Study to Evaluate the Safety and Analgesic Activity of ATx08-001 in Subjects With Postherpetic Neuralgia

NCT01318226 | Completed Phase 2

• 2 other identifiers: ATX-1001R44NS059140
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 9

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.

Conditions

Postherpetic Neuralgia

Keywords

postherpetic neuralgia; shingles; analgesia; neuropathic pain

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Seven Day Treatment Period

Secondary Outcomes (12)

• 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 6 hours

  Baseline to 6 hours after initial dose

• 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

• 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 6 hours

  6 hours after initial dose (or immediately prior to receiving rescue medication)

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

ATx08-001 2.5 mg bid

EXPERIMENTAL

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.

Drug: ATx08-001

ATx08-001 7.5 mg bid

EXPERIMENTAL

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.

Drug: ATx08-001

Interventions

ATx08-001 DRUG

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.

ATx08-001 2.5 mg bid; ATx08-001 7.5 mg bid

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,
• Intrauterine device (IUD), or
• Double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream)
• If female of childbearing potential, subject must have a negative serum pregnancy test at screening
• Able to communicate meaningfully with the study observer and staff
• No known allergies to study medication

You may not qualify if:

• 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
• Has applied lidocaine patches or dermal analgesics within 7 days prior to the Treatment Visit
• Has received an anesthetic block within two weeks of the Screening Visit
• Has received any prior neurolytic nerve block in the area of the PHN pain
• Is taking tricyclic, selective serotonin reuptake inhibitor (SSRI) or serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressants for PHN (or for indications other than pain) and the dosage has been changed within 14 days of the Treatment Visit. Only subjects on stable doses from at least 14 days prior to the Treatment Visit through the duration of the study will be eligible to participate
• Is taking gabapentin (Neurontin), pregabalin (Lyrica), or duloxetine (Cymbalta) and the dosage has been changed within 14 days of the Treatment Visit. Only subjects receiving stable doses for at least 14 days prior to the Treatment Visit and are willing to continue taking the same doses for the duration of the study will be eligible to participate

Sponsors & Collaborators

• Aestus Therapeutics: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Symbiance, Inc: collaborator
• Parallax Clinical Research, LLC: collaborator

Study Sites (9)

Radiant Research

Chandler, Arizona, 85225, United States

Location

Premier Research Center

Peoria, Arizona, 85381, United States

Location

Homestead Clinical Research

Cutler Bay (Miami), Florida, 33189, United States

Location

San Marcus Research Clinic

Miami, Florida, 33015, United States

Location

Boston Clinical Trials

Boston, Massachusetts, 02135, United States

Location

Quest Research Institute

Bingham Farms, Michigan, 48025, United States

Location

Affiliated Clinical Research

Las Vegas, Nevada, 89106, United States

Location

Radiant Research

Las Vegas, Nevada, 89146, United States

Location

Radiant Research

Dallas, Texas, 75231, United States

Location

MeSH Terms

Conditions

Neuralgia, Postherpetic; Herpes Zoster; Agnosia; Neuralgia

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Perceptual Disorders; Neurobehavioral Manifestations

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2011
• First Posted: March 18, 2011
• Study Start: March 1, 2011
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: August 23, 2011

Record last verified: 2011-08

Locations

US (9)