebo Transdermal Gel: Placebo formulated as a clear gel (transdermal delivery)
    Period Title: Overall Study
    STARTED 110 102
    COMPLETED 106 99
    NOT COMPLETED 4 3

    Baseline Characteristics

    Arm/Group Title ZYN002 - Cannabidiol Transdermal Gel Placebo Transdermal Gel Total
    Arm/Group Description ZYN002 supplied as a transdermal gel. Patients weighing less than or equal to 35 kg will be randomized to receive either 125 mg cannabidiol Q12H or placebo. Patients weighing greater than 35 kg will be randomized to receive 250 mg cannabidiol Q12H or placebo. ZYN002 - cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery) Matching ZYN002 placebo supplied as a transdermal gel. Placebo Transdermal Gel: Placebo formulated as a clear gel (transdermal delivery) Total of all reporting groups
    Overall Participants 110 102 212
    Age (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    9.6
    9.8
    9.7
    Sex: Female, Male (Count of Participants)
    Female
    29
    26.4%
    24
    23.5%
    53
    25%
    Male
    81
    73.6%
    78
    76.5%
    159
    75%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    0.9%
    5
    4.9%
    6
    2.8%
    Native Hawaiian or Other Pacific Islander
    2
    1.8%
    0
    0%
    2
    0.9%
    Black or African American
    7
    6.4%
    4
    3.9%
    11
    5.2%
    White
    85
    77.3%
    81
    79.4%
    166
    78.3%
    More than one race
    6
    5.5%
    7
    6.9%
    13
    6.1%
    Unknown or Not Reported
    9
    8.2%
    5
    4.9%
    14
    6.6%
    ABC-C FXS (units on a scale) [Mean (Standard Deviation) ]
    Social Avoidance Subscale
    7.12
    (2.71)
    7.24
    (2.80)
    7.18
    (2.75)
    Irritability Subscale
    28.49
    (13.10)
    27.65
    (12.96)
    28.09
    (13.01)
    Socially Unresponsive / Lethargic
    13.42
    (6.75)
    12.82
    (7.09)
    13.13
    (6.90)

    Outcome Measures

    1. Primary Outcome
    Title Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Social Avoidance Subscale - Full Analysis Set
    Description The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is from 0 to 12, and a higher value indicates a worse outcome.
    Time Frame Change from Baseline to end of treatment (Week 12)

    Outcome Measure Data

    Analysis Population Description
    The prospective comparison of the full analytical set between ZYN002 and placebo.
    Arm/Group Title ZYN002 - Cannabidiol Transdermal Gel Placebo
    Arm/Group Description ZYN002 - Cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery) Placebo formulated as a clear gel (transdermal delivery)
    Measure Participants 109 101
    Least Squares Mean (Standard Error) [change in score]
    -2.68
    (0.310)
    -2.29
    (0.318)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection ZYN002 - Cannabidiol Transdermal Gel, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.321
    Comments
    Method MMRM - Mixed model for repeated measures
    Comments
    2. Secondary Outcome
    Title Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Irritability Subscale - Full Analysis Set
    Description The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is between 0 and 54, and the higher score means a worse outcome.
    Time Frame Change from baseline to end of treatment (Week 12)

    Outcome Measure Data

    Analysis Population Description
    The prospective comparison of the full analytical set between ZYN002 and placebo.
    Arm/Group Title ZYN002 - Cannabidiol Transdermal Gel Placebo Transdermal Gel
    Arm/Group Description ZYN002 - cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery) Placebo Transdermal Gel: Placebo formulated as a clear gel (transdermal delivery)
    Measure Participants 109 101
    Least Squares Mean (Standard Error) [Change in score]
    -5.88
    (0.960)
    -4.14
    (0.984)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection ZYN002 - Cannabidiol Transdermal Gel, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.149
    Comments
    Method MMRM - Mixed model for repeated measures
    Comments
    3. Secondary Outcome
    Title Aberrant Behavior Checklist-Community, Fragile X Factor Structure (ABC-C FXS) Socially Unresponsive/Lethargic Subscale - Full Analysis Set
    Description The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is from 0 and 39, and a higher mean indicates a worse outcome.
    Time Frame Change from baseline to end of treatment (Week 12)

    Outcome Measure Data

    Analysis Population Description
    The prospective comparison of the full analytical set between ZYN002 and placebo.
    Arm/Group Title ZYN002 - Cannabidiol Transdermal Gel Placebo Transdermal Gel
    Arm/Group Description ZYN002 - Cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery) Placebo Transdermal Gel: Placebo formulated as a clear gel (transdermal delivery)
    Measure Participants 109 101
    Least Squares Mean (Standard Error) [Change in score]
    -3.50
    (0.565)
    -3.14
    (0.577)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection ZYN002 - Cannabidiol Transdermal Gel, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.607
    Comments
    Method MMRM - Mixed model for repeated measures
    Comments
    4. Secondary Outcome
    Title Number of Participants With Any Improvement - Clinical Global Impressions- Improvement (CGI-I) - Full Analysis Set
    Description The Clinical Global Impressions- Improvement global improvement item is a 7-point Likert scale designed to measure behavioral symptomatic change at a specific time compared to baseline. CGI-I is a standard global measure of potential change with treatment in placebo-controlled pharmacotherapy trials in developmental disabilities. The score ranges form 1-very much improved to 7-very much worse. The percentage of patients with any improvement (minimally, much, very much improved) was assessed.
    Time Frame Change in CGI-I at end of treatment (Week 12)

    Outcome Measure Data

    Analysis Population Description
    The prospective comparison of the full analytical set between ZYN002 and placebo.
    Arm/Group Title ZYN002 - Cannabidiol Transdermal Gel Placebo Transdermal Gel
    Arm/Group Description ZYN002 - Cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery) Placebo Transdermal Gel: Placebo formulated as a clear gel (transdermal delivery)
    Measure Participants 109 101
    Count of Participants [Participants]
    46
    41.8%
    37
    36.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection ZYN002 - Cannabidiol Transdermal Gel, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.426
    Comments
    Method ANOVA
    Comments
    5. Primary Outcome
    Title Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Social Avoidance Subscale - Ad Hoc Analysis
    Description The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is from 0 and 12, and the higher score means a worse outcome.
    Time Frame Change from baseline to end of treatment (Week 12)

    Outcome Measure Data

    Analysis Population Description
    A pre-specified, ad hoc analysis of the data collected in patients with ≥90% methylation of the FMR1 gene to evaluate the effect of ZYN002 versus placebo was developed prior to unblinding the trial.
    Arm/Group Title ZYN002 - Cannabidiol Transdermal Gel Placebo
    Arm/Group Description ZYN002 - Cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery) Placebo formulated as a clear gel (transdermal delivery)
    Measure Participants 91 76
    Least Squares Mean (Standard Error) [Change in score]
    -2.99
    (0.323)
    -1.99
    (0.345)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection ZYN002 - Cannabidiol Transdermal Gel, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.02
    Comments
    Method MMRM - Mixed model for repeated measures
    Comments
    6. Secondary Outcome
    Title Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Irritability Subscale - Ad Hoc Analysis
    Description The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is between 0 and 54, and the higher score means a worse outcome.
    Time Frame Change from baseline in ABC-C to end of treatment (Week 12)

    Outcome Measure Data

    Analysis Population Description
    A pre-specified, ad hoc analysis of the data collected in patients with ≥90% methylation of the FMR1 gene to evaluate the effect of ZYN002 versus placebo was developed prior to unblinding the trial.
    Arm/Group Title ZYN002 - Cannabidiol Transdermal Gel Placebo Transdermal Gel
    Arm/Group Description ZYN002 - cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery) Placebo Transdermal Gel: Placebo formulated as a clear gel (transdermal delivery)
    Measure Participants 91 76
    Least Squares Mean (Standard Error) [Change in score]
    -6.43
    (1.020)
    -4.13
    (1.088)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection ZYN002 - Cannabidiol Transdermal Gel, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.091
    Comments
    Method MMRM - Mixed model for repeated measures
    Comments
    7. Secondary Outcome
    Title Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Socially Unresponsive/Lethargic Subscale - Ad Hoc Analysis
    Description The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is from 0 to 39 , and the higher score means a worse outcome.
    Time Frame Change from baseline in ABC-C to end of treatment (Week 12)

    Outcome Measure Data

    Analysis Population Description
    A pre-specified, ad hoc analysis of the data collected in patients with ≥90% methylation of the FMR1 gene to evaluate the effect of ZYN002 versus placebo was developed prior to unblinding the trial.
    Arm/Group Title ZYN002 - Cannabidiol Transdermal Gel Placebo Transdermal Gel
    Arm/Group Description ZYN002 - Cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery) Placebo Transdermal Gel: Placebo formulated as a clear gel (transdermal delivery)
    Measure Participants 91 76
    Least Squares Mean (Standard Error) [Change in score]
    -3.91
    (0.592)
    -2.74
    (0.631)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection ZYN002 - Cannabidiol Transdermal Gel, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.135
    Comments
    Method MMRM - Mixed model for repeated measures
    Comments
    8. Secondary Outcome
    Title Number of Participants With Any Improvement - Clinical Global Impressions- Improvement (CGI-I) - Ad Hoc Analysis
    Description The Clinical Global Impressions- Improvement global improvement item is a 7-point Likert scale designed to measure behavioral symptomatic change at a specific time compared to baseline. CGI-I is a standard global measure of potential change with treatment in placebo-controlled pharmacotherapy trials in developmental disabilities. The score ranges form 1-very much improved to 7-very much worse. The percentage of patients with any improvement (minimally, much, very much improved) was assessed.
    Time Frame Change in CGI-I at end of treatment (Week 12)

    Outcome Measure Data

    Analysis Population Description
    A pre-specified, ad hoc analysis of the data collected in patients with ≥90% methylation of the FMR1 gene to evaluate the effect of ZYN002 versus placebo was developed prior to unblinding the trial.
    Arm/Group Title ZYN002 - Cannabidiol Transdermal Gel Placebo Transdermal Gel
    Arm/Group Description ZYN002 - Cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery) Placebo Transdermal Gel: Placebo formulated as a clear gel (transdermal delivery)
    Measure Participants 91 76
    Count of Participants [Participants]
    43
    39.1%
    25
    24.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection ZYN002 - Cannabidiol Transdermal Gel, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.056
    Comments
    Method MMRM - Mixed model for repeated measures
    Comments

    Adverse Events

    Time Frame Adverse events were collected up to 18 weeks.
    Adverse Event Reporting Description Adverse Event Analysis Population Description: 212 patients (ZYN002: n=110; placebo: n=102) were enrolled in the study. One participant did not receive trial medication and is excluded from the safety population, resulting in 211 participants included in safety analysis (ZYN002: n=109); placebo: n=102).
    Arm/Group Title ZYN002 - Cannabidiol Transdermal Gel Placebo Transdermal Gel
    Arm/Group Description ZYN002 - Cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery) Placebo Transdermal Gel: Placebo formulated as a clear gel (transdermal delivery)
    All Cause Mortality
    ZYN002 - Cannabidiol Transdermal Gel Placebo Transdermal Gel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/109 (0%) 0/102 (0%)
    Serious Adverse Events
    ZYN002 - Cannabidiol Transdermal Gel Placebo Transdermal Gel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/109 (0%) 0/102 (0%)
    Other (Not Including Serious) Adverse Events
    ZYN002 - Cannabidiol Transdermal Gel Placebo Transdermal Gel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 45/109 (41.3%) 30/102 (29.4%)
    Gastrointestinal disorders
    vomiting 8/109 (7.3%) 9 6/102 (5.9%) 7
    General disorders
    pyrexia 5/109 (4.6%) 5 7/102 (6.9%) 7
    application site pain 7/109 (6.4%) 7 1/102 (1%) 1
    Infections and infestations
    upper respiratory tract infection 15/109 (13.8%) 16 7/102 (6.9%) 7
    nasopharyngitis 10/109 (9.2%) 10 9/102 (8.8%) 9

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Stephen O'Quinn, PharmD
    Organization Zynerba Pharmaceuticals
    Phone 919-271-1339
    Email oquinns@Zynerba.com
    Responsible Party:
    Zynerba Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT03614663
    Other Study ID Numbers:
    • ZYN2-CL-016
    First Posted:
    Aug 3, 2018
    Last Update Posted:
    Jul 6, 2022
    Last Verified:
    Jul 1, 2020