E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Vasomotor symptoms, specifically hot flushes, that are classic symptoms of estrogen withdrawal associated with menopause. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020411 |
E.1.2 | Term | Hot flushes menopausal |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020417 |
E.1.2 | Term | Hot flushes, menopausal |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027301 |
E.1.2 | Term | Menopausal hot flushes |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To assess the effect of 4 weeks of treatment with MK-6913 on percent change from baseline in weekly frequency of hot flashes of moderate or greater severity. Hypothesis: 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.
2. To assess the safety and tolerability of 4 weeks of treatment with MK-6913. |
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E.2.2 | Secondary objectives of the trial |
1. To assess the effect of 4 weeks of treatment with MK-6913 on percent change from baseline in weekly hot flash severity score.
2. To assess the effect of 4 weeks of treatment with MK-6913 on reduction in FSH.
3. To assess the effect of 4 weeks of treatment with 17β-estradiol 1 mg versus placebo on weekly hot flash frequency and severity score.
4. To compare the effect of 4 weeks of treatment with MK-6913 versus 1 mg 17β-estradiol on weekly hot flash frequency and severity score.
5. To assess the effect of 4 weeks of treatment with MK-6913 on serum lipid parameters. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient is a woman with ≥ 50 moderate-to-very severe hot flash episodes per week. 2. Patient is postmenopausal and is ≥45 and ≤60 years of age (if naturally menopausal) or ≥35 and ≤60 years of age (if surgically menopausal) 3. Patient had at least 6 months of spontaneous amenorrhea AND a serum FSH level >40 mIU/mL at the time of Visit 1 OR has undergone a bilateral oophorectomy at least 6 weeks prior to Visit 1, and a serum FSH level of >40 mIU/mL 4. Patient is not receiving hormone therapy (estrogen alone or estrogen/progestin) 5. Patient has a body mass index (BMI) of ≥18 and ≤40 kg/m2 6. Patient is generally healthy 7. Patient has had a recent normal mammogram and a normal Papanicoloau (Pap) smear test (within 6 months of the Screening)
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E.4 | Principal exclusion criteria |
1. Patient has a history of malignancy ≤ 5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer 2. Patient has any history of breast cancer 3. Patient has history of deep vein thrombosis (DVT), myocardial infarction (MI), stroke, chronic liver disease, gallbladder disorder, chronic renal, cardiac and endocrine diseases 4. Patient has undiagnosed vaginal bleeding, or has any type of uterine endometrial disorders 5. Patient has human immunodeficiency virus (HIV) infection and/or is being treated for HIV 6. Patient is currently a regular user or a recent past abuser of alcohol or illicit drugs 7. Patient has any contraindication for taking 17β-estradiol. 8. Patient has uncontrolled hypertension 9. Patient is currently taking medications which may reduce hot flashes (including OTC products and herbal remedies), as well as agents listed in protocol Appendix 6.7 10. Patient is taking a statin or other lipid lowering agent, unless the patient has been on a stable dose of the lipid lowering agent for at least 6 months 11. Patient has donated blood products within 4 weeks of signing informed consent 12. Patient was <80% compliant with e-diary completion during the 14-day placebo run-in period |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is percentage reduction in the number of hot flashes on week 4 compared to baseline, as recorded by the e-diary. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Provided in the protocol. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 15 |