Study of NGX-4010 for the Treatment of Painful HIV-Associated Neuropathy

Phase 3

Completed

Conditions: Peripheral Nervous System Diseases
HIV Infections
Pain

Interventions: Drug: NGX-4010, 8% capsaicin patch
Drug: 0.04% capsaicin patch

Registration Number: NCT00321672

Lead Sponsor: NeurogesX

Brief Summary: The purpose of the study was to assess the efficacy and safety of NGX-4010 applied for 30 or 60 minutes for the treatment of painful HIV-associated neuropathy.

Detailed Description: Study C119 was a multicenter, randomized, double-blind, controlled evaluation of the efficacy and safety of NGX-4010 for the treatment of painful HIV-associated neuropathy. Eligible subjects had painful HIV-associated neuropathy resulting from HIV disease and/or antiretroviral drug exposure in both feet, with average numeric pain rating scale (NPRS) scores during screening of 3 to 9 (inclusive). Up to four patches covering an area of up to 1120 square centimeters could be used during a single treatment administration in this study. Subjects were randomly assigned to receive active NGX-4010 patches (8% capsaicin) or low-concentration control patches (0.04% capsaicin) identical in appearance, at doses (patch application duration) of either 30 or 60 minutes, according to a 2:1:2:1 allocation scheme.

Subjects could be on stable chronic oral pain medication regimens, but could not be using any topical pain medications on the affected areas. NPRS scores for the average pain in the past 24 hours were recorded daily in the evening, beginning on the day of the Screening Visit (usually on Day -14). Subjects continued to record NPRS scores in a take-home diary from the evening on the day of treatment through the evening before the Termination Visit at Week 12. Subjects returned for interim follow-up visits at Weeks 4 and 8 following study treatment.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 494

Inclusion Criteria

Documented evidence of HIV-1 infection
Documented diagnosis of painful HIV-associated distal symmetric polyneuropathy resulting from HIV disease and/or antiretroviral drug exposure To be confirmed based on symptoms of pain, burning or dysesthetic discomfort in both feet for at least 2 months prior to Screening Visit, AND absent or diminished ankle reflexes OR at least one of following: distal diminution of vibration sensation or pain or temperature sensation in legs
Average NPRS scores during screening period of 3 to 9, inclusive
Life expectancy of 12 months or longer per Investigator's judgment
Intact, unbroken skin over painful areas to be treated
If taking chronic pain medications, be on stable regimen for at least 21 days prior to Day 0 and willing to maintain medications at same stable dose(s) and schedule throughout study
Female subjects with child-bearing potential: negative serum pregnancy test performed at Screening Visit
Willing to use effective methods of birth control and/or refrain from conception process during study and for 30 days following study drug exposure
Willing and able to comply with protocol for duration of study

Exclusion Criteria

Concomitant opioid medication, unless orally or transdermally administered and not exceeding total daily dose of morphine 80 mg/day or equivalent; parenteral opioids not allowed
Unavailability of effective rescue medication strategy for subject, such as unwillingness to use opioid analgesics during study treatment or high tolerance to opioids precluding ability to relieve treatment-associated discomfort as judged by investigator
Active substance abuse or history of chronic substance abuse within past year or prior chronic substance abuse (including alcoholism) judged likely to recur during study period by investigator
Recent use (within 21 days preceding Day 0) of any topically applied pain medication, such as non-steroidal anti-inflammatory drugs, menthol, methyl salicylate, local anesthetics including Lidoderm® (lidocaine patch 5%), steroids or capsaicin products on painful areas
Started or stopped treatment with one or more neurotoxic antiretroviral agents (ie, didanosine [ddI], zalcitabine [ddC], or stavudine [d4T] during 8 weeks prior to Day 0
Participation in previous clinical trial in which subject received either blinded or open-label NGX-4010
Current use of any investigational agent or Class 1 anti-arrhythmic drugs (such as tocainide and mexiletine)
Evidence of another contributing cause for peripheral neuropathy, e.g., current uncontrolled diabetes mellitus (HbA1c≥9%) or history of diabetes mellitus preceding onset of HIV-associated neuropathy (HIV-AN); hereditary neuropathy; vitamin B12 deficiency (B12 level ≤200pg/mL at screening); or treatment within 90 days prior to Screening Visit with any drug that may have contributed to sensory neuropathy
Hypertension, unless adequately controlled by medication
Significant ongoing pain from other cause(s) that may interfere with judging HIV-AN related pain
Any implanted medical device for treatment of neuropathic pain
Hypersensitivity to capsaicin (i.e., chili peppers or over-the-counter (OTC) capsaicin products), local anesthetics, opioid-based oral analgesics or adhesives
Significant medical conditions (including active malignancy defined as treatment required in last 5 years) that in opinion of investigator would interfere with ability to complete study or evaluation of AEs
Recent significant medical-surgical intervention that in judgment of Investigator would interfere with ability to complete study or evaluation of AEs; examples include to major surgery, or receipt of immunosuppressive therapy within 3 months prior to Day 0
Evidence of cognitive impairment including dementia that may interfere with subject's ability to complete daily pain diaries requiring recall of average HIV-associated neuropathy pain level in past 24 hours

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NGX-4010, 60 minutes	NGX-4010, 8% capsaicin patch	-
NGX-4010, 30 minutes	NGX-4010, 8% capsaicin patch	-
0.04% conc. capsaicin patch, 30 min.	0.04% capsaicin patch	-
0.04% conc. capsaicin patch, 60 min.	0.04% capsaicin patch	-

Primary Outcome Measures

Name	Time	Method
The Primary Measure of Efficacy Was the Percent Change in the "Average Pain for the Past 24 Hours" Numeric Pain Rating Scale (NPRS) Score From Baseline During Weeks 2 to 12.	Weeks 2-12	Efficacy was assessed by daily Numeric Pain Rating Scale (NPRS) capturing "average pain for the past 24 hours" for painful HIV-associated neuropathy area(s) at approximately 9 PM every evening throughout the 12-week study period. The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain.

Secondary Outcome Measures

Name	Time	Method
Absolute Change in the Mean "Average Pain for the Past 24 Hours" Numeric Pain Rating Scale (NPRS) Score From Baseline During Weeks 2 to 12.	Weeks 2-12.
Proportion of Subjects Reaching 30% Decrease in Their Mean "Average Pain for the Past 24 Hours" Numeric Pain Rating Scale (NPRS) Score From Baseline During Weeks 2 to 12	Weeks 2-12