P-057 - (Poster #57) Comparing the Impact of the High-Concentration Capsaicin Topical System (HCCTS) on Pain and Sleep in Patients with Painful Diabetic Peripheral Neuropathy (PDPN): Findings from the STEP Randomized Trial and the Real-World CASPAR Study

Chronic pain develops in 30% to 50% of people with diabetic peripheral neuropathy (DPN).^1-3 PDPN of the feet can be particularly debilitating, interfering with daily activities, causing disability and psychosocial impairment, and affecting sleep, ability to work, affective distress, and quality of life (QOL).⁴ While randomized, controlled trials are the “gold standard” trial design for evaluating the efficacy and safety of new therapeutic agents, real-world evidence studies can provide insight into real-world treatment patterns and reflect a broader, more diverse patient population that is more representative of patients seen in regular clinical practice.^5,6

Purpose/Objectives:

Results from the STEP randomized, double-blind trial and the CASPAR registry study were compared to evaluate whether HCCTS treatment of patients with PDPN of the feet produced similar improvements in pain intensity and sleep in a real-world clinical practice setting as it did in a controlled clinical trial setting.

Methods:

STEP⁷ was a 12-week, phase 3, randomized, double-blind, placebo-controlled trial conducted in adult patients with PDPN of the feet at 29 centers in the United States between February 2012 and February 2014. The primary objective of the STEP trial was to evaluate the efficacy of a single 30-minute application of HCCTS compared to a placebo patch in reducing 24-hour average pain intensity (API) (as assessed by question 5 of the Brief Pain Inventory-Diabetic Neuropathy) in patients with PDPN of the feet. Improvement in sleep interference was a secondary objective.

In comparison, CASPAR, a non-interventional, retrospective cohort study, used data from the German Pain e-registry (283 pain centers) to assess 24-hour API (VAS 0-100 mm) and sleep impairment (sleep item of the modified pain disability index [mPDI]) in a cohort of patients with PDPN of the feet after ≥1 HCCTS applications (~3-month intervals) over a 12-month period. QOL,  using the Veterans RAND-12 (VR-12), and affective distress,  using the Depression, Anxiety and Stress Scale (DASS-21), were also assessed.

Results:

In the STEP trial, a total of 369 patients with PDPN of the feet were randomized to receive one 30-minute application of either HCCTS (n=186) or placebo patch (n=183). In the CASPAR study, the analysis included a total of 365 patients with PDPN of the feet, including 94, 88, 75, and 108 patients who received one, two, three, or four 30-minute HCCTS applications, respectively, over a 12-month period. Patients in the CASPAR study were slightly older than those in the STEP trial (66.1 vs 63.0 years, respectively), and pain duration was shorter (4.6 vs 5.8 years, respectively).

In the STEP trial, the percentage reduction in 24-hour API from baseline to Weeks 2-8 was statistically significant for HCCTS versus placebo (-27.4% vs -20.9%, P=0.025); improvements in pain were observed from week 2 onward. Improvements in sleep interference scores from baseline to Weeks 2-12 (-34.0% vs -24.7% for HCCTS and placebo, respectively; P=0.020) were also observed.

In the CASPAR study, by Month 3 (after one treatment), 24-hour API was reduced by -26.6%, -27.5%, -34.7%, and -32.2% for cohorts who received, over the 12-month observation period, one, two, three, or four HCCTS treatments, respectively (P< 0.001 vs baseline). Furthermore, 24-hour API continued to decrease with ongoing treatment, with patients who received four applications achieving API reductions of -32.2%, -56.8%, -73.6%, -85.7% at Months 3, 6, 9, and 12 months, respectively. When HCCTS treatment was discontinued, API began to increase. A similar pattern of improvement in sleep quality with HCCTS treatment was observed in the four-treatment cohort, with average sleep interference score (mPDI-6, mm VAS) percent changes from baseline of -31.4%, -36.0%, -73.3%, -84.4% after one, two, three, and four HCCTS applications, respectively (P< 0.001 for all).

In both studies, tolerability was consistent with the known HCCTS profile, with the most common treatment-emergent adverse events being transient application-site reactions.

In the CASPAR study, use of concomitant pain medication for neuropathic pain decreased as HCCTS treatment continued, and 34.0% of patients who received four HCCTS treatments were able to stop all concomitant medication for PDPN 12 months after their initial treatment.

Conclusions/Implications for future research and/or clinical care: For patients with PDPN of the feet, one HCCTS treatment yielded comparable pain relief and improvement in sleep quality in both the STEP randomized, controlled trial and the CASPAR real-world study. Furthermore, the real-world CASPAR study highlights the effectiveness of repeat HCCTS treatment in patients with PDPN of the feet, demonstrating significant reductions in pain intensity and improvement in sleep quality over 12 months, with the biggest improvements for patients who received four treatments. No new safety issues were observed in either study, with the most common adverse events being transient application-site reactions.