Postherpetic Neuralgia
Conditions
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.
Interventions
DRUGMK-8291
MK-8291 oral tablets
DRUGPlacebo
Placebo oral tablets
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
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.
Participants by arm
| Arm | Count |
|---|---|
| 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) | 18 |
| 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) | 17 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 (28 Days) | Physician Decision | 2 | 0 |
| Treatment Period 1 (28 Days) | Withdrawal by Subject | 0 | 1 |
| Treatment Period 2 (28 Days) | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | MK-8291 → Placebo | Placebo → MK-8291 | Total |
|---|---|---|---|
| Age, Continuous | 56.7 Years STANDARD_DEVIATION 16.7 | 54.7 Years STANDARD_DEVIATION 13.5 | 55.7 Years STANDARD_DEVIATION 15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 17 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Numerical Rating Scale (NRS) Pain Intesity Score at Baseline | 6.63 Score on a scale STANDARD_DEVIATION 1.02 | 6.00 Score on a scale STANDARD_DEVIATION 0.97 | 6.31 Score on a scale STANDARD_DEVIATION 1.03 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 17 Participants | 35 Participants |
| Sex: Female, Male Female | 11 Participants | 14 Participants | 25 Participants |
| Sex: Female, Male Male | 7 Participants | 3 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 33 |
| other Total, other adverse events | 21 / 34 | 6 / 33 |
| serious Total, serious adverse events | 1 / 34 | 0 / 33 |
Outcome results
Primary
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.
Time frame: Baseline and Days 22-28 of each treatment period (Up to approximately 63 days)
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| MK-8291 | Change From Baseline in Pain Intensity at Week 4 of Each Treatment Period | -1.776 Score on a scale |
| Placebo | Change From Baseline in Pain Intensity at Week 4 of Each Treatment Period | -1.263 Score on a scale |
p-value: 0.07595% CI: [-1.076, 0.172]Linear mixed model
Secondary
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.
Time frame: Baseline and Day 28 in each treatment period (Up to approximately 63 days)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| MK-8291 | Percentage of Participants Achieving a 30 Percent or Greater Change From Baseline to Day 28 in Pain Intensity | 36.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving a 30 Percent or Greater Change From Baseline to Day 28 in Pain Intensity | 34.4 Percentage of participants |
95% CI: [0.446, 2.58]