Capsaicin 8% patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy: a randomised, 52-week, open-label, safety study

Abstract

Background: This 52-week study evaluated the long-term safety and tolerability of capsaicin 8% w/w (179 mg) patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy (PDPN).

Methods: Phase 3, multinational, open-label, randomised, controlled, 52-week safety study, conducted in Europe. Patients were randomised to capsaicin 8% patch repeat treatment (30 or 60 min; 1-7 treatments with ≥ 8-week intervals) to painful areas of the feet plus SOC, or SOC alone. The primary objective was the safety of capsaicin 8% patch repeat treatment (30 min and 60 min applications) plus SOC versus SOC alone over 52 weeks, assessed by changes in Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) total score from baseline to end of study (EOS). Secondary safety endpoints included Utah Early Neuropathy Scale (UENS) assessments and standardised testing of sensory perception and reflex function.

Results: Overall, 468 patients were randomised (30 min plus SOC, n = 156; 60 min plus SOC, n = 157; SOC alone, n = 155). By EoS, mean changes in Norfolk QOL-DN total score from baseline [estimated mean difference versus SOC alone; 90% CI for difference] were: 30 min plus SOC, -27.6% [-20.9; -31.7, -10.1]; 60 min plus SOC, -32.8% [-26.1; -36.8, -15.4]; SOC alone, -6.7%. Mean changes [difference versus SOC alone] in UENS total score by EoS versus baseline were: 30 min plus SOC, -2.1 [-0.9; -1.8, 0.1]; 60 min plus SOC, -3.0 [-1.7; -2.7, -0.8]; SOC alone, -1.2. No detrimental deterioration was observed in any of the Norfolk or UENS subscales by EoS with capsaicin. Also, no worsening in sensory perception testing of sharp, warm, cold and vibration stimuli was found with capsaicin by EoS. Capsaicin treatment was well tolerated and the most frequent treatment-emergent adverse events were application site pain (30 min, 28.2%; 60 min, 29.3%), burning sensation (30 min, 9.0%; 60 min, 9.6%) and application site erythema (30 min, 7.7%; 60 min, 8.9%).

Conclusion: In patients with PDPN, capsaicin 8% patch repeat treatment plus SOC over 52 weeks was well tolerated with no negative functional or neurological effects compared with SOC alone.

Trial registration: ClinicalTrials.gov registration: NCT01478607 . Date of registration November 21, 2011; retrospectively registered.

Keywords: Capsaicin 8% patch; Norfolk QOL-DN; Painful diabetic peripheral neuropathy; TPRV1; UENS.

Figures

Fig. 1

Study design *Capsaicin 8% patch treatment (Groups 1 and 2) took place at scheduled bi-monthly visits (P) or unscheduled visit at intervals of at least 8 weeks. EoS visit for Groups 1 and 2 took place between 8 and 12 weeks after last patch application if patch was applied at Visit 8 (Month 12) and between Week 52 and 56 for patients without a patch application at Visit 8 (Month 12). EoS visit for Group 3 took place between Week 52 and 56. EoS end of study, SOC standard of care, UENS Utah Early Neuropathy Scale

Fig. 2

Category shift schema from baseline to EoS. EoS end of study

Fig. 3

Patient flow. AE adverse event, SOC standard of care

Fig. 4

Mean percentage change from baseline to end of study in Norfolk QOL-DN scores (LOCF) (SAS) Treatment group comparisons are least squares mean difference [90% CI]. CI confidence interval, LOCF last observation carried forward, SAS safety analysis set, SOC standard of care

Fig. 5

Mean percentage change in Norfolk QOL-DN total score from baseline during the study (SAS) In patients who received a capsaicin treatment at Month 12 and had an end of study visit at Month 14, mean [SD] change in Norfolk total score by Month 14 was: 30 min, −36.1% [51.6] (n = 79); 60 min, −40.2% [39.4] (n = 76). SAS safety analysis set, SOC standard of care

Fig. 6

Mean change in UENS total and subscale scores from baseline to EoS (LOCF) (SAS) Treatment group comparisons are least squares mean difference [90% CI]. CI confidence interval, EoS end of study, LOCF last observation carried forward, SAS safety analysis set, SOC standard of care

Fig. 7

Proportion of patients reporting improved, unchanged, or worsened sensory or reflex function by EoS (SAS) C30 + SOC, capsaicin 8% patch (30 min) + SOC (n = 150); C60 + SOC, capsaicin 8% patch (60 min) + SOC (n = 146) EoS end of study, SAS safety analysis set, SOC standard of care (n = 143); n is number of patients with non-missing data

Fig. 8

a and b Change in proportion of patients reporting sensory and reflex testing from baseline to EoS (SAS) C30 + SOC, capsaicin 8% patch (30 min) + SOC (n = 156); C60 + SOC, capsaicin 8% patch (60 min) + SOC (n = 157) EoS end of study, SAS safety analysis set, SOC standard of care (n = 155)