A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose, Multicenter, Parallel Group Study to Evaluate the Safety and Analgesic Activity of ATx08-001 When Administered to Subjects With Postherpetic Neuralgia
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Postherpetic Neuralgia
- Sponsor
- Aestus Therapeutics
- Enrollment
- 61
- Locations
- 7
- Primary Endpoint
- Sum of the Pain Intensity Difference at 6 hours (SPID-6)
- Status
- Completed
- Last Updated
- 14 years ago
Overview
Brief Summary
This is a Phase 2 randomized, double-blind, placebo-controlled, multiple-dose, multicenter, parallel-group study to evaluate the analgesic activity of ATx08-001, a novel selective peroxisome proliferator-activated receptor modulator (SPPARM), in subjects with moderate-to-severe postherpetic neuralgia pain. Eligible subjects will be randomized to receive either placebo or Atx08-001. Study drug will be administered orally twice a day for 7 days. Subjects will be evaluated for neuropathic pain intensity at regular intervals over a 6 hour period on Day 1 following the first dose of study drug. They will then be discharged from the clinic and will complete diary assessments of pain severity twice a day at home. Subjects will be asked to return to the clinic on Day 8 to complete their last set of pain evaluations.
Detailed Description
Aestus has identified a novel selective peroxisome proliferator-activated receptor modulator (SPPARM), with promising potential for the treatment of neuropathic pain. PPARs are nuclear receptors that control many cellular and metabolic processes and are readily modulated by a variety of different drugs. Drugs modulating this target have been shown to improve blood glucose levels and levels of blood lipids, and may reduce the risk of atherosclerosis. The primary objective of the study is to evaluate the safety and analgesic efficacy of ATx08-001 at doses of 2.5 mg bid and 7.5 mg bid compared to placebo for the control of moderate-to-severe postherpetic neuralgia (PHN) pain. The secondary objectives are: * To determine the approximate time to onset of analgesia following administration of study drug * To determine the approximate duration of analgesia following study drug administration * To determine the percentage of treatment responders among subjects receiving ATx08-001 Subjects will be given a diary and instructed to record their postherpetic neuralgia pain severity on a Numerical Pain Rating Scale (NPRS - 12) "over the past 12 hours" on a 0 - 10 scale with "0" being no pain and "10" being the most severe pain the subject could imagine, each morning and night for three consecutive days prior to returning for the Treatment Visit. The Treatment Visit will consist of an in-clinic 6-hour observation period. To be eligible for dosing, immediately before dosing subjects must report a baseline score of 4 or greater on the following Numerical Pain Rating Scale (NPRS-NOW) question: "How would you rate your pain RIGHT NOW using a zero to ten scale, where zero equals no pain and ten is the worst pain you can imagine." Qualified subjects will be administered study drug followed by a 6-hour observation in-clinic period. In addition to the Baseline pain intensity assessment conducted just prior to drug administration (Time 0), pain intensity scores (pain right now) will be assessed using the NPRS-NOW at 30 minutes, 1, 2, 3, 4, and 6 hours following study drug administration. Pain relief compared with Baseline will be assessed at those same time points using a 5-point numerical pain relief (NPR) scale, where 0 = no relief, 1 = a little relief, 2 = some relief, 3 = a lot of relief, and 4 = complete relief. Subjects will be discharged from the clinic at the end of the 6-hour observation period and will be instructed to record postherpetic neuralgia pain severity (NPRS-NOW scores) and pain relief (PAR scores) at 8, 10 and 12 hours following dosing in a diary.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Is able to provide written informed consent prior to study entry
- •Is male or female, 18 - 85 years of age
- •Has a diagnosis of postherpetic neuralgia that has been present for at least 3 months since the resolution of the skin rash (shingles), and has been associated with at least moderate pain
- •Has a body mass index (BMI) between 17 and 36, inclusive
- •Has on average postherpetic neuralgia pain severity of at least "4" on the 11-point NPRS-12 scale over three days prior to the Treatment Visit.
- •At the Treatment Visit, entry into the study for dosing will require a baseline score of 4 or greater on the following 'Numerical Pain Rating Scale' (NPRS-NOW): "How would you rate your pain RIGHT NOW using a zero to ten scale, where zero equals no pain and ten is the worst pain you can imagine." If the subject fails to qualify for the Treatment Visit because of a baseline pain score below 4, he or she may return on any day within a fourteen day period to attempt to qualify again. A subject will be allowed a maximum of two reassessments to qualify on the basis of the NPRS-NOW scale.
- •Female subjects must be of non childbearing potential (defined as postmenopausal for at least 1 year or surgically sterile \[bilateral tubal ligation, bilateral oophorectomy or hysterectomy\]) or must be using adequate contraception (practicing one of the following methods of birth control):
- •Total abstinence from sexual intercourse (minimum of one complete menstrual cycle before study entry),
- •A partner who is physically unable to impregnate the subject (e.g., vasectomized)
- •Contraceptives (oral, parenteral, or transdermal) for 3 consecutive months prior to study drug administration,
Exclusion Criteria
- •Has another source of moderate-to-severe pain apart from the postherpetic neuralgia that might be confused with the PHN pain
- •Is actively abusing alcohol or drugs
- •Is unable to refrain from alcohol for a period beginning 24 hours prior to the treatment visit until the end of the study
- •Is scheduled to undergo any surgical procedures during the period of study duration
- •Has a history of any active serious medical conditions including cancer (with the exception of benign uterine dysplasia or removed skin carcinomas), cardiovascular, respiratory, renal, hepatic, gastrointestinal, endocrine, immunologic, hematologic, neurologic or psychiatric disease that would contraindicate study participation
- •Has moderate to severe (New York Heart Association \[NYHA\] Class 3 or 4) heart failure defined as heart failure which significantly limits physical activity by provoking fatigue, palpitations or dyspnea.
- •Has a history of either type 1 or type 2 diabetes mellitus
- •Has taken a fixed scheduled opioid regimen within 3 days prior to the Treatment Visit. A fixed scheduled regimen of another type of analgesic, e.g., nonsteroidal antiinflammatory drug (NSAID) or an adjuvant analgesic will be allowed as long as the dose and schedule of administration were not changed for at least 2 weeks prior to dosing.
- •Has used a short-acting "as needed" opioid less than 12 hours prior to dosing or an "as needed" NSAID dose less than 24 hours prior to dosing
- •Has used extended duration oral analgesics up to 48 hours prior to the Treatment Visit
Arms & Interventions
Placebo
Placebo will be administered as a 6mm white film coated tablet, twice a day approximately every 12 hours over an 8 day period. Placebo is identical in appearance to the ATx 08-001 tablet.
Intervention: Placebo
ATx08-001 2.5 mg bid
ATx08-001 will be administered as a 6mm white film coated tablet of 2.5 mg strength, to be taken orally at a dose of 2.5 mg, twice a day approximately every 12 hours over an 8 day period.
Intervention: ATx08-001
ATx08-001 7.5 mg bid
ATx08-001 will be administered as a 6mm white film coated tablet of 2.5 mg strength, to be taken orally at a dose of 7.5 mg, twice a day approximately every 12 hours over an 8 day period.
Intervention: ATx08-001
Outcomes
Primary Outcomes
Sum of the Pain Intensity Difference at 6 hours (SPID-6)
Time Frame: Baseline to 6 hours after initial dose
Pain intensity will be measured with a numerical pain rating scale assessing "pain right now" where 0=no pain and 10=worst pain you can imagine. Pain intensity difference (PID) will be calculated by subtracting the pain intensity score at each time point from the Baseline pain intensity score. The SPID (Sum of the Pain Intensity Difference) score will be calculated by summing weighted PID scores over 6 hours, where the weight assigned to each PID score is equal to the elapsed time (in hours) since the previous scheduled evaluation time point.
12-Hour Pain Intensity Scores Assessed with a Numerical Pain Rating Scale (NPRS-12)
Time Frame: Seven Day Treatment Period
Pain intensity over the 7 day treatment period will be assessed using a numerical pain rating scale that assesses the subject's perception of average pain intensity over the past 12 hours (NPRS-12). The NPRS-12 will be completed by the subject every morning and evening for seven days. Pain intensity will be measured using an 11-point numerical scale where 0 = no pain and 10 = worst pain imaginable.
Secondary Outcomes
- Total Pain Relief (TOTPAR) at 6 hours(Baseline to 6 hours after initial dose)
- Pain Relief (PAR) at Various Time Points(Baseline (prior to first dose), 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours and 12 hours after initial dose)
- Subject-rated Global Evaluation of Study Medication at the Follow-up Visit on Day 8(Follow-up Visit)
- Time to First Rescue Medication Use(Baseline to 6 hours after initial dose)
- Treatment Responders at 6 Hours(Baseline to 6 hours after initial dose)
- Neuropathic Pain Scale (NPS) Ratings at Various Time Points(Baseline (prior to initial dose), and at 1, 2, 4, and 6 hours and follow up visit)
- Tactile Allodynia Assessment at Various Time Points(Baseline (prior to initial dose), and at 1, 2, 4, and 6 hours and follow up visit)
- Summed Pain Intensity Difference (SPID) at Various Time Points(1 hour period, 2 hour period, 4 hour period, 8 hour period, 10 hour period, 12 hour period)
- Total Pain Relief (TOTPAR) at 12 hours(Baseline to 12 hours)
- Pain Intensity Difference (PID) at Various Time Points(Baseline (prior to first dose), 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours and 12 hours after initial dose)
- Subject-rated Global Evaluation of Study Medication at 6 hours(6 hours after initial dose (or immediately prior to receiving rescue medication))
- Treatment Responders for the Treatment Period(Baseline to Day 8)