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

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

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.

Study Overview

• Status: Terminated
• Conditions: Women; Moderate to Severe Vasomotor Symptoms in Postmenopausal
• Intervention / Treatment: Drug: MK-6913; Drug: Placebo to 17-β estradiol; Drug: 17-β estradiol; Drug: Placebo to MK-6913; Drug: MK-6913 25 mg

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MK-6913 75 mg; 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; Drug: Placebo to 17-β estradiol
Active Comparator: 17-β estradiol 1 mg; 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; Drug: Placebo to MK-6913
Placebo Comparator: Placebo; 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 17-β estradiol; Drug: Placebo to MK-6913
Experimental: 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)	Drug: MK-6913 25 mg

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2009
• Primary Completion (Actual): July 30, 2010
• Study Completion (Actual): July 30, 2010

Study Registration Dates

• First Submitted: November 17, 2009
• First Submitted That Met QC Criteria: November 17, 2009
• First Posted (Estimate): November 18, 2009

Study Record Updates

• Last Update Posted (Actual): August 31, 2018
• Last Update Submitted That Met QC Criteria: August 1, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate
• Other Study ID Numbers: 6913-004; MK-6913-004 (Other Identifier: Protocol number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis