E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Generally healthy, postmenopausal women of age 40 to 65 seeking treatment for hot flushes with last natural menstrual period (LNMP) completed at least 12 months prior to screening (if LNMP is uncertain, the medical monitor or designee may approve a follicle-stimulating hormone [FSH] level; FSH level > 40 mIU/mL will allow enrollment). |
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MedDRA Classification |
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 |
To assess the efficacy and safety of DVS-233 SR compared with placebo for treatment of vasomotor symptoms (VMS) associated with menopause and to compare the bleeding incidence of DVS-233 SR and tibolone. |
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E.2.2 | Secondary objectives of the trial |
To assess the effects of DVS-233 SR and tibolone on changes from baseline in weight, breast pain, and health outcomes indicators (Profile of Mood States [POMS], Greene Climacteric Scale [GCS], and Satisfaction Survey [SS]). |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Generally healthy, postmenopausal women of age 40 to 65 seeking treatment for hot flushes with last natural menstrual period (LNMP) completed at least 12 months prior to screening (if LNMP is uncertain, the medical monitor or designee may approve a follicle-stimulating hormone [FSH] level; FSH level > 40 mIU/mL will allow enrollment). 2. Intact uterus 3. Minimum of 7 moderate to severe hot flushes per day or 50 per week recorded for 7 consecutive days during screening, using the following definitions:· Mild hot flush: sensation of heat without sweating· Moderate hot flush: sensation of heat with sweating, able to continue activity· Severe hot flush: sensation of heat with sweating, causing cessation of activity 4. Subjects must have body mass index (BMI) less than or equal to 34 kg/m2 using the nomograph for BMI 5. In the opinion of the investigator, the subject will comply with the protocol and has a high probability of completing the study |
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E.4 | Principal exclusion criteria |
1. Known hypersensitivity to venlafaxine (Effexor or Effexor XR) or tibolone 2. History, presence or suspicion of estrogen-dependent neoplasia (including endometrial hyperplasia) 3. Undiagnosed vaginal bleeding 4. Malignancy, or treatment for malignancy, within the previous 2 years, with the exception of basal cell carcinoma of the skin or squamous cell carcinoma of the skin. A history of breast cancer, melanoma, or any gynecologic cancer, at any time, excludes the subject 5. Unresolved breast findings (on physical or imaging examinations) suggestive of malignant changes 6. Unresolved cervical cytology smear report of atypical glandular cells (AGC). Unresolved atypical squamous cells (ASC). Cervical cytologic smear report of low-grade squamous intraepithelial lesion (LSIL), or greater, cervical intraepithelial neoplasia (CIN) I or greater, or any reported dysplasia 7. History of a seizure disorder other than a single childhood febrile seizure 8. Active or recent arterial thromboembolic disease (e.g., myocardial infarction or angina) 9. History of cerebrovascular accident, stroke, or transient ischemic attack 10. History of venous thromboembolism (e.g., deep venous thrombosis, pulmonary embolism) 11. History or presence of clinically important hepatic or renal disease or other medical disease that might confound the study or be detrimental to the subject (e.g., clinically important cardiac arrhythmia, clinically important hyponatremia, uncontrolled diabetes, uncontrolled hypertension) 12. Endocrine disease (except for controlled hypothyroidism or diet-controlled diabetes mellitus) 13. Presence of major depressive disorder, bipolar disorder, psychotic disorder or generalized anxiety disorder requiring therapy 14. Gallbladder disease (subjects who have had a cholecystecomy may be enrolled). 15. Persistent elevated blood pressure (greater than 160 mm Hg systolic or greater than 100 mm Hg diastolic). Subjects may not be using more than 2 antihypertensive medications for the treatment of hypertension 16. Known presence of raised intraocular pressure or history of narrow-angle glaucoma 17. Neuro-ocular disorders (e.g., retinal vasculitis) 18. Porphyria 19. Clinically important abnormalities on screening physical examination, electrocardiogram (ECG) or laboratory tests (e.g., fasting total cholesterol greater than 300 mg/dL, fasting triglycerides greater than 300 mg/dL, fasting blood glucose greater than 125 mg/dL, or serum alanine aminotransferase [ALT] or serum aspartate aminotransferase [AST] greater than 1.5 times the upper limit of normal for the laboratory used) 20. Presence of malabsorption disorder 21. Use of oral estrogen-, progestin-, androgen- or selective estrogen receptor modulator (SERM)-containing drug products within 8 weeks prior to screening; use of transdermal hormone products within 8 weeks prior to screening; use of vaginal hormone products (rings, creams, gels) within 4 weeks prior to screening; use of intrauterine progestins within 8 weeks prior to screening; use of progestin implants or estrogen injectables within 3 months prior to screening; use of estrogen pellet or progestin injectables within 6 months prior to screening 22. Use of any investigational drug within 30 days 23. Use of medications thought to relieve VMS within 4 weeks prior to screening, such as aldomet, clonidine, dopaminergic or antidopaminergic drugs (e.g., veralipride), Bellergal (containing belladonna, phenobarbital and ergotamine), gabapentin, herbal remedies or nutritional supplements (e.g., soy-derived or red clover-derived isoflavone, black cohosh, vitamine E [at least 800 IU/day]).24. Use of psychoactive medications within 4 weeks prior to screening such as: SSRIs and SNRIs (e.g., fluoxetine [Prozac], sertraline [Zoloft], paroxetine [Paxil] or venlafaxine [Effexor]); regular use of triptans (e.g., sumatriptan [Imitrex], naratriptan [Amerge], zolmitriptan [Zomig]) or drugs with a similar mechanism of action indicated for the treatment of migraine; use of any monoamine oxidase inhibitors (MAOIs); use of any antidepressant, anxiolytic, antipsychotic, or sedative-hypnotic drugs 25. Enrollment has been closed |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoints are the reduction from baseline in the average daily number of moderate to severe hot flushes and in the average daily severity score at weeks 4 and 12 compared with placebo.The primary safety endpoint is the bleeding incidence, defined as the proportion of subjects experiencing at least one episode of bleeding or spotting during treatment. |
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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 | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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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The end of the trial will be the last visit of the last subject undergiong trial. |
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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 | 10 |
E.8.9.1 | In the Member State concerned days | |
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 | 10 |