A Multicenter Randomized, Double-Blind, Controlled Study of NGX-4010 for the Treatment of Painful HIV-Associated Neuropathy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 494
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
NGX-4010, 60 minutes
干预措施: NGX-4010, 8% capsaicin patch (Drug)
NGX-4010, 30 minutes
干预措施: NGX-4010, 8% capsaicin patch (Drug)
0.04% conc. capsaicin patch, 60 min.
干预措施: 0.04% capsaicin patch (Drug)
0.04% conc. capsaicin patch, 30 min.
干预措施: 0.04% capsaicin patch (Drug)
结局指标
主要结局
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.
时间窗: 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.
次要结局
- 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)