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

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02336555
• Collaborator: (none)
• Enrollment: 35
• Arms: 2
• Actual Duration (Months): 11.6

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Postherpetic Neuralgia	Drug: MK-8291; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized Clinical Trial to Study the Efficacy, Safety, and Tolerability of MK-8291 in Subjects With Post-Herpetic Neuralgia With Allodynia
• Actual Study Start Date: Mar 12, 2015
• Actual Primary Completion Date: Feb 29, 2016
• Actual Study Completion Date: Feb 29, 2016

Arms and Interventions

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: MK-8291; MK-8291 oral tablets; Drug: Placebo; Placebo 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: MK-8291; MK-8291 oral tablets; Drug: Placebo; Placebo oral tablets

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Pain Intensity at Week 4 of Each Treatment Period [Baseline and Days 22-28 of each treatment period (Up to approximately 63 days)]

   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.

Secondary Outcome Measures

1. Percentage of Participants Achieving a 30 Percent or Greater Change From Baseline to Day 28 in Pain Intensity [Baseline and Day 28 in each treatment period (Up to approximately 63 days)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT02336555
• Other Study ID Numbers: 8291-012; 2014-002396-28; MK-8291-012
• First Posted: Jan 13, 2015
• Last Update Posted: Dec 9, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Neuralgia; Neuralgia, Postherpetic; Hyperalgesia

Study Results

Participant Flow

Recruitment Details	Males and females with post-herpetic neuralgia (PHN) with allodynia, at least 18 years of age (inclusive) were enrolled in this study.

Arm/Group Title	MK-8291 → Placebo	Placebo → MK-8291
Arm/Group Description	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)	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)
Period Title: Treatment Period 1 (28 Days)
STARTED	18	17
COMPLETED	16	16
NOT COMPLETED	2	1
Period Title: Treatment Period 1 (28 Days)
STARTED	16	16
COMPLETED	16	15
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	MK-8291 → Placebo	Placebo → MK-8291	Total
Arm/Group Description	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)	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)	Total of all reporting groups
Overall Participants	18	17	35
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.7 (16.7)	54.7 (13.5)	55.7 (15.0)
Sex: Female, Male (Count of Participants)
Female	11 61.1%	14 82.4%	25 71.4%
Male	7 38.9%	3 17.6%	10 28.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	18 100%	17 100%	35 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	18 100%	17 100%	35 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Numerical Rating Scale (NRS) Pain Intesity Score at Baseline (Score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Score on a scale]	6.63 (1.02)	6.00 (0.97)	6.31 (1.03)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Pain Intensity at Week 4 of Each Treatment Period
Description	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.
Time Frame	Baseline and Days 22-28 of each treatment period (Up to approximately 63 days)

Outcome Measure Data

Analysis Population Description

The population consisted of participants who complied with the protocol sufficiently to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

Arm/Group Title	MK-8291	Placebo
Arm/Group Description	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 a treatment period. (Up to 28 days in each treatment period)	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 a treatment period. (Up to 28 days in each treatment period)
Measure Participants	30	32
Mean (95% Confidence Interval) [Score on a scale]	-1.776	-1.263

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-8291, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.075
	Comments	Linear mixed model with a posterior probability evaluation for the treatment effect
	Method	Linear mixed model
	Comments	One-sided p-value and a posterior probability greater than 90% that the treatment effect is less than 0.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.452
	Confidence Interval	(2-Sided) 95%; -1.076 to 0.172
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants Achieving a 30 Percent or Greater Change From Baseline to Day 28 in Pain Intensity
Description	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.
Time Frame	Baseline and Day 28 in each treatment period (Up to approximately 63 days)

Outcome Measure Data

Analysis Population Description

The population consisted of participants who complied with the protocol sufficiently to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

Arm/Group Title	MK-8291	Placebo
Arm/Group Description	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 a treatment period. (Up to 28 days in each treatment period)	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 a treatment period. (Up to 28 days in each treatment period)
Measure Participants	30	32
Number (95% Confidence Interval) [Percentage of participants]	36.7 203.9%	34.4 202.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-8291, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.073
	Confidence Interval	(2-Sided) 95%; 0.446 to 2.580
	Parameter Dispersion	Type: Value:
	Estimation Comments	Logistic regression model with factors for treatment & baseline pain intensity

Adverse Events

Time Frame	From first dose of study treatment up to 14 days after last dose of study treatment (Up to a total of approximately 80 days)
Adverse Event Reporting Description	All-Cause Mortality Population: All randomized participants. Adverse Events Population: All participants who received at least one dose of study treatment.
Arm/Group Title	MK-8291		Placebo
Arm/Group Description	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 a treatment period. (Up to 28 days in each treatment period)		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 a treatment period. (Up to 28 days in each treatment period)
All Cause Mortality
	MK-8291		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/33 (0%)
Serious Adverse Events
	MK-8291		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/34 (2.9%)		0/33 (0%)
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION	1/34 (2.9%)	1	0/33 (0%)	0
Other (Not Including Serious) Adverse Events
	MK-8291		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/34 (61.8%)		6/33 (18.2%)
Blood and lymphatic system disorders
PANCYTOPENIA	1/34 (2.9%)	1	0/33 (0%)	0
THROMBOCYTOPENIA	0/34 (0%)	0	1/33 (3%)	1
Ear and labyrinth disorders
VERTIGO	1/34 (2.9%)	1	0/33 (0%)	0
Eye disorders
PHOTOPSIA	7/34 (20.6%)	7	0/33 (0%)	0
VISION BLURRED	3/34 (8.8%)	5	0/33 (0%)	0
Gastrointestinal disorders
DRY MOUTH	1/34 (2.9%)	1	0/33 (0%)	0
DYSPEPSIA	0/34 (0%)	0	1/33 (3%)	1
NAUSEA	5/34 (14.7%)	10	1/33 (3%)	1
VOMITING	5/34 (14.7%)	8	0/33 (0%)	0
General disorders
ASTHENIA	3/34 (8.8%)	4	0/33 (0%)	0
CHILLS	0/34 (0%)	0	1/33 (3%)	1
Infections and infestations
CONJUNCTIVITIS	0/34 (0%)	0	1/33 (3%)	1
CYSTITIS	0/34 (0%)	0	1/33 (3%)	1
NASOPHARYNGITIS	0/34 (0%)	0	1/33 (3%)	1
PERIODONTITIS	0/34 (0%)	0	1/33 (3%)	1
RESPIRATORY TRACT INFECTION	0/34 (0%)	0	1/33 (3%)	1
Injury, poisoning and procedural complications
FOOT FRACTURE	1/34 (2.9%)	1	0/33 (0%)	0
Musculoskeletal and connective tissue disorders
BONE PAIN	0/34 (0%)	0	1/33 (3%)	1
Nervous system disorders
BALANCE DISORDER	3/34 (8.8%)	3	1/33 (3%)	1
BURNING SENSATION	1/34 (2.9%)	1	0/33 (0%)	0
DIZZINESS	13/34 (38.2%)	25	1/33 (3%)	1
DYSGEUSIA	1/34 (2.9%)	3	0/33 (0%)	0
HEADACHE	2/34 (5.9%)	3	2/33 (6.1%)	2
SOMNOLENCE	2/34 (5.9%)	2	1/33 (3%)	1
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN	1/34 (2.9%)	1	0/33 (0%)	0
Skin and subcutaneous tissue disorders
PRURITUS	1/34 (2.9%)	1	0/33 (0%)	0
RASH MACULO-PAPULAR	1/34 (2.9%)	1	0/33 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this study 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.