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| ID | Type | Description | Link |
|---|---|---|---|
| MK-6913-004 | Other Identifier | Protocol number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MK-6913 75 mg | Experimental | 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 | Active Comparator | 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 Comparator | 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 | Experimental | MK-6913 25 mg capsule and matching placebo for 17β-estradiol 1 mg tablet once daily for 4 weeks (Stage 2) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-6913 | Drug |
| ||
| 17-β estradiol |
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Merck Sharp & Dohme LLC | Study Director |
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| ID | Type | URL | Comment |
|---|---|---|---|
| CSR Synopsis | View IPD |
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The study was terminated at the end of Stage 1 so no participants entered Stage 2 and no participants received MK-6913 25 mg.
Thirty sites in the United States, Canada, France, Belgium, New Zealand, and Australia received IRB/ERC approval. Of the 354 participants screened for inclusion, 255 participants were excluded during screening (235 participants did not meet specific exclusion criteria). Ninety-nine participants were randomized for the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | MK-6913 75 mg | MK-6913 75 mg and matching placebo for 17β-estradiol 1 mg once daily for 4 weeks |
| FG001 | 17-β Estradiol 1 mg | 17β-estradiol 1 mg and matching placebo for MK-6913 75 mg once daily for 4 weeks |
| FG002 | Placebo | Matching placebo for MK-6913 75 mg and matching placebo for 17β-estradiol 1 mg once daily for 4 weeks |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | MK-6913 75 mg | MK-6913 75 mg and matching placebo for 17β-estradiol 1 mg once daily for 4 weeks |
| BG001 | 17-β Estradiol 1 mg | 17β-estradiol 1 mg and matching placebo for MK-6913 75 mg once daily for 4 weeks |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The Full Analysis Set (FAS) population consists of all randomized participants who receive at least 1 dose of study treatment, have at least 1 post-randomization observation for the analysis endpoint, and have baseline data for those analyses. | Posted | Least Squares Mean | 95% Confidence Interval | Percent change | Baseline and Week 4 |
Up to 6 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MK-6913 75 mg | MK-6913 75 mg and matching placebo for 17β-estradiol 1 mg once daily for 4 weeks |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | Systematic Assessment |
The study was terminated at the end of Stage 1 so no participants entered Stage 2 and no participants received MK-6913 25 mg.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
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|
| Placebo to MK-6913 | Drug |
|
| Placebo to 17-β estradiol | Drug |
|
| MK-6913 25 mg | Drug |
|
| 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 |
| Protocol Violation |
|
| Withdrawal by Subject |
|
| BG002 | Placebo | Matching placebo for MK-6913 75 mg and matching placebo for 17β-estradiol 1 mg once daily for 4 weeks |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | MK-6913 75 mg | MK-6913 75 mg and matching placebo for 17β-estradiol 1 mg once daily for 4 weeks |
| OG001 | 17-β Estradiol 1 mg | 17β-estradiol 1 mg and matching placebo for MK-6913 75 mg once daily for 4 weeks |
| OG002 | Placebo | Matching placebo for MK-6913 75 mg and matching placebo for 17β-estradiol 1 mg once daily for 4 weeks |
|
|
|
| Primary | 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. | The All-Patients-as Treated (APaT) population is all participants who received at least one dose of study drug. | Posted | Number | Participants | Up to 6 weeks |
|
|
|
| Primary | 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. | The APaT population is all participants who received at least one dose of study drug. | Posted | Number | Participants | Up to 4 weeks |
|
|
|
| Secondary | 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. | The Full Analysis Set (FAS) population consists of all randomized participants who receive at least 1 dose of study treatment, have at least 1 post-randomization observation for the analysis endpoint, and have baseline data for those analyses. | Posted | Least Squares Mean | 95% Confidence Interval | Percent change | Baseline and Week 4 |
|
|
|
|
| Secondary | 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). | The Per-Protocol (PP) population excludes participants due to important deviations from the protocol that may substantially affect the results of the primary and key secondary efficacy endpoints. | Posted | Least Squares Mean | 90% Confidence Interval | mIU/mL | Baseline and Week 4 |
|
|
|
|
| 0 |
| 34 |
| 17 |
| 34 |
| EG001 | 17-β Estradiol 1 mg | 17β-estradiol 1 mg and matching placebo for MK-6913 75 mg once daily for 4 weeks | 0 | 32 | 15 | 32 |
| EG002 | Placebo | Matching placebo for MK-6913 75 mg and matching placebo for 17β-estradiol 1 mg once daily for 4 weeks | 0 | 33 | 16 | 33 |
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | Systematic Assessment |
|
| Abdominal tenderness | Gastrointestinal disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
|
| Faecal incontinence | Gastrointestinal disorders | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Chest pain | General disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Irritability | General disorders | Systematic Assessment |
|
| Oedema peripheral | General disorders | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | Systematic Assessment |
|
| Bronchitis | Infections and infestations | Systematic Assessment |
|
| Ear infection | Infections and infestations | Systematic Assessment |
|
| Fungal infection | Infections and infestations | Systematic Assessment |
|
| Influenza | Infections and infestations | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | Systematic Assessment |
|
| Oral herpes | Infections and infestations | Systematic Assessment |
|
| Rhinitis | Infections and infestations | Systematic Assessment |
|
| Sinusitis | Infections and infestations | Systematic Assessment |
|
| Tooth infection | Infections and infestations | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | Systematic Assessment |
|
| Joint sprain | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Blood glucose increased | Investigations | Systematic Assessment |
|
| Crystal urine | Investigations | Systematic Assessment |
|
| Crystal urine present | Investigations | Systematic Assessment |
|
| Liver function test abnormal | Investigations | Systematic Assessment |
|
| Protein urine | Investigations | Systematic Assessment |
|
| Weight increased | Investigations | Systematic Assessment |
|
| Increased appetite | Metabolism and nutrition disorders | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Dupuytren's contracture | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Uterine leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Lethargy | Nervous system disorders | Systematic Assessment |
|
| Migraine | Nervous system disorders | Systematic Assessment |
|
| Poor quality sleep | Nervous system disorders | Systematic Assessment |
|
| Sciatica | Nervous system disorders | Systematic Assessment |
|
| Sinus headache | Nervous system disorders | Systematic Assessment |
|
| Depression | Psychiatric disorders | Systematic Assessment |
|
| Elevated mood | Psychiatric disorders | Systematic Assessment |
|
| Libido increased | Psychiatric disorders | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | Systematic Assessment |
|
| Breast mass | Reproductive system and breast disorders | Systematic Assessment |
|
| Breast pain | Reproductive system and breast disorders | Systematic Assessment |
|
| Breast tenderness | Reproductive system and breast disorders | Systematic Assessment |
|
| Dysfunctional uterine bleeding | Reproductive system and breast disorders | Systematic Assessment |
|
| Nipple pain | Reproductive system and breast disorders | Systematic Assessment |
|
| Pelvic floor muscle weakness | Reproductive system and breast disorders | Systematic Assessment |
|
| Pelvic pain | Reproductive system and breast disorders | Systematic Assessment |
|
| Vaginal haemorrhage | Reproductive system and breast disorders | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Nasal polyps | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Throat irritation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Tonsillar disorder | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Varicose vein | Vascular disorders | Systematic Assessment |
|
The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication guidelines.
| Longitudinal Data Analysis |
LDA model includes terms for treatment, week (Weeks 1, 2 and 4), region, and interaction of treatment by week. |
| 0.264 |
| Difference in the least squares means |
| -11.22 |
| 2-Sided |
| 95 |
| -31.03 |
| 8.59 |
| Superiority or Other |
ANCOVA with terms for treatment, region, stage of the trial, and baseline value as a covariate in PP population only. |
| 0.001 |
| Difference in the LS means |
| -14.52 |
| 2-Sided |
| 90 |
| -21.73 |
| -7.32 |
| Superiority or Other |