Background
Methods
Study design
Patients
Inclusion criteria | |
• Aged ≥ 18 years with a diagnosis of PDPN confirmed by a score ≥ 3 on the MNSI • HbA1c ≤ 9% (74.9 mmol/mol) at 3–6 months prior to screening and at screening | • Stable glycaemic control for ≥ 6 months prior to screening visit • Average daily pain score over the last 24 h ≥ 4 (question 5 of BPI-DN) at the screening and the baseline visit |
Exclusion criteria | |
• Primary pain associated with PDPN in the ankles or above • Significant pain (moderate or above) due to an aetiology other than PDPN • Any amputation of lower extremity • Clinically significant cardiovascular disease within 6 months prior to screening visit • Any active signs of skin inflammation around onychomycosis sites such as tenderness, redness, swelling or drainage • Body mass index ≥ 40 kg/m2 • Hypersensitivity to capsaicin any capsaicin 8% patch excipients, EMLA ingredients, or adhesives • Use of oral or transdermal opioids within 7 days preceding patch application at baseline | • Pain that could not be clearly differentiated from, or conditions that might have interfered with, the assessment of PDPN, e.g., claudication, fasciitis tendinitis and arthritis • Current or previous foot ulcer • Severe renal disease as defined by a creatinine clearance < 30 mL/min • Significant peripheral vascular diseasea • Impaired glucose tolerance only – without diabetes mellitus • Previous treatment with capsaicin 8% patch • Use of any topical pain medication on the painful areas within 7 days preceding patch application at baseline |
Safety endpoints
Primary endpoint
Norfolk QOL-DN Scale
Secondary endpoints
Secondary Norfolk QOL-DN endpoints
Utah early neuropathy scale
Sensory perception, reflex function and tolerability
Statistical methods
Results
Patient disposition
Parameter | Capsaicin 8% patch (30 min) + SOC (n = 156) | Capsaicin 8% patch (60 min) + SOC (n = 157) | SOC (n = 155) |
---|---|---|---|
Sex, n (%) | |||
Male | 74 (47.4) | 79 (50.3) | 71 (45.8) |
Female | 82 (52.6) | 78 (49.7) | 84 (54.2) |
Ethnicity, n (%) | |||
Caucasian | 154 (98.7) | 155 (98.7) | 154 (99.4) |
Other | 2 (1.3) | 2 (1.3) | 1 (0.6) |
Age, years | |||
Mean [SD] | 60.9 [10.9] | 61.0 [10.3] | 59.1 [10.3] |
Weight, kg | |||
Mean [SD] | 86.6 [14.5] | 86.7 [16.4] | 89.6 [17.6] |
Height, cm | |||
Mean [SD] | 169.7 [8.9] | 169.7 [9.0] | 169.3 [10.9] |
Body mass index, kg/m2 | |||
Mean [SD] | 30.1 [4.6] | 30.1 [5.0] | 31.2 [5.0] |
Duration of PDPN, years | |||
Mean [SD] | 4.1 [3.7] | 4.4 [3.9] | 4.4 [3.6] |
Pain medications before baseline, n (%) | |||
Overall | 70 (44.9) | 71 (45.2) | 79 (51.0) |
Analgesicsa | 56 (35.9) | 54 (34.4) | 59 (38.1) |
Antiepileptics | 44 (28.2) | 49 (31.2) | 52 (33.5) |
Psycholeptics | 22 (14.1) | 19 (12.1) | 24 (15.5) |
Anti-inflammatory/antirheumatic products | 14 (9.0) | 12 (7.6) | 17 (11.0) |
Topical joint/muscular pain productsb | 14 (9.0) | 11 (7.0) | 15 (9.7) |
Baseline average pain score (BPI-DN question 5) | |||
Mean [SD] | 5.6 [1.3] | 5.6 [1.4] | 5.5 [1.3] |
Baseline Norfolk QOL-DN score | |||
Mean [SD] | 42.8 [19.5] | 40.6 [18.3] | 41.0 [18.5] |
Baseline UENS total score | |||
Mean [SD] | 17.0 [7.4] | 16.5 [7.0] | 15.6 [6.2] |
HbA1c at screening | |||
Mean, % [SD] | 7.3 [1.0] | 7.4 [1.0] | 7.4 [1.0] |
Mean, mmol/mol [SD] | 56.6 [10.8] | 57.5 [10.8] | 57.6 [11.4] |
Pain medicationa | Capsaicin 8% patch (30 min) + SOC (n = 156) | Capsaicin 8% patch (60 min) + SOC (n = 157) | SOC (n = 155) |
---|---|---|---|
Overall, n (%) | 98 (62.8) | 105 (66.9) | 107 (69.0) |
Most commonly used category (>10 % patients in either group), n (%) | |||
Analgesicsb | 79 (50.6) | 84 (53.5) | 81 (52.3) |
Antiepileptics | 54 (34.6) | 57 (36.3) | 73 (47.1) |
Topical products for joint and muscular pain | 30 (19.2) | 35 (22.3) | 29 (18.1) |
Anti-inflammatory/antirheumatic products | 29 (18.6) | 35 (22.3) | 30 (19.4) |
Psycholeptics | 24 (15.4) | 22 (14.0) | 40 (25.8) |
Stomatological preparations | 18 (11.5) | 22 (14.0) | 18 (11.6) |
Psychoanaleptics | 16 (10.3) | 6 (3.8) | 21 (13.5) |
Ophthalmologicalsc | 15 (9.6) | 20 (12.7) | 16 (10.3) |
Most commonly used drugs (>5% patients in any group), n (%) | |||
Gabapentin | 26 (16.7) | 26 (16.6) | 35 (22.6) |
Pregabalin | 24 (15.4) | 22 (14.0) | 39 (25.2) |
Paracetamol | 23 (14.7) | 36 (22.9) | 6 (3.9) |
Tramadol | 16 (10.3) | 14 (8.9) | 6 (3.9) |
Diclofenac | 12 (7.7) | 13 (8.3) | 12 (7.7) |
Ibuprofen | 11 (7.1) | 15 (9.6) | 14 (9.0) |
Metamizole | 10 (6.4) | 10 (6.4) | 5 (3.2) |
Duloxetine | 9 (5.8) | 3 (1.9) | 10 (6.5) |
Carbamazepine | 7 (4.5) | 14 (8.9) | 10 (6.5) |
Alpha lipoic acid | 3 (1.9) | 1 (0.6) | 8 (5.2) |
Safety
Norfolk QOL-DN
Utah early neuropathy scale
Sensory perception and reflex testing
Tolerability
Event, n (%) | Capsaicin 8% patch (30 min) + SOC (n = 156) | Capsaicin 8% patch (60 min) + SOC (n = 157) | SOC (n = 155) |
---|---|---|---|
PRAEs | 105 (67.3) | 109 (69.4) | 75 (48.4) |
Mild PRAEs | 83 (53.2) | 89 (56.7) | 55 (35.5) |
Moderate PRAEs | 50 (32.1) | 54 (34.4) | 34 (21.9) |
Severe PRAEs | 19 (12.2) | 12 (7.6) | 10 (6.5) |
PRAEs identified as general disorders or administration site conditions | 54 (34.6) | 53 (33.8) | 10 (6.5) |
Application site pain | 44 (28.2) | 46 (29.3) | 0 (0) |
Mild | 23 (14.7) | 28 (17.8) | 0 (0) |
Moderate | 19 (12.2) | 16 (10.2) | 0 (0) |
Severe | 2 (1.3) | 2 (1.3) | 0 (0) |
Application site erythema | 12 (7.7) | 14 (8.9) | 0 (0) |
Mild | 12 (7.7) | 13 (8.3) | 0 (0) |
Moderate | 0 (0) | 1 (0.6) | 0 (0) |
Severe | 0 (0) | 0 (0) | 0 (0) |
PRAEs leading to permanent discontinuation | 7 (4.5) | 8 (5.1) | 3 (1.9) |
TEAEs | 104 (66.7) | 106 (67.5) | N/A |
Application site reactions | 60 (38.5) | 69 (43.9) | |
TEAEs most commonly reported (>5% of each group) | N/A | ||
Application site pain | 44 (28.2) | 46 (29.3) | |
Burning sensation | 14 (9.0) | 15 (9.6) | |
Application site erythema | 12 (7.7) | 14 (8.9) | |
Pain in extremity | 6 (3.8) | 13 (8.3) | |
TEAEs leading to permanent discontinuation | 7 (4.5) | 8 (5.1) | N/A |
Drug-relateda TEAEs | 62 (39.7) | 71 (45.2) | N/A |
Drug-relateda TEAEs leading to permanent discontinuation | 0 (0) | 4 (2.5) | N/A |
Muscle spasmsb | 0 (0) | 1 (0.6) | |
Rectal adenocarcinomac | 0 (0) | 1 (0.6) | |
Neuralgiad | 0 (0) | 1 (0.6) | |
Plantar psoriasise | 0 (0) | 1 (0.6) | |
Severe TEAEs | 19 (12.2) | 12 (7.6) | N/A |
Drug-relateda severe TEAEs | 4 (2.6) | 3 (1.9) | N/A |
Application site pain | 2 (1.3) | 2 (1.3) | |
Rectal adenocarcinomac | 0 (0) | 1 (0.6) | |
Burning sensation | 1 (0.6) | 0 (0) | |
Hypoaesthesia | 1 (0.6) | 0 (0) | |
Serious TEAEs | 20 (12.8) | 13 (8.3) | N/A |
Drug-relateda serious TEAEs | 0 (0) | 2 (1.3) | N/A |
Angina pectorisf | 0 (0) | 1 (0.6) | |
Accelerated hypertensiong | 0 (0) | 1 (0.6) | |
Rectal adenocarcinomac | 0 (0) | 1 (0.6) | |
Deaths | 1 (0.6) | 1 (0.6) | 2 (1.3) |