A Multicenter, Randomized, Double-Blind, Placebo- And Active-Controlled Study of DVS-233 SR for Treatment of Vasomotor Symptoms Associated with Menopause

• Register: EUCTR
• Last refreshed on: 1 May 2012
• Main ID: EUCTR2004-005022-45-CZ
• Date of registration: 04/05/2005
• Prospective Registration: Yes
• Primary sponsor: Wyeth Research Division of Wyeth Pharmaceuticals Inc. Clinical Research and Development
• Public title: A Multicenter, Randomized, Double-Blind, Placebo- And Active-Controlled Study of DVS-233 SR for Treatment of Vasomotor Symptoms Associated with Menopause
• Scientific title: A Multicenter, Randomized, Double-Blind, Placebo- And Active-Controlled Study of DVS-233 SR for Treatment of Vasomotor Symptoms Associated with Menopause
• Date of first enrolment: 14/06/2005
• Target sample size: 465
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-005022-45
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Czech Republic, Finland, Hungary, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years)
F.1.3.1 Number of subjects for this age range

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, he

Age minimum:
Age maximum:
Gender:
Female: yes
Male:

Health Condition(s) or Problem(s) studied

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).

Intervention(s)

Product Name: Desvenlafaxine succinate SR tablets
Pharmaceutical Form: Tablet
INN or Proposed INN: Desvenlafaxine succinate
CAS Number: 386750-22-7
Current Sponsor code: WY-45233-1
Other descriptive name: DVS-233, ODV
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Tibolone
Product Name: Livial 2.5mg tablets
Pharmaceutical Form: Capsule*
INN or Proposed INN: Tibolone
CAS Number: 5630-53-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: 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.

Secondary Objective: 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]).

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.

Secondary ID(s)

3151A2-321

2004-005022-45-HU