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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
61
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 or 7.5 mg, twice a day approximately every 12 hours over an 8 day period.
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.
Radiant Research
Chandler, Arizona, United States
Premier Research Center
Peoria, Arizona, United States
Homestead Clinical Research
Cutler Bay (Miami), Florida, United States
San Marcus Research Clinic
Miami, Florida, United States
Boston Clinical Trials
Boston, Massachusetts, United States
Quest Research Institute
Bingham Farms, Michigan, United States
Affiliated Clinical Research
Las Vegas, Nevada, United States
Radiant Research
Las Vegas, Nevada, United States
Radiant Research
Dallas, Texas, United States
Sum of the Pain Intensity Difference at 6 hours (SPID-6)
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.
Time frame: Baseline to 6 hours after initial dose
12-Hour Pain Intensity Scores Assessed with a Numerical Pain Rating Scale (NPRS-12)
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.
Time frame: Seven Day Treatment Period
Summed Pain Intensity Difference (SPID) at Various Time Points
Pain intensity is measured with a numerical pain rating scale assessing "pain right now" where 0=no pain and 10=worst pain imaginable. Pain intensity difference (PID) is calculated by subtracting the pain intensity score at each time point from the Baseline pain intensity score. SPID (Sum of the Pain Intensity Difference) score will be calculated by summing weighted PID scores over the time period, where the weight assigned to each PID score is equal to the elapsed time since the previous scheduled time point. SPID will be assessed at 1,2,4,8,10 and 12 hours following first dose.
Time frame: 1 hour period, 2 hour period, 4 hour period, 8 hour period, 10 hour period, 12 hour period
Total Pain Relief (TOTPAR) at 6 hours
Pain relief will be assessed at 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 12 hours following study drug administration using a numerical pain relief scale (NPR), where 0 = no relief, 1=little relief, 2=some relief, 3=a lot of relief, and 4 = complete relief. Total Pain Relief (TOTPAR) is calculated by summing the hourly NPR scores using the area under the NPR curve. TOTPAR will be assessed from Baseline to 6 hours following dosing.
Time frame: Baseline to 6 hours after initial dose
Pain Intensity Difference (PID) at Various Time Points
Pain intensity scores (assessing pain right now) will be recorded using a numerical pain rating scale for pain right now (NPRS-NOW) at 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 12 hours following study drug administration. Pain will be rated on an 11-point numerical scale where 0 = no pain and 10 = worst pain imaginable.
Time frame: 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
Pain Relief (PAR) at Various Time Points
Pain relief compared with Baseline will be assessed at 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 12 hours following study drug administration 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.
Time frame: 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
At 6- hours following the first dose of study medication the subject will be asled to assess their overall impression of the study medication and rate it on a 5-point scale, where 0 = poor, 1 = fair, 2 = good, 3 = very good, 4 = excellent. Subjects will rate the study medication based on their perception of its efficacy and tolerability.
Time frame: 6 hours after initial dose (or immediately prior to receiving rescue medication)
Subject-rated Global Evaluation of Study Medication at the Follow-up Visit on Day 8
At the follow-up visit on Day 8, the subject will be asked to assess their overall impression of the study medication and rate it on a 5-point scale, where 0 = poor, 1 = fair, 2 = good, 3 = very good, 4 = excellent. Subjects will rate the study medication based on their perception of its efficacy and tolerability.
Time frame: Follow-up Visit
Total Pain Relief (TOTPAR) at 12 hours
Pain relief will be assessed at 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 12 hours following study drug administration using a numerical pain relief scale (NPR), where 0 = no relief, 1=little relief, 2=some relief, 3=a lot of relief, and 4 = complete relief. Total Pain Relief (TOTPAR) is calculated by summing the hourly NPR scores using the area under the NPR curve. TOTPAR will be assessed until 12 hours after dosing.
Time frame: Baseline to 12 hours
Time to First Rescue Medication Use
Time to the first rescue medication use will be calculated by determining the number of minutes between the time the first dose of study drug was taken and the time of the first request for rescue analgesia. For subjects who did not take any rescue medication, the time to the first rescue medication use will be censored at the time of the final pain assessment during the observation period. If the time to event is greater than 6 hours, subjects will be assigned a time of 6 hours and will be considered censored in the statistical analysis.
Time frame: Baseline to 6 hours after initial dose
Treatment Responders at 6 Hours
Subjects will be considered responders for the 6-hour observation period if they demonstrate at least 30% improvement in NPRS-NOW score, and a Pain Relief score \> 1, and a Global Evaluation Score of 2, 3, or 4.
Time frame: Baseline to 6 hours after initial dose
Neuropathic Pain Scale (NPS) Ratings at Various Time Points
The Neuropathic Pain Scale (NPS) is an instrument designed to measure 6 different pain qualities (sharp, dull, hot, cold, sensitive, and itchy), the overall intensity of the pain, its subjective unpleasantness and two ratings of special characteristics (deep and surface pain) to characterize most manifestations of neuropathic pain on an 11-point categorical scale. The maximum total score is 100, with higher scores indicating greater severity.
Time frame: Baseline (prior to initial dose), and at 1, 2, 4, and 6 hours and follow up visit
Tactile Allodynia Assessment at Various Time Points
Tactile Allodynia measures the patient's perception of innocuous stimuli as painful. A standard paintbrush (supplied by the Sponsor) will be brushed over a 5 cm area of skin at the site of maximum pain sensitivity and the subject will rate the severity of pain on a 100 mm VAS scale. The assessment will be performed on symmetrical dermatomes and compared.
Time frame: Baseline (prior to initial dose), and at 1, 2, 4, and 6 hours and follow up visit
Treatment Responders for the Treatment Period
Subjects will be considered responders for the 7-Day Treatment Period if they demonstrate a 30% improvement in NPRS-12 compared to the average NPRS-12 score from the three day period before the Treatment Visit, and if they report a Global Evaluation score of 2, 3, or 4.
Time frame: Baseline to Day 8
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