Becky McCall


September 21, 2015

STOCKHOLM — Patients with diabetic peripheral neuropathy who used a capsaicin 8% patch (Qutenza, Astellas Pharma) had more relief from pain and better sleep quality than those who received a placebo patch, according to a phase 3 study reported at the European Association for the Study of Diabetes (EASD) 2015 Meeting.

The results were presented as the company announced the patch has just been approved in Europe for the additional indication of the treatment of adult diabetes patients with peripheral neuropathic pain, either alone or in combination with other medicinal products for pain.

The capsaicin patch is already approved for use in the European Union for neuropathic pain, but that license excluded patients with diabetes. Similarly, in the United States, the capsaicin patch is approved for the treatment of postherpetic neuralgia, but this label doesn't include diabetes patients.

At the EASD meeting, Malcolm Stoker, PhD, global medical lead at Astellas Pharma Global Development, the Netherlands, presented the findings of the randomized, placebo-controlled, double-blind STEP trial assessed the efficacy and safety of the patch, a dermal delivery system containing 8% capsaicin, vs placebo, following patients for 12 weeks

"We found that capsaicin 8% patch provides a statistically significant improvement in pain relief and sleep quality compared with placebo in these patients," said Dr Stoker. The capsaicin patch "was well-tolerated, and safety was consistent with previous studies in postherpetic neuralgia and HIV-associated neuropathy."

Session moderator Giel Nijpels, MD, from the Free University of Amsterdam, the Netherlands, said the researchers had done their best with blinding, given that the capsaicin patch is irritating.

Nevertheless, there was an appreciable "placebo effect," he noted, but acknowledged also that the effect of the capsaicin patch was durable, out to 12 weeks. The group has done "a good job with this study," he concluded.

Appropriate Steps Taken to Ensure Blinding

The 369 STEP participants had a mean pain duration of 5.8 years, HbA1c of 7.3%, and average daily pain score of 6.5 (Brief Pain Inventory-Diabetic Neuropathy [BPI-DN]).

They were randomized to receive one to four patches of capsaicin 8% (n=186) or placebo (n=183), as a one-off treatment, on painful regions of the feet for 30 minutes.

Each capsaicin patch is 14 cm x 20 cm (280 cm2) and consists of an adhesive side containing the active substance and an outer surface backing layer; it can be cut to the required size. The company advises that nitrile gloves should be worn at all times while handling the capsaicin patch.

In order to mitigate the irritant effect of capsaicin, all patients were treated with local anesthetic cream (lidocaine 2.5% and prilocaine 2.5%) prior to treatment, and they were told that they may or may not experience pain or burning/irritation upon application of the patch. Also, socks were put on to help hide any erythema from the patient.

"The application of capsaicin gives rise to a burning sensation, so we took [appropriate] steps to help blind the study. The physician who made the diagnosis and conducted the clinical assessments was independent from the physician or nurse responsible for application of the patch," explained Dr Stoker.

Patients were assessed in the clinic in at weeks 2, 4, 8, and 12. A total of 177 and 175 completed treatment in the active and placebo groups, respectively. The primary end point was the percentage change in average daily pain score from baseline to between weeks 2 and 8.

This is an arguably more rigorous end point than is used in many such studies, which assess pain at a discrete point in time, and sleep interference was also assessed as a secondary end point and "is critically important in this population," Dr Stoker remarked.

As well as sleep interference score and weekly sleep interference score, other secondary end points included weekly average daily pain, 30% responder rates, and daily pain score (BPI-DN). Safety and tolerability were also assessed.

The primary end-point pain score was reduced more in the capsaicin group than in the placebo group (-27.4% vs -20.9%; P = .025).

"This is a statistically significant separation of the capsaicin results from placebo, and this is sustained and in some patients greater for some weeks later, until week 12," reported Dr Stoker.

Treatment Effect Starts at 3 Weeks

The results show a treatment effect beginning a couple of weeks after application of the patch, said Dr Stoker. "The longitudinal distribution shows that the treatment groups separate clearly at week 3, starting at week 2, and this is maintained throughout the duration of the 12-week study," he noted.

Sleep was also better in those with the capsaicin patch, from baseline to between weeks 2 and 8 (P = .03) or for weeks 2 to 12 (P = .02).

In addition, greater improvements in weekly sleep interference scores were observed with capsaicin vs placebo from week 6 onward (P < .05 each week, except at week 10).

And a greater proportion of the capsaicin vs placebo group achieved at least a 30% reduction in average daily pain score between baseline and weeks 2 to 12 (40.9% vs 31.7%; P = .05).

Concerning other secondary end points, treatment satisfaction at week 12 favored the capsaicin 8% patch; a greater proportion of the capsaicin group reported being "very much improved" or "much improved"; and there were no differences in health-related quality of life between the groups, nor was there any deterioration in sharp, cold, and warm sensory perception.

In terms of safety and tolerability, 46.8% of patients in the capsaicin group experienced adverse events compared with 33.9% in the placebo group.

"The most commonly reported treatment-emergent adverse events were burning sensation [14% capsaicin, 2.7% placebo]; unsurprisingly, pain in extremity [10.8% vs 5.5%]; and application-site pain. There were no serious adverse events or deaths in either group," Dr Stoker reported.

In conclusion, he added that the study extends the range of peripheral neuropathic pain etiologies for which the capsaicin 8% patch shows efficacy and safety.

The study was supported by Astellas Pharma Europe. Dr Stoker is an employee of Astellas Pharma Global Development, the Netherlands. Dr Nijpels has declared no relevant financial relationships.

European Association for the Study of Diabetes 2015 Meeting; Stockholm, Sweden. Abstract 64, presented September 15, 2015.


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