Study to Evaluate MK-6096 in the Treatment of Painful Diabetic Neuropathy (PDN) in Adults (MK-6096-021)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and effectiveness of MK-6096 in the treatment of painful diabetic neuropathy (PDN) in adults.

Official Title
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A Phase IIa, Multicenter, Double-Blind, Placebo-Controlled, Parallel-Group Clinical Trial to Evaluate the Safety and Efficacy of MK-6096 in Patients With Painful Diabetic Neuropathy

Conditions
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Diabetic Neuropathy, Painful

Intervention / Treatment
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* Drug: MK-6096
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a primary diagnosis of painful diabetic neuropathy (PDN) for at least 6 months. Is able to understand & use an electronic diary to complete daily questionnaires. If female of reproductive potential, agrees to use acceptable contraception from Screening through to at least 2 weeks after last dose of study drug. Is on a stable dose of antihyperglycemic treatment for at least 1 month, with hemoglobin A1C level of no more than 11%. If taking an allowable around-the-clock medication for chronic pain, has been on a stable dose for at least 1 month & agrees to stay on same dose during the study. Agrees to not start therapy with opioids, pregabalin, gabapentin, duloxetine or any other medications used to treat neuropathic pain during the study. Has a regular bedtime of before 1 AM (01:00). Agrees to limit alcohol consumption to no more than 3 drinks a day, with no drinks within 3 hours before bedtime. One drink is defined as: 1) 12 ounces of beer; 2) 4 ounces of wine; or 3) 1 ounce of liquor (80 proof or 40% alcohol). Agrees to limit caffeine consumption to no more than 5 standard 6-oz. cups of caffeinated beverages or no more than 600 mg caffeine a day, with no caffeinated beverages after 4 PM (16:00). Agrees to maintain a relatively consistent level of activity throughout the study. Exclusion Criteria: Is pregnant or breastfeeding, or expects to become pregnant during the study. Expects to donate eggs or sperm during the study or within 90 days after last dose of study drug. Has had ineffective treatment with more than 3 neuropathic pain drugs. Anticipates need for surgery during the study. Has another existing type of pain that is as severe as or greater than the pain under study OR is not able to distinguish the pain under study from another existing pain condition. Has post herpetic neuralgia (PHN); small fiber predominant neuropathy (SFN); idiopathic sensory neuropathy (ISN); complex regional pain syndrome; sensory neuropathies; or pain caused by radiation/chemotherapy/amputation/human immunodeficiency virus (HIV) infection. Has received a nerve block for pain within past 6 weeks. Has a history of pernicious anemia, untreated hypothyroidism, or amputations other than toes. Has a history of narcolepsy, cataplexy, circadian rhythm disorder, parasomnia, sleep-related breathing disorder, restless legs syndrome, periodic limb movement disorder, excessive daytime sleepiness, or difficulty sleeping due to a medical condition (i.e. asthma, Gastroesophageal Reflux Disease (GERD)) other than PDN. Has any history of a neurological disorder, including: seizure disorder, stroke, transient ischemic attack, multiple sclerosis, cognitive impairment, or significant head trauma with sustained loss of consciousness. Has a current evidence or history within past 6 months of unstable cardiovascular disorder, including: acute coronary syndrome; unstable angina; congestive heart failure; cardiogenic syncope; cardiomyopathy; or symptomatic arrhythmia. Has a Body Mass Index (BMI) of more than 40 kg/m^2. Has any of the following: 1) evidence of ongoing depression or suicidality; 2) a lifetime history of bipolar disorder, a psychotic disorder, or posttraumatic stress disorder; 3) a psychiatric condition requiring treatment with a prohibited medication; or 3) other current psychiatric condition that might interfere with ability to participate in the study. Is at imminent risk of self-harm or harm to others. Has a history of substance abuse or dependence. Substances include alcohol, marijuana, hypnotics, other prescription drugs, & drugs of abuse, but exclude nicotine. Has a history of malignant cancer within past 5 years, except for adequately treated basal cell or squamous cell skin cancer or cervical cancer. Has a history of hypersensitivity or reaction to more than 2 chemical classes of drugs, including prescription & over-the-counter medications. Is currently participating or has participated in an investigational study of a compound or device within past 30 days OR is not willing to refrain from participating in another study during this study. Has a history of travel across 3 or more time zones or shift work (permanent night shift or rotating day/night shift work) within past 2 weeks, OR anticipates need to travel across 3 or more time zones during the study. Has donated blood products or had more than 300 mL of blood drawn within past 8 weeks; has received blood products within past 30 days; OR intends to donate or receive blood products during the study. Has previously participated in a study of MK-6096. Is an employee and/or a family member of one of the investigators, study staff, or Merck.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-6096 10 mg→MK-6096 10 mg<br>Participants receive MK-6096 10 mg during run-in once daily for 1 week and receive MK-6096 10 mg once daily for 2 weeks during double-blind treatment period. | Drug: MK-6096<br>* MK-6096 10 mg compressed tablets, taken once daily at bedtime for 14 days.<br>|
| Placebo Comparator: MK-6096→Placebo<br>Participants receive MK-6096 10 mg during run-in once daily for 1 week and receive placebo once daily for 2 weeks during double-blind treatment period. | Drug: MK-6096<br>* MK-6096 10 mg compressed tablets, taken once daily at bedtime for 14 days.<br>Drug: Placebo<br>* Matching compressed tablets, taken once daily at bedtime for 14 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Efficacy Failure (TTEF) - Primary Responders | Participants rated their pain twice daily using a 0 to 10 scale with 0=no pain and 10=worst pain you can imagine. The participant's average evening pain intensity scores over the last 3 days of screening period and of run-in period were defined as the run-in baseline score and treatment baseline score, respectively. A primary responder was defined as a participant who had a ≥30% decrease in treatment baseline score relative to run-in baseline score. Efficacy failure was defined as an occurrence of 3 consecutive days, or 4 days in a row with only one day missing and the other 3 days with a daily evening pain intensity score ≥4 and an increase of ≥30% in daily evening pain intensity score relative to treatment baseline score. The time to efficacy failure for primary responders was summarized. | Day 1 of double-blind treatment phase to the first documented efficacy failure (up to 28 days) | 
| Percentage of Participants Who Experienced 1 or More Adverse Events (AE) | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the drug. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an AE. | up to 42 days (up to 14 days for run-in; up to 28 days for active treatment period) | 
| Percentage of Participants Who Were Discontinued Form the Study Due to an AE | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the drug. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an AE. Adverse Events that were reported as the cause for discontinuation of the study drug were recorded. | up to 7 days for run-in; up to 14 days for active treatment period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TTEF - All Responders | Participants rated their pain twice daily using a 0 to 10 scale with 0=no pain and 10=worst pain you can imagine. The participant's average evening pain intensity scores over the last 3 days of screening period and of run-in period were defined as the run-in baseline score and treatment baseline score, respectively. A responder was defined as a participant who had a ≥20% decrease in treatment baseline score relative to run-in baseline score. Efficacy failure was defined as an occurrence of 3 consecutive days, or 4 days in a row with only one day missing and the other 3 days with a daily evening pain intensity score ≥4 and an increase of ≥20% in daily evening pain intensity score relative to treatment baseline score. The time to efficacy failure for responders was summarized. | Day 1 of double-blind treatment phase to the first documented efficacy failure (up to 28 days) | 
| Change in Pain Intensity Scores - Primary Responders | Participants rated their pain twice daily using a 0 to 10 scale with 0=no pain and 10=worst pain you can imagine. The participant's average evening pain intensity scores over the last 3 days of screening period and of run-in period were defined as the run-in baseline score and treatment baseline score, respectively. A primary responder was defined as a participant who had a ≥30% decrease in treatment baseline score relative to run-in baseline score. The final value was the participant's average evening pain intensity score over the last 3 days of treatment period. The change in the final average evening pain intensity score from treatment baseline was summarized for the primary responders. | End of Single-Blind Period (Baseline) and end of Double-Blind Period | 
| Change in Pain Intensity Scores - All Responders | Participants rated their pain twice daily using a 0 to 10 scale with 0=no pain and 10=worst pain you can imagine. The participant's average evening pain intensity scores over the last 3 days of screening period and of run-in period were defined as the run-in baseline score and treatment baseline score, respectively. A responder was defined as a participant who had a ≥20% decrease in treatment baseline score relative to run-in baseline score. The final value was the participant's average evening pain intensity score over the last 3 days of treatment period. The change in the final average evening pain intensity score from treatment baseline was summarized for the responders. | End of Single-Blind Period (Baseline) and end of Double-Blind Period |