Clinical Trials

Date: 2017-08-14

Type of information: Results

phase: 2

Announcement: results

Company: Zynerba Pharmaceuticals (USA - PA)

Product: ZYN002 CBD gel

Action mechanism: cannabidiol . ZYN002 CBD gel is a synthetic cannabidiol  that is formulated as a patent-protected permeation-enhanced gel. It is designed to provide consistent, controlled drug delivery transdermally with convenient twice-daily dosing. Transdermal therapeutics are absorbed through the skin directly into the systemic circulation, avoiding first-pass liver metabolism and potentially enabling lower dosage levels of active pharmaceutical ingredients and rapid and reliable absorption with high bioavailability. In addition, transdermal delivery avoids the gastrointestinal tract and potential stomach acid degradation of CBD into THC (associated with psychoactive effects), as demonstrated in a Zynerba in vitro study.

Disease: knee pain due to osteoarthritis

Therapeutic area: Rheumatic diseases - Inflammatory diseases

Country:

Trial details: The STOP clinical trial is a Phase 2 multi-center, double-blind, placebo-controlled, multi-dose clinical trial designed to evaluate the efficacy and safety of ZYN002 in patients with knee pain due to OA. Up to 300 patients will be enrolled in the clinical trial and will be followed for two weeks during a baseline phase, which includes a one-week washout period. After completion of the baseline phase, patients will be randomized 1:1:1 to receive either 250 mg of ZYN002 4.2% CBD gel every 12 hours, 125 mg of ZYN002 4.2% CBD gel every 12 hours or placebo gel every 12 hours for 12 weeks. The primary endpoint of the study is the change from baseline in the weekly mean of the 24-hour average worst pain score.

Latest news:

• • On August 14, 2017, Zynerba Pharmaceuticals reported top line results from its Phase 2 STOP (Synthetic Transdermal Cannabidiol for Treatment of Knee Pain due to Osteoarthritis) clinical trial evaluating ZYN002 (cannabidiol [CBD] gel). The study did not meet its primary endpoint of reduction from baseline in the weekly mean of the 24-hour average worst pain score at week 12 for either dose. However, statistically significant results were achieved for a number of secondary endpoints. Importantly, the composite responder analysis (defined as a ?30 percent reduction in worst average daily pain scores and a ?20 percent improvement in the WOMAC physical function score) for 250 mg daily of ZYN002 4.2% CBD gel achieved statistical significance (p=0.016). A trend toward statistical significance was observed in other secondary endpoints.
• Three hundred and twenty (320) patients aged 41 to 78 years of age with confirmed osteoarthritis of the knee were randomized in the double-blind, multi-center STOP trial. Patients who completed the one-week washout and the seven-to-10-day baseline phase were randomized 1:1:1 to receive either 250 mg of ZYN002 4.2% CBD gel daily, 500 mg of ZYN002 daily, or placebo, for 12 weeks. Enrolled patients had a mean worst knee pain score of 6.9 on a scale of 1 to 10 during baseline.
• Primary Endpoint Data: Across all participants, patients on 250 mg of ZYN002 daily achieved a 2.64 mean reduction from baseline in average worst knee pain scores at week 12; patients on 500 mg of ZYN002 daily achieved a 2.83 mean reduction from baseline in average worst knee pain scores at week 12; and patients on placebo achieved a 2.37 mean reduction from baseline in average worst knee pain scores at week 12. These results were not statistically significant. Secondary Endpoint Data: Statistically significant results were achieved for a number of key secondary endpoints, including the composite responder analysis for 250 mg of ZYN002 daily (p=0.016), and the responder rate based on ?30% reduction in worst pain severity at week 8 for 250 mg of ZYN002 daily (p=0.037). A trend toward statistical significance was observed in other secondary endpoints. Post Hoc Analysis (Gender): Men on 250 mg of ZYN002 daily achieved a 1.65 mean reduction from baseline in average worst knee pain scores at week 4 compared to a 1.19 mean reduction from baseline in men on placebo (p=0.156); a 2.30 mean reduction from baseline in average worst knee pain scores at week 8 compared to a 1.56 mean reduction from baseline in men on placebo (p=0.066); and a 2.68 mean reduction from baseline in average worst knee pain scores at week 12 compared to a 1.70 mean reduction from baseline in men on placebo (p=0.049). Females had a higher placebo rate and did not achieve significance in the endpoint. Post Hoc Analysis (Pain Severity): In an evaluation of patients with a baseline pain score of ?7, there were 101 patients on ZYN002 and 48 patients in the placebo arm at baseline. Patients on ZYN002 achieved a 2.17 mean reduction from baseline in average worst knee pain scores at week 4 compared to a 1.6 mean reduction from baseline in patients on placebo (p=0.029); a 3.02 mean reduction from baseline in average worst knee pain scores at week 8 compared to a 2.22 mean reduction from baseline in patients on placebo (p=0.054); and a 3.29 mean reduction from baseline in average worst knee pain scores at week 12 compared to a 2.52 mean reduction from baseline in patients on placebo (p=0.086). Safety Data: ZYN002 was shown to be very well tolerated and the safety profile was consistent with previously released data from clinical trials. Of the patients in the safety database, 50% (n=106) of the patients on ZYN002 had at least one treatment emergent adverse event, compared to 42% (n=45) of patients on placebo. There were only two treatment emergent/treatment related adverse events that exceeded 3% of the patients on ZYN002 and were greater than placebo: application site dryness (3.8%, n=8; placebo 0.9%, n=1) and headache (3.3%, n=7; placebo 1.9%, n=2). There was one (0.5%) treatment related serious adverse event on ZYN002 and three (2.8%) treatment related serious adverse events reported on placebo. Discontinuation from the study was 22.5% (n=48) for patients on ZYN002 and 33.6% (n=36) for patients on placebo. There were twelve (5.6%) patients that discontinued due to adverse events on ZYN002 and 8 (7.5%) that discontinued due to adverse events on placebo. Pharmacokinetic Data: ZYN002 500 mg and 250 mg daily dose median plasma concentrations were dose proportional, with the 500 mg dose levels being approximately two times the plasma concentration of the 250 mg dose.
• • On March 13, 2017, Zynerba Pharmaceuticals announced that it has completed enrollment in  the Phase 2 STOP (Synthetic Transdermal Cannabidiol for the Treatment of Knee Pain due to Osteoarthritis) clinical trial evaluating ZYN002 CBD gel for the treatment of osteoarthritis. In this trial, 418 patients with osteoarthritis knee pain were screened and the company has already exceeded the target of randomizing 300 patients. Additional patients still in the baseline period are expected to be randomized as well and the screen failure rate experienced for this trial has been between 20% – 25%. The primary endpoint for the STOP trial will assess the change from baseline in the weekly mean of the 24-hour average of worst pain score.
• • On September 6, 2016, Zynerba Pharmaceuticals announced that it has initiated a Phase 2 clinical trial, STOP (Synthetic Transdermal Cannabidiol for the Treatment of Knee Pain due to Osteoarthritis (OA)), of ZYN002 cannabidiol (CBD) gel.  The company expects to report topline results in the first half of 2017.

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