Evidence map›Paper›PMID 41254489›Full record

Trial reportJournal of neurodevelopmental disorders2025

Long-term safety and tolerability of transdermal cannabidiol gel in children and adolescents with Fragile X syndrome (ZYN2-CL-017): an interim analysis of an ongoing open-label extension study.

Elizabeth Berry-Kravis, Randi Hagerman, Jonathan Cohen, Dejan Budimirovic, Caroline B Buchanan, Natalie Silove, Nancy Tich, Anthony Thibodeau, Thomas Dobbins, Terri Sebree and 5 more

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of neurodevelopmental disorders, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03802799 (An Open-Label Extension Study to Assess the Long-Term Safety and Tolerability of ZYN002 Administered as a Transdermal Gel to Children, Adolescents, and Young Adults With Fragile X Syndrome), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03802799 phase2 / phase3active not recruitingnot on this map

An Open-Label Extension Study to Assess the Long-Term Safety and Tolerability of ZYN002 Administered as a Transdermal Gel to Children, Adolescents, and Young Adults With Fragile X Syndrome

TypeinterventionalSponsorZynerba Pharmaceuticals, Inc.Ran2018 to 2026Enrolled476ConditionsFragile X SyndromeArmsZYN002 - Cannabidiol Transdermal Gel
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Elizabeth Berry-KravisDepartments of Pediatrics and Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
Randi HagermanMedical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis Medical Center, Sacramento, CA, USA.
Jonathan CohenFragile X Alliance Inc, North Caulfield, Melbourne, VIC, Australia.
Dejan BudimirovicDepartments of Psychiatry and Child Psychiatry, Fragile X Clinic, Kennedy Krieger Institute/the Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Caroline B BuchananGreenwood Genetic Center, Greenville, SC, USA.
Natalie SiloveThe Children's Hospital at Westmead, Sydney, Australia.
Nancy TichHarmony Biosciences, Plymouth Meeting, PA, USA.
Anthony ThibodeauHarmony Biosciences, Plymouth Meeting, PA, USA.
Thomas DobbinsThe Griesser Group, Conshohocken, PA, USA.
Terri SebreePharmaceutical Consulting, LLC, Johnson City, TX, USA.
Stephen O'QuinnPerissos Inc, Wake Forest, NC, USA.
David S AlbersHarmony Biosciences, Plymouth Meeting, PA, USA.
Kristen G BzdekHarmony Biosciences, Plymouth Meeting, PA, USA. Publications@harmonybiosciences.com.
George NomikosHarmony Biosciences, Plymouth Meeting, PA, USA.
Kumar BudurHarmony Biosciences, Plymouth Meeting, PA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDysregulated endocannabinoid signaling is involved in Fragile X syndrome (FXS), suggesting a potential role for the endocannabinoid signaling modulator, cannabidiol, in treatment. ZYN002 is a synthetic cannabidiol that has been uniquely formulated as a gel for transdermal delivery and is currently under investigation for the treatment of behavioral symptoms associated with FXS.

designZYN2-CL-017 is an ongoing, long-term, open-label extension (OLE) safety trial of ZYN002 in patients with FXS. We are enrolling patients from past and current ZYN002 clinical trials to evaluate the safety and tolerability of ZYN002 in patients with FXS.

methodsPrimary safety assessments were conducted in patients who enrolled into the OLE from 2 completed ZYN002 trials. Secondary analyses, conducted in a subgroup enrolled from a completed placebo-controlled trial of ZYN002, included the FXS-specific Aberrant Behavior Checklist-Community Social Avoidance and Irritability subscales (ABC-C

resultsAt the time of this interim analysis data cut (January 31, 2024), 240 patients had been enrolled from 2 completed ZYN002 trials. Mean age at entry to the OLE was 9.7 years (range 3-17 years), and the majority were male (76.3%) and White (80.4%). Mean exposure to ZYN002 during the initial trials and OLE was 28 months. Treatment-related adverse events (AEs) were reported in 12.9% of patients; the most common (6.7% of patients) was short-term application site pain. The highest degree of skin irritation reported by investigators was moderate erythema in 7 patients (2.9%). In the secondary analysis cohort (n=196 evaluable patients), patients demonstrated clinically meaningful changes in ABC-C

conclusionsInterim analysis results of the ongoing OLE in children, adolescents, and young adults with FXS demonstrated that ZYN002 has a favorable long-term safety profile and is generally well tolerated. Clinically meaningful changes in behaviors from baseline continued to be observed during the OLE. These findings support further study of ZYN002 in patients with FXS.

trial registrationZYN2-CL-017 is registered on Clinicaltrials.gov (NCT03802799) on December 26, 2018.

Indexed as

CannabidiolFragile X SyndromeAdministration, CutaneousAdolescentChildChild, PreschoolFemaleGelsHumansMaleCannabidiolGelsEndocannabinoid systemFragile x syndromeIrritabilitySocial avoidanceTransdermal cannabidiol

Identifiers

PMID41254489
PMCPMC12625530

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.