Clinical trial NCT00064623: Study of NGX-4010 for the Treatment of Painful HIV-Associated Neuropathy
Official title: A Randomized, Double-Blind, Controlled Dose Finding Study of NGX-4010 for the Treatment of Painful HIV-Associated Distal Symmetrical Polyneuropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Peripheral Nervous System Diseases
Pain
Keywords: Dermal assessment
Pain measurement
Diary
Analgesics/*therapeutic use
Capsaicin/*administration & dosage/adverse effects
HIV Infections/*complications/*drug therapy
Peripheral Nervous System Diseases/*complications/diagnosis/*therapy
Peripheral Nervous System Diseases/drug therapy/*etiology/physiopathology
Lead sponsor: NeurogesX
Sponsor class: INDUSTRY
First posted: 2003-07-11
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to determine if an investigational drug, NGX-4010 (high-concentration capsaicin patch), is effective in treating painful HIV-associated neuropathy.

Detailed description: The C107 study is a randomized, double-blind, controlled dose finding study of NGX-4010 for the treatment of painful symptoms of HIV-associated neuropathy. Participants will be randomly assigned to receive initial treatment according to one of three doses (application durations), and to receive double-blind NGX-4010 patch (high-concentration capsaicin) or matching control (low-concentration capsaicin).

Participants who complete study evaluations through Week 12 will have the option of receiving up to 3 additional open-label treatments.

Eligibility criteria: Inclusion Criteria:

* At least 18 years of age
* Documented evidence of HIV-1 infection
* Documented diagnosis of painful HIV-associated distal symmetrical polyneuropathy established by a neurologist resulting from HIV disease and/or antiretroviral drug exposure, with primary 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, and at least one of the following: distal diminution of vibration sensation or pain or temperature sensation in the legs
* Either no neurotoxic antiretroviral (didanosine, zalcitabine or stavudine) exposure for at least 8 weeks prior to Screening Visit, or currently on stable dose(s) of any neurotoxic antiretroviral(s) for at least 8 weeks prior to Screening Visit
* Screening Pain Sum Score of 12 to 36
* Karnofsky Performance Score of greater than or equal to 60
* Intact, unbroken skin over the painful area(s) to be treated
* If taking chronic pain medications, be on a stable (not PRN) regimen for at least 21 days prior to Treatment Visit and willing to maintain these medications at the same stable dose(s) and schedule throughout the 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 participating in a conception process during study and for 30 days following experimental drug exposure
* Willing and able to comply with protocol requirements for duration of study

Exclusion Criteria:

* Concomitant opioid medication, unless orally or transdermally administered and not exceeding a total daily dose of morphine 60 mg/day, or equivalent. Parenteral opioid use is excluded, regardless of dose
* Unavailability of an effective rescue medication strategy for the subject, such as unwillingness to use opioid analgesics during treatment, or high tolerance to opioids precluding the ability to relieve treatment-associated discomfort with Roxicodone® or Vicodin®, as judged by the Investigator
* Active substance abuse or history of chronic substance abuse within the past year, or prior chronic substance abuse judged likely to recur during the study period by the investigator
* Recent use (within 21 days preceding the Treatment Visit of any topically applied pain medication, such as non-steroidal anti-inflammatory drugs, menthol, methyl salicylate, local anesthetics (including Lidoderm®), steroids or capsaicin products on the painful areas
* Current use of any investigational agent or Class 1 anti-arrhythmic drugs
* Significant pain of an etiology other than painful HIV-associated neuropathy; significant ongoing pain from other cause(s) that may interfere with judging HIV-associated neuropathy pain
* Evidence of another contributing cause for peripheral neuropathy, e.g., diabetes mellitus requiring medication control (i.e., oral hypoglycemics, insulin); hereditary neuropathy; vitamin B12 deficiency (B12 level ≤ 200 pg/mL) or less than 3 months of B12 supplementation prior to Screening Visit; or treatment within 90 days prior to Screening Visit with any drug that may have contributed to the sensory neuropathy
* Any implanted medical device (spinal cord stimulator, intrathecal pump or peripheral nerve stimulator) for the treatment of neuropathic pain
* Treatment for acute opportunistic infections within 14 days before Treatment Visit
* Presence of acute, active opportunistic infection, except oral thrush; oral, genital, or rectal herpes; and Mycobacterium avium bacteremia within 2 weeks prior to Screening Visit
* Currently have active malignant disease
* 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
* Hypersensitivity to capsaicin (i.e., chili peppers or OTC capsaicin products), local anesthetics, Roxicodone®, Vicodin®, or adhesives

Primary outcomes:
measure: Percent change from baseline in the "average pain for the past 24 hours" Numeric Pain Rating Scale (NPRS) score (i.e., average of scores during Weeks 2-12, compared to baseline)
Secondary outcomes:
measure: Percent change from baseline in the "average pain for the past 24 hours" NPRS score (i.e., average of scores during Weeks 2-4 and 2-8, respectively, compared to baseline)
measure: Proportion of subjects reaching 30% decrease from baseline in their "average pain for the past 24 hours" NPRS scores on average during Weeks 2-12, within each treatment group
measure: Proportion of subjects reaching 30% decrease from baseline in their "average pain for the past 24 hours" NPRS scores on average during Weeks 2-4 and 2 8, respectively, within each treatment group
measure: Percent change from baseline in the "worst pain for the past 24 hours" and "pain now" NPRS scores (baseline score compared to the average of scores from Weeks 2 -12), within each treatment group
measure: "Pain now" on evening of treatment day
measure: Mean onset and duration of efficacy in days within each treatment group
measure: Proportion of subjects with significant changes in concomitant pain medication usage during Weeks 2-12, compared to baseline
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: NeurogesX Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: NeurogesX Investigational Site
state: Arizona
city: Berkeley
country: United States
facility: NeurogesX Investigational Site
state: California
city: San Diego
country: United States
facility: NeurogesX Investigational Site
state: California
city: San Francisco
country: United States
facility: NeurogesX Investigational Site
state: California
city: Stanford
country: United States
facility: NeurogesX Investigational Site
state: California
city: West Hollywood
country: United States
facility: NeurogesX Investigational Site
state: California
city: Fort Lauderdale
country: United States
facility: NeurogesX Investigational Site
state: Florida
city: Miami
country: United States
facility: NeurogesX Investigational Site
state: Florida
city: Miami
country: United States
facility: NeurogesX Investigational Site
state: Florida
city: North Palm Beach
country: United States
facility: NeurogesX Investigational Site
state: Florida
city: Orlando
country: United States
facility: NeurogesX Investigational Site
state: Florida
city: Sunrise
country: United States
facility: NeurogesX Investigational Site
state: Florida
city: Vero Beach
country: United States
facility: NeurogesX Investigational Site
state: Florida
city: Honolulu
country: United States
facility: NeurogesX Investigational Site
state: Hawaii
city: Chicago
country: United States
facility: NeurogesX Investigational Site
state: Illinois
city: Lexington
country: United States
facility: NeurogesX Investigational Site
state: Kentucky
city: Baltimore
country: United States
facility: NeurogesX Investigational Site
state: Maryland
city: Boston
country: United States
facility: NeurogesX Investigational Site
state: Massachusetts
city: Springfield
country: United States
facility: NeurogesX Investigational Site
state: Massachusetts
city: Detroit
country: United States
facility: NeurogesX Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: NeurogesX Investigational Site
state: Minnesota
city: St. Louis
country: United States
facility: NeurogesX Investigational Site
state: Missouri
city: Camden
country: United States
facility: NeurogesX Investigational Site
state: New Jersey
city: Albany
country: United States
facility: NeurogesX Investigational Site
state: New York
city: New York
country: United States
facility: NeurogesX Investigational Site
state: New York
city: New York
country: United States
facility: NeurogesX Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: NeurogesX Investigational Site
state: North Carolina
city: Cleveland
country: United States
facility: NeurogesX Investigational Site
state: Ohio
city: Portland
country: United States
facility: NeurogesX Investigational Site
state: Oregon
city: Austin
country: United States
facility: NeurogesX Investigational Site
state: Texas
city: Dallas
country: United States
facility: NeurogesX Investigational Site
state: Texas
city: Houston
country: United States
facility: NeurogesX Investigational Site
state: Texas
city: San Antonio
country: United States
facility: NeurogesX Investigational Site
state: Texas
city: Madison
country: United States
facility: NeurogesX Investigational Site
state: Wisconsin
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: David M Simpson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NeurogesX
name: Jeffrey Tobias, MD
role: STUDY_DIRECTOR
References:
citation: Simpson DM, Brown S, Tobias JK, Vanhove GF; NGX-4010 C107 Study Group. NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: results of a 52-week open-label study. Clin J Pain. 2014 Feb;30(2):134-42. doi: 10.1097/AJP.0b013e318287a32f.
citation: Brown S, Simpson DM, Moyle G, Brew BJ, Schifitto G, Larbalestier N, Orkin C, Fisher M, Vanhove GF, Tobias JK. NGX-4010, a capsaicin 8% patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: integrated analysis of two phase III, randomized, controlled trials. AIDS Res Ther. 2013 Jan 28;10(1):5. doi: 10.1186/1742-6405-10-5.
citation: Simpson DM, Brown S, Tobias J; NGX-4010 C107 Study Group. Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy. Neurology. 2008 Jun 10;70(24):2305-13. doi: 10.1212/01.wnl.0000314647.35825.9c.