The Efficacy of MK-8291 in Participants With Post-herpetic Neuralgia (PHN) With Allodynia (MK-8291-012)

A Randomized Clinical Trial to Study the Efficacy, Safety, and Tolerability of MK-8291 in Subjects With Post-Herpetic Neuralgia With Allodynia

This study aims to determine whether MK-8291 is effective in reducing pain in participants with post-herpetic neuralgia (PHN) with allodynia.

The primary hypothesis is that when compared to placebo, treatment with MK-8291 reduces the change from Baseline in participant-reported pain intensity by 1 on an 11-point numeric rating scale.

Study Overview

• Status: Completed
• Conditions: Postherpetic Neuralgia
• Intervention / Treatment: Drug: Placebo; Drug: MK-8291

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• non-pregnant female (and/or partner) agrees to use two acceptable methods of birth control throughout the trial until 2 weeks after the last dose of treatment
• female is postmenopausal or surgically sterile
• has a clinical diagnosis of PHN with allodynia for at least 3 months duration after healing of rash
• has a body mass index (BMI) =< 35 kg/m^2, inclusive
• is in good health, with exception of PHN
• is on a stable dose for at least 30 days prior to screening if taking any of the following: opioids, non-opioids, paracetomol, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, antidepressants
• is a nonsmoker or has not used nicotine or nicotine containing products for at least prior 3 months

Exclusion Criteria:

• has a non-PHN chronic pain state
• has a history of clinically significant and inadequately treated endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases
• has a history of malignant cancer
• has a history or presence of esophagitis
• has a history of significant multiple and/or severe allergies (e.g. food, drug, latex), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
• is positive for hepatitis B surface antigen, hepatitis C antibodies, or human immunodeficiency virus (HIV)
• had major surgery, donated or lost approximately 500 mL of blood within 4 weeks prior to screening
• has participated in another investigational trial within 4 weeks prior to screening
• has a history of risk factors for Torsades de Pointes, has hypokalemia or hypomagnesemia
• has a history or presence of clinically significant cardiac arrhythmia, taking substances with the target of reducing heart rate and or exercising endurance sports
• has had an injection of local anesthetics or steroids in the region affected by PHN, within 35 days prior to randomization
• anticipates using prescription and non-prescription drugs or herbal remedies during trial
• consumes excessive amounts of alcoholic or caffeinated beverages
• uses cannabis, any illicit drugs, or has a history of drug (including alcohol) abuse within 12 months of screening visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MK-8291 → Placebo; In Treatment Period 1, participants were orally administered 10 mg MK-8291 once daily on Days 1 and 2, twice daily on Days 3 to 27, and once daily on Day 28 of the period. After Treatment Period 1, participants were to undergo a minimum of a 7-day Washout Period, which was followed by Treatment Period 2. In Treatment Period 2, participants were orally administered Placebo once daily on Days 1 and 2, twice daily on Days 3 to 27, and once daily on Day 28 of the period. (Total duration of treatment: up to approximately 63 days)	Drug: Placebo; Placebo oral tablets; Drug: MK-8291; MK-8291 oral tablets
EXPERIMENTAL: Placebo → MK-8291; In Treatment Period 1, participants were orally administered Placebo once daily on Days 1 and 2, twice daily on Days 3 to 27, and once daily on Day 28 of the period. After Treatment Period 1, participants were to undergo a minimum of a 7-day Washout Period, which was followed by Treatment Period 2. In Treatment Period 2, participants were orally administered 10 mg MK-8291 once daily on Days 1 and 2, twice daily on Days 3 to 27, and once daily on Day 28 of the period. (Total duration of treatment: up to approximately 63 days)	Drug: Placebo; Placebo oral tablets; Drug: MK-8291; MK-8291 oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Pain Intensity at Week 4 of Each Treatment Period	Participants completed a pain intensity questionnaire, the Numerical Rating Scale (NRS), in the morning prior to taking study treatment at Baseline (Day 1) in each treatment period, and then daily up to Day 28 in each treatment period. The NRS assesses the intensity of Post-herpetic Neuralgia (PHN) pain during the preceding 24-hour period on an 11-point numeric rating scale (range: 0=no pain to 10=pain as bad as you can imagine). The mean score in pain intensity of Week 4 (Days 22 to 28) minus the mean score at Baseline is presented, with a negative change representing improvement (or reduction) in pain intensity. In comparison to placebo, a reduction (difference in the change from Baseline) of 1 on the 11-point NRS is expected.	Baseline and Days 22-28 of each treatment period (Up to approximately 63 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving a 30 Percent or Greater Change From Baseline to Day 28 in Pain Intensity	Participants completed a pain intensity questionnaire, the Numerical Rating Scale (NRS) in the morning before taking study treatment at Baseline (Day 1) in each treatment period, and then daily from Day 1 up to Day 28 in each treatment period. The NRS assesses the intensity of PHN pain during the preceding 24-hour period on an 11-point numeric rating scale (range: 0=no pain to 10=pain as bad as you can imagine). This was a binary outcome denoting whether the participant reported a percent change from Baseline to Week 4 (Days 22 to 28) in the mean pain intensity score greater than 30%. The percentage of participants who reported a 30% or greater change from Baseline to Day 28 of each treatment period is presented.	Baseline and Day 28 in each treatment period (Up to approximately 63 days)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 12, 2015
• Primary Completion (ACTUAL): February 29, 2016
• Study Completion (ACTUAL): February 29, 2016

Study Registration Dates

• First Submitted: January 5, 2015
• First Submitted That Met QC Criteria: January 12, 2015
• First Posted (ESTIMATE): January 13, 2015

Study Record Updates

• Last Update Posted (ACTUAL): December 9, 2019
• Last Update Submitted That Met QC Criteria: November 20, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Sensation Disorders; Somatosensory Disorders; Neuralgia; Hyperalgesia; Neuralgia, Postherpetic
• Other Study ID Numbers: 8291-012; 2014-002396-28 (EUDRACT_NUMBER); MK-8291-012 (OTHER: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf