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

Phase 2

Terminated

• Conditions: Moderate to Severe Vasomotor Symptoms in Postmenopausal; Women
• Interventions: Drug: MK-6913; Drug: 17-β estradiol; Drug: MK-6913 25 mg; Drug: Placebo to 17-β estradiol; Drug: Placebo to MK-6913

• Registration Number: NCT01015677
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-11-17
• Study First Submitted QC: 2009-11-17
• Study First Posted: 2009-11-18
• Study Start: 2009-12-17
• Primary Completion: 2010-07-30
• Study Completion: 2010-07-30
• Results First Submitted: 2016-02-26
• Results First Submitted QC: 2016-04-01
• Results First Posted: 2016-05-04
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-01
• Last Update Posted: 2018-08-31

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 99

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MK-6913 75 mg	MK-6913	MK-6913 75 mg capsule and matching placebo for 17β-estradiol 1 mg tablet once daily for 4 weeks (Stage 1 and Stage 2)
MK-6913 75 mg	Placebo to 17-β estradiol	MK-6913 75 mg capsule and matching placebo for 17β-estradiol 1 mg tablet once daily for 4 weeks (Stage 1 and Stage 2)
17-β estradiol 1 mg	17-β estradiol	17β-estradiol 1 mg tablet and matching placebo for MK-6913 75 mg capsule once daily for 4 weeks (Stage 1 and Stage 2)
17-β estradiol 1 mg	Placebo to MK-6913	17β-estradiol 1 mg tablet and matching placebo for MK-6913 75 mg capsule once daily for 4 weeks (Stage 1 and Stage 2)
Placebo	Placebo to MK-6913	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)
Placebo	Placebo to 17-β estradiol	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)
MK-6913 25 mg	MK-6913 25 mg	MK-6913 25 mg capsule and matching placebo for 17β-estradiol 1 mg tablet once daily for 4 weeks (Stage 2)

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Experienced at Least One or More Adverse Events (AE)	Up to 6 weeks	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.
Number of Participants Who Discontinued Study Drug Due to an AE	Up to 4 weeks	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.
Percent Change From Baseline in the Number of Weekly Moderate to Very Severe Hot Flashes (Excluding Outliers) at Week 4	Baseline and 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.

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline in the Weekly Hot Flash Severity Score (Combining Severe and Very Severe Score) at Week 4	Baseline and 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.
Change From Baseline in Follicle-stimulating Hormone (FSH) Level at Week 4	Baseline and Week 4	FSH was measured to assess estrogen receptor (ER) selectivity (a biomarker for ERα activity and a pharmacodynamic endpoint).