A Study to Evaluate Efficacy and Safety of a Single Application of Capsaicin 8%Transdermal Delivery System Compared to Placebo in Reducing Pain Intensity in Subjects With Painful Diabetic Peripheral Neuropathy (PDPN)

Participants were divided into 2 groups of approximately equal size. In the first group,
participants received a Capsaicin 8% patch applied for 30 minutes to the feet; in the second
group, participants received a placebo patch applied for 30 minutes to the feet.
Participants were involved in the study for approximately 12 weeks and have visited the
clinic approximately 6 times.

Inclusion Criteria:

- Diagnosis of painful, distal, symmetrical, sensorimotor polyneuropathy which is due
to diabetes, for at least 1 year prior to screening visit

- Average Numeric Pain Rating Scale (NPRS) score over the last 24 hours of ≥4 at the
screening and the baseline visit

Exclusion Criteria:

- Primary pain associated with PDPN (Painful Diabetic Peripheral Neuropathy) in the
ankles or above

- Pain that could not be clearly differentiated from, or conditions that might
interfere with the assessment of PDPN (Painful Diabetic Peripheral Neuropathy),
neurological disorders unrelated to diabetic neuropathy (e.g., phantom limb pain from
amputation); skin condition in the area of the neuropathy that could alter sensation
(e.g., plantar ulcer)

- Current or previous foot ulcer as determined by medical history and medical
examination

- Any amputation of lower extremity

- Severe renal disease as defined by a creatinine clearance of <30 ml/min calculated
according to the Cockcroft-Gault formula

- Clinically significant cardiovascular disease within 6 months prior to screening
visit defined as cerebrovascular accident, unstable or poorly controlled
hypertension, transient ischemic attack, myocardial infarction, unstable angina,
current arrhythmia, any heart surgery including coronary artery bypass graft surgery,
percutaneous coronary angioplasty/stent placement, or valvular heart disease

- Significant peripheral vascular disease (intermittent claudication or lack of
pulsation of either the dorsalis pedis or posterior tibial artery, or ankle-brachial
systolic blood pressure index of <0.80)

- Clinically significant foot deformities, including hallux rigidus, hallux valgus, or
rigid toe as determined by physical examination as judged by the investigator

- Clinically significant ongoing, uncontrolled or untreated abnormalities in cardiac,
renal, hepatic, or pulmonary function that may interfere either with the ability to
complete the study or the evaluation of adverse events

- Diagnosis of any poorly controlled major psychiatric disorder

- Active substance abuse or history of chronic substance abuse within 1 year prior to
screening visit or any prior chronic substance abuse (including alcoholism) likely to
re-occur during the study period as judged by the investigator

- Hypersensitivity to capsaicin (i.e., chili peppers or over-the-counter [OTC]
capsaicin products), any Capsaicin 8% transdermal delivery system excipients,
Eutectic Mixture of Local Anaesthetics (EMLA) ingredients or adhesives

- Use of any topical pain medication, such as non-steroidal anti-inflammatory drugs,
menthol, methyl salicylate, local anesthetics, steroids or capsaicin products on the
painful areas within 7 days preceding the first patch application at the baseline
visit

- Use of oral or transdermal opioids exceeding a total daily dose of morphine of 80
mg/day, or equivalent; or any parenteral opioids, regardless of dose, within 7 days
preceding the first patch application at the baseline visit

- Skin areas to be treated with Capsaicin 8% transdermal delivery system showing
changes such as crusting or ulcers

- Planned elective surgery during the trial