A Study of MK-6913 for the Treatment of Hot Flashes in Postmenopausal Women (6913-004)

Study Overview
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Brief Summary
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This study will assess the safety, tolerability, and efficacy of MK-6913 for the treatment of moderate-to-very-severe vasomotor symptoms (hot flashes or hot flushes) in postmenopausal women. The primary study hypothesis is that one or more doses of MK-6913 will result in a significantly greater reduction from baseline, compared to placebo, in the number of moderate to very severe hot flashes after 4 weeks of treatment.

Official Title
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A Phase IIa, Randomized, Double-Blind, Placebo- and Active-Controlled Study to Examine MK-6913 for the Treatment of Vasomotor Symptoms in Postmenopausal Women

Conditions
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Moderate to Severe Vasomotor Symptoms in Postmenopausal, Women

Intervention / Treatment
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* Drug: MK-6913
* Drug: 17-β estradiol
* Drug: Placebo to MK-6913
* Drug: Placebo to 17-β estradiol
* Drug: MK-6913 25 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Woman with at least 50 moderate to very severe hot flash episodes per week Postmenopausal Between 45 and 60 years of age if naturally menopausal, or between 35 and 60 if she underwent a bilateral oophorectomy Not receiving hormone therapy Has had both a normal mammogram and a normal Pap test in the past 6 months Generally healthy Exclusion Criteria: A history of cancer, except for certain skin cancers Undiagnosed vaginal bleeding or any uterine endometrial disorder Currently uses tobacco products, or has used them in the last 6 months Has human immunodeficiency virus (HIV)

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-6913 75 mg<br>MK-6913 75 mg capsule and matching placebo for 17β-estradiol 1 mg tablet once daily for 4 weeks (Stage 1 and Stage 2) | Drug: MK-6913<br> <br> Drug: Placebo to 17-β estradiol<br> <br> |
| Active Comparator: 17-β estradiol 1 mg<br>17β-estradiol 1 mg tablet and matching placebo for MK-6913 75 mg capsule once daily for 4 weeks (Stage 1 and Stage 2) | Drug: 17-β estradiol<br> <br> Drug: Placebo to MK-6913<br> <br> |
| Placebo Comparator: Placebo<br>Matching placebo for MK-6913 75 mg capsule and matching placebo for 17β-estradiol 1 mg tablet once daily for 4 weeks (Stage 1 and State 2) | Drug: Placebo to MK-6913<br> <br> Drug: Placebo to 17-β estradiol<br> <br> |
| Experimental: MK-6913 25 mg<br>MK-6913 25 mg capsule and matching placebo for 17β-estradiol 1 mg tablet once daily for 4 weeks (Stage 2) | Drug: MK-6913 25 mg<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in the Number of Weekly Moderate to Very Severe Hot Flashes (Excluding Outliers) at Week 4 | Hot flashes were recorded in real time and hot flashes recorded retrospectively in the morning and evening reports in a diary day via the Hot Flash e-diary were summed to determine the total number of hot flashes over a diary day. The total number of weekly moderate or worse hot flashes were calculated as the sum of the total number of hot flashes that occur over a diary week (non-missing diary day), divided by the number of days of diary completion, and multiplied by 7 (standardized week). At least 4 non-missing diary days were required to define the total number of weekly moderate or worse hot flashes. Hot flash data was excluded for participants whose number of moderate to severe hot flashes per week were in the top 1% of number of hot flashes reported to exclude any outlier effect. | Baseline and Week 4 | 
| Number of Participants Who Experienced at Least One or More Adverse Events (AE) | An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. | Up to 6 weeks | 
| Number of Participants Who Discontinued Study Drug Due to an AE | An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. | Up to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in the Weekly Hot Flash Severity Score (Combining Severe and Very Severe Score) at Week 4 | Hot flash severity score is calculated by the sum of: the number of mild hot flashes, 2 times number of moderate hot flashes, 3 times the number of severe hot flashes, and 4 times the number of very severe hot flashes. This sum was standardized to a 7-day week if there were any missing days in the e-diary. The severity of each hot flash was recorded by the Hot Flash e-diary. | Baseline and Week 4 | 
| Change From Baseline in Follicle-stimulating Hormone (FSH) Level at Week 4 | FSH was measured to assess estrogen receptor (ER) selectivity (a biomarker for ERα activity and a pharmacodynamic endpoint). | Baseline and Week 4 |