Cannabidiol gel for osteoarthritis knee pain gives lukewarm results

LIVERPOOL, ENGLAND – There was no significant reduction in pain from knee osteoarthritis (OA) with the use of investigational cannabidiol (CBD) gel ZYN002 in a phase 2a trial presented at the World Congress on Osteoarthritis.

The mean reductions in baseline knee pain scores from study entry to a 12-week assessment were –2.4 for placebo and –2.6 (P = .5) and –2.8 (P = .25), respectively, for a 250-mg and a 500-mg formulation of the gel.

Sara Freeman/MDedge

While there was a trend for benefit, it was “neither statistically or clinically significant,” reported David Hunter, MBBS, PhD.

However, he observed that a significantly (P = .016) greater number of patients who received the 250-mg dose (52.7%) were “composite responders,” compared with patients who received placebo (34.1%). A composite response was defined as at least a 30% reduction in pain, and a 20% decrease in WOMAC physical function subscale score at the last observation.

Although the percentage of composite responders was also higher than placebo with the 500-mg dose, the difference wasn’t significant (45.1% vs. 34.1%; P = .0169).

Post-hoc analyses also suggested that perhaps some patients may benefit more than others, reported Dr. Hunter, professor of medicine at the University of Sydney and the Royal North Shore Hospital, Sydney.

For example, patients with baseline pain scores or 7 or more had greater mean reduction in pain at 12 weeks with both doses of the gel combined than placebo at week 4 (–2.2 vs. –1.6; P = .029), although the difference was not significant at week 8 (–3.0 vs. –2.2; P = .05) or 12 (–3.3 vs. –2.5; P = .086).

 

Women also exhibited a greater placebo response than did men, and “patients with less variability in baseline pain scores may have had greater separation between placebo and the treatment,” Dr. Hunter said. Indeed, 50%-52% of patients with less than 33% variation in baseline scores had a composite response to the gel, versus 27% for the placebo arm.

Evidence from preclinical models suggest that cannabinoids have antinociceptive and antihyperalgesic effects, Dr. Hunter explained at the congress, sponsored by the Osteoarthritis Research Society International. CBD has also been shown to have broad anti-inflammatory effects, and it may even promote osteoclast cell function and decrease bone resorption.

ZYN002 is a synthetic CBD formulated for transdermal delivery using a patented method to enhance its permeation through the skin. According to the manufacturer, Zynerba, it was developed for neuropsychiatric disorders, including fragile X syndrome, adult refractory epilepsy, and developmental and epileptic encephalopathies.

 

The primary aim of the phase 2 trial reported by Dr. Hunter was to assess ZYN002’s efficacy in managing osteoarthritis knee pain. Secondary objectives were to assess the gel’s safety and tolerability.

The STOP 1 (Synthetic Transdermal Cannabidiol for the Treatment of Knee Pain Due to Osteoarthritis) trial was a double-blind, placebo-controlled trial. For inclusion in the study, patients had to be between age 40 and 75 years and have had knee pain for at least 12 months because of primary OA, based on clinical and x-ray data as per American College of Rheumatology criteria. Anyone with a history of fibromyalgia or epilepsy was excluded.

A total of 320 patients with painful knee OA, with a mean age of 62 years, were randomized and underwent a 1-week washout period in which all their analgesic medications being used for osteoarthritis knee pain, except acetaminophen, were stopped. That was followed by a 7- to 10-day period when baseline daily worst pain levels were captured using a 0-10 numeric rating scale. Patients then underwent 12 weeks of treatment with either a high (500 mg) or a low (250 mg) dose of the gel, or placebo, given in twice-daily doses.

 

Just over a third (34%) of patients in the placebo arm discontinued the study, compared with 22% and 24% of those in the high- and low-dose gel arms. The main reason for discontinuation was withdrawn consent because of lack of efficacy in the placebo arm, with 8%, 8%, and 4% of patients, respectively, discontinuing because of adverse effects.

“Treatment-emergent adverse effects were roughly equally distributed across the three groups,” Dr. Hunter reported. The adverse events of more interest, he noted, were application site dryness, reaction, or pain. There was “a slight predisposition” to each of these in the 250-mg gel arm (5%, 3%, and 3% of patients affected) versus the 500-mg gel (3%, 0%, and 0%) and placebo (1%, 1%, 0%) arms.

SOURCE: Hunter D et al. Osteoarthritis Cartilage 2018:26(1):S26. Abstract 30.

LIVERPOOL, ENGLAND – There was no significant reduction in pain from knee osteoarthritis (OA) with the use of investigational cannabidiol (CBD) gel ZYN002 in a phase 2a trial presented at the World Congress on Osteoarthritis.

The mean reductions in baseline knee pain scores from study entry to a 12-week assessment were –2.4 for placebo and –2.6 (P = .5) and –2.8 (P = .25), respectively, for a 250-mg and a 500-mg formulation of the gel.

Sara Freeman/MDedge

While there was a trend for benefit, it was “neither statistically or clinically significant,” reported David Hunter, MBBS, PhD.

However, he observed that a significantly (P = .016) greater number of patients who received the 250-mg dose (52.7%) were “composite responders,” compared with patients who received placebo (34.1%). A composite response was defined as at least a 30% reduction in pain, and a 20% decrease in WOMAC physical function subscale score at the last observation.

Although the percentage of composite responders was also higher than placebo with the 500-mg dose, the difference wasn’t significant (45.1% vs. 34.1%; P = .0169).

Post-hoc analyses also suggested that perhaps some patients may benefit more than others, reported Dr. Hunter, professor of medicine at the University of Sydney and the Royal North Shore Hospital, Sydney.

For example, patients with baseline pain scores or 7 or more had greater mean reduction in pain at 12 weeks with both doses of the gel combined than placebo at week 4 (–2.2 vs. –1.6; P = .029), although the difference was not significant at week 8 (–3.0 vs. –2.2; P = .05) or 12 (–3.3 vs. –2.5; P = .086).

 

Women also exhibited a greater placebo response than did men, and “patients with less variability in baseline pain scores may have had greater separation between placebo and the treatment,” Dr. Hunter said. Indeed, 50%-52% of patients with less than 33% variation in baseline scores had a composite response to the gel, versus 27% for the placebo arm.

Evidence from preclinical models suggest that cannabinoids have antinociceptive and antihyperalgesic effects, Dr. Hunter explained at the congress, sponsored by the Osteoarthritis Research Society International. CBD has also been shown to have broad anti-inflammatory effects, and it may even promote osteoclast cell function and decrease bone resorption.

ZYN002 is a synthetic CBD formulated for transdermal delivery using a patented method to enhance its permeation through the skin. According to the manufacturer, Zynerba, it was developed for neuropsychiatric disorders, including fragile X syndrome, adult refractory epilepsy, and developmental and epileptic encephalopathies.

 

The primary aim of the phase 2 trial reported by Dr. Hunter was to assess ZYN002’s efficacy in managing osteoarthritis knee pain. Secondary objectives were to assess the gel’s safety and tolerability.

The STOP 1 (Synthetic Transdermal Cannabidiol for the Treatment of Knee Pain Due to Osteoarthritis) trial was a double-blind, placebo-controlled trial. For inclusion in the study, patients had to be between age 40 and 75 years and have had knee pain for at least 12 months because of primary OA, based on clinical and x-ray data as per American College of Rheumatology criteria. Anyone with a history of fibromyalgia or epilepsy was excluded.

A total of 320 patients with painful knee OA, with a mean age of 62 years, were randomized and underwent a 1-week washout period in which all their analgesic medications being used for osteoarthritis knee pain, except acetaminophen, were stopped. That was followed by a 7- to 10-day period when baseline daily worst pain levels were captured using a 0-10 numeric rating scale. Patients then underwent 12 weeks of treatment with either a high (500 mg) or a low (250 mg) dose of the gel, or placebo, given in twice-daily doses.

 

Just over a third (34%) of patients in the placebo arm discontinued the study, compared with 22% and 24% of those in the high- and low-dose gel arms. The main reason for discontinuation was withdrawn consent because of lack of efficacy in the placebo arm, with 8%, 8%, and 4% of patients, respectively, discontinuing because of adverse effects.

“Treatment-emergent adverse effects were roughly equally distributed across the three groups,” Dr. Hunter reported. The adverse events of more interest, he noted, were application site dryness, reaction, or pain. There was “a slight predisposition” to each of these in the 250-mg gel arm (5%, 3%, and 3% of patients affected) versus the 500-mg gel (3%, 0%, and 0%) and placebo (1%, 1%, 0%) arms.

SOURCE: Hunter D et al. Osteoarthritis Cartilage 2018:26(1):S26. Abstract 30.

LIVERPOOL, ENGLAND – There was no significant reduction in pain from knee osteoarthritis (OA) with the use of investigational cannabidiol (CBD) gel ZYN002 in a phase 2a trial presented at the World Congress on Osteoarthritis.

The mean reductions in baseline knee pain scores from study entry to a 12-week assessment were –2.4 for placebo and –2.6 (P = .5) and –2.8 (P = .25), respectively, for a 250-mg and a 500-mg formulation of the gel.

Sara Freeman/MDedge

While there was a trend for benefit, it was “neither statistically or clinically significant,” reported David Hunter, MBBS, PhD.

However, he observed that a significantly (P = .016) greater number of patients who received the 250-mg dose (52.7%) were “composite responders,” compared with patients who received placebo (34.1%). A composite response was defined as at least a 30% reduction in pain, and a 20% decrease in WOMAC physical function subscale score at the last observation.

Although the percentage of composite responders was also higher than placebo with the 500-mg dose, the difference wasn’t significant (45.1% vs. 34.1%; P = .0169).

Post-hoc analyses also suggested that perhaps some patients may benefit more than others, reported Dr. Hunter, professor of medicine at the University of Sydney and the Royal North Shore Hospital, Sydney.

For example, patients with baseline pain scores or 7 or more had greater mean reduction in pain at 12 weeks with both doses of the gel combined than placebo at week 4 (–2.2 vs. –1.6; P = .029), although the difference was not significant at week 8 (–3.0 vs. –2.2; P = .05) or 12 (–3.3 vs. –2.5; P = .086).

 

Women also exhibited a greater placebo response than did men, and “patients with less variability in baseline pain scores may have had greater separation between placebo and the treatment,” Dr. Hunter said. Indeed, 50%-52% of patients with less than 33% variation in baseline scores had a composite response to the gel, versus 27% for the placebo arm.

Evidence from preclinical models suggest that cannabinoids have antinociceptive and antihyperalgesic effects, Dr. Hunter explained at the congress, sponsored by the Osteoarthritis Research Society International. CBD has also been shown to have broad anti-inflammatory effects, and it may even promote osteoclast cell function and decrease bone resorption.

ZYN002 is a synthetic CBD formulated for transdermal delivery using a patented method to enhance its permeation through the skin. According to the manufacturer, Zynerba, it was developed for neuropsychiatric disorders, including fragile X syndrome, adult refractory epilepsy, and developmental and epileptic encephalopathies.

 

The primary aim of the phase 2 trial reported by Dr. Hunter was to assess ZYN002’s efficacy in managing osteoarthritis knee pain. Secondary objectives were to assess the gel’s safety and tolerability.

The STOP 1 (Synthetic Transdermal Cannabidiol for the Treatment of Knee Pain Due to Osteoarthritis) trial was a double-blind, placebo-controlled trial. For inclusion in the study, patients had to be between age 40 and 75 years and have had knee pain for at least 12 months because of primary OA, based on clinical and x-ray data as per American College of Rheumatology criteria. Anyone with a history of fibromyalgia or epilepsy was excluded.

A total of 320 patients with painful knee OA, with a mean age of 62 years, were randomized and underwent a 1-week washout period in which all their analgesic medications being used for osteoarthritis knee pain, except acetaminophen, were stopped. That was followed by a 7- to 10-day period when baseline daily worst pain levels were captured using a 0-10 numeric rating scale. Patients then underwent 12 weeks of treatment with either a high (500 mg) or a low (250 mg) dose of the gel, or placebo, given in twice-daily doses.

 

Just over a third (34%) of patients in the placebo arm discontinued the study, compared with 22% and 24% of those in the high- and low-dose gel arms. The main reason for discontinuation was withdrawn consent because of lack of efficacy in the placebo arm, with 8%, 8%, and 4% of patients, respectively, discontinuing because of adverse effects.

“Treatment-emergent adverse effects were roughly equally distributed across the three groups,” Dr. Hunter reported. The adverse events of more interest, he noted, were application site dryness, reaction, or pain. There was “a slight predisposition” to each of these in the 250-mg gel arm (5%, 3%, and 3% of patients affected) versus the 500-mg gel (3%, 0%, and 0%) and placebo (1%, 1%, 0%) arms.

SOURCE: Hunter D et al. Osteoarthritis Cartilage 2018:26(1):S26. Abstract 30.