Safety and Effectiveness of Repeated Administration of QUTENZA Patches for Treatment of Pain Caused by Nerve Damage

The rationale for the current study is to evaluate the safety of repeated QUTENZA applications, including the effect of QUTENZA on sensory function in subjects diagnosed with different types of Peripheral Neuropathic Pain (PNP). In order to adequately assess the long-term safety QUTENZA in well defined patient populations the current study will enroll a minimum of 100 patients each with HIV-Associated Neuropathy (HIV-AN) and Postherpetic Neuralgia (PHN).

Common Inclusion Criteria:

• Be in good health as determined by the investigator
• Average pain score >=4 during screening period (using the average reported pain from the Brief Pain Inventory [BPI])
• Intact, non-irritated, dry skin over the painful area(s) to be treated
• All females of child bearing potential must be willing to use effective methods of birth control during the study and for 30 days following study termination
• Be willing and able to comply with protocol requirements for the duration of study participation

Population-specific Inclusion Criteria:

• All subjects must meet one (and only one) of the Population-Specific Inclusion Criteria for PHN, HIV-AN, PNI or ISNN or have adequately characterized PNP based on clinical history and examination.

• Postherpetic Neuralgia (PHN): Prior diagnosis of PHN with pain persisting at least 3 months since shingles vesicle crusting, documented by the primary treating physician or investigator
• Or

• Painful HIV-Associated Neuropathy (HIV-AN): Presence of HIV-AN existing for a minimum of 3 months, confirmed using the Brief Peripheral Neuropathy Screen (BPNS) at the time of study entry
• Or

• Peripheral Neuropathic Injury (PNI): Diagnosis of Post-traumatic Peripheral Neuropathic Pain syndrome, including post-surgical neuropathic pain, neuropathic pain due to peripheral nerve injury, confirmed by a qualified pain specialist and persisting for a minimum of 3 months following the traumatic event
• Or

• Idiopathic Small Nerve Neuropathy (ISNN): Diagnosis of ISNN based on clinical criteria (e.g. quantitative sensory testing) or skin biopsy

• Neuropathy exclusively or predominantly affecting A-δ (small myelinated) and nociceptive C (unmyelinated) nerve fibres
• Loss of pinprick and temperature sensation in feet
• Or

• Other Peripheral Neuropathic Pain (PNP): Adequately characterized PNP based on clinical history and examination existing at the time of screening

Exclusion criteria

• Any prior receipt of QUTENZA open label or blinded study patches
• 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 visit
• Lack of an effective pain medication strategy for the subject, such as unwillingness to use opioid analgesics during study treatment, or high tolerance to opioids precluding the ability to relieve treatment-associated discomfort with oxycodone or other analgesic, as judged by the investigator
• Active substance abuse or history of chronic substance abuse within 1 year prior to enrolment or prior chronic substance abuse (including alcoholism) likely to re-occur during the study period as judged by the investigator
• 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 visit
• Current use of any investigational agent (excluding antiretrovirals in Phase 3 evaluation to treat HIV infection)
• Unstable or poorly controlled hypertension or a recent history of a cardiovascular event which, in the opinion of the investigator, would put the patient at risk of adverse cardiovascular reactions related to the patch application procedure
• Evidence of another contributing cause for peripheral neuropathy, and/or treatment within 90 days prior to screening visit with any drug that may have contributed to the sensory neuropathy
• Past or current history of Type I or Type II diabetes mellitus
• Current psychotic disorders
• Clinically significant abnormal ECG at screening
• Hypersensitivity to capsaicin (i.e., chilli peppers or Over-the-counter [OTC] capsaicin products), any QUTENZA excipients, local anesthetics, oxycodone, hydrocodone, or adhesives
• Significant ongoing 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
• Significant pain of an aetiology other than painful HIV-AN, PHN, PNI, ISNN or other adequately characterized PNP for example, compression-related neuropathies (e.g., spinal stenosis), fibromyalgia or arthritis
• Posttraumatic neuropathic pain due to Complex Regional Pain Syndrome (CRPS, Type I)
• Active malignancy or history of malignancy during the past 5 years (a history of squamous cell carcinoma or a basal cell carcinoma not involving the area to be treated is allowed)
• Evidence of cognitive impairment including dementia that may interfere with subject's ability to complete study evaluations and recall pain levels in the past 24 hours
• Planned elective surgery during the trial
• Neuropathic pain areas located only on the face, above the hairline of the scalp, and/or in proximity to mucous membranes
• Female subjects of child-bearing potential with a positive serum or urine pregnancy test prior to treatment