Comparison of continuous combined estrogen-progestin regimen in alleviation of estrogen deficiency symptoms of postmenopausal women. A randomized, double-blind, fixed dose, multicentre phase IIIb study of 12 month

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2004-000053-34-CZ
• Date of registration: 11/10/2004
• Prospective Registration: No
• Primary sponsor: Orion Corporation, Orion Pharma, Orionintie,
• Public title: Comparison of continuous combined estrogen-progestin regimen in alleviation of estrogen deficiency symptoms of postmenopausal women. A randomized, double-blind, fixed dose, multicentre phase IIIb study of 12 month
• Scientific title: Comparison of continuous combined estrogen-progestin regimen in alleviation of estrogen deficiency symptoms of postmenopausal women. A randomized, double-blind, fixed dose, multicentre phase IIIb study of 12 month
• Date of first enrolment: 28/07/2004
• Target sample size: 675
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-000053-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Czech Republic

Key inclusion & exclusion criteria

Inclusion criteria:
• signed and dated IC
• Postmenopausal women: = 12 months of spontaneous amenorrhoea or = 6 weeks post-surgical bilateral oophorectomy without hysterectomy at screening
• = 30 moderate to severe hot flushes per week at baseline and/or vasomotor symptoms requiring treatment according to clinical judgement of the investigator
• Wash-out period
- is not needed or
- of 1 wk or longer for prior vaginal hormonal products (rings, creams, gels)
- of 4 wks or longer for prior transdermal estrogen alone or estrogen/progestin products
- of 4 wks or longer for prior oral estrogen and/or estrogen/progestin therapy
- of 8 wks or longer for prior intrauterine progestin therapy
- of 3 months or longer for prior progestin implants and estrogen alone injectable drug therapy
- of 6 months or longer for prior estrogen pellet therapy or progestin injectable drug therapy
• no pathological findings in mammogram obtained within 6 months of screening visit

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) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• 36 months of spontaneous amenorrhea at screening
• pregnancy or breastfeeding
• known or past endometrial hyperplasia or cancer
• known, past, or suspected estrogen-dependent malignant tumours (e.g. breast cancer)
• cervical smear class III-IV according to the Bethesda classification
• undiagnosed uterine bleedings
• previous idiopathic or current venous thromboembolism (deep venous thrombosis, pulmonary embolism)
• active or recent arterial thromboembolic disease (e.g. angina pectoris, myocardial infarction)
• personal or strong family history of thromboembolism or recurrent (= 3) spontaneous abortions
• heart failure (NYHA class III-IV)
• cerebrovascular accidents, stroke or transient ischemic attacks in the subject history
• serious disorders of blood coagulation system
• acute liver disease or a history of liver disease (including cholelithiasis) with clinically significant abnormalities in liver function tests at baseline
• porphyria
• uterine fibroids
• endometriosis
• known hypersensitivity to any component of the preparations
• uncontrolled or poorly controlled hypertension (diastolic BP > 95 mmHg and/or systolic BP > 160 mmHg) despite of antihypertensive treatment
• severe or uncontrolled thyroid disease, e.g. thyreotoxicosis
• impaired renal function with clinically significant elevated serum creatinine concentration
• insulin-dependent diabetes mellitus
• diagnosed psychiatric disorders (e.g. schizophrenia, depression)
• systemic lupus erythematosus (SLE)
• any other treatment for climacteric symptoms
• any treatment for hyperlipidemias
• any treatment affecting sex hormone system (e.g. phytoestrogens like soya)
• suspected alcohol or drug abuse
• suspected poor compliance
• participation in another clinical study within the previous 60 days or during the study
• clinically significant abnormalities in the laboratory assessments at baseline



Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Postmenopausal estrogen replacement regimen is the therapy of choice for the alleviation of climacteric symptoms. During the past few years, continuous-combined hormone replacement therapy (HRT) have become increasingly popular. Lower dose estrogen-progestogen combinations are likely to induce less bleeding disturbances and other adverse effects (AEs) and may therefore improve compliance and allow long-term treatment, necessary, e.g. for the prevention of postmenopausal bone loss.
MedDRA version: 7.0 Level: LLT Classification code 10027304

Intervention(s)

Trade Name: Indivina 1.0 mg/ 2.5 mg
Indivina 1.0 mg/ 5.0 mg
Indivina 2.0 mg/ 5.0 mg
Product Name: Indivina
Pharmaceutical Form: Tablet
Concentration unit: IU/mg international unit(s)/milligram
Concentration type: equal
Concentration number: 1.0, 2.0 E2V-2.5, 5.0 MPA

Primary Outcome(s)

Main Objective: The primary objective of the study is to investigate efficacy and safety of 3 continuous combined regimens of Indivina in alleviation of vasomotor (estrogen deficiency) symptoms in women who are more than 1 year menopausal, by measuring the change in frequency and severity of moderate to severe vasomotor symptoms from baseline to Week 12 vasomotor (estrogen deficiency) symptoms using a self-assessed symptoms diary.

Secondary Objective: The secondary objectives include investigations of bleeding days, vasomotor symptoms, alleviation of other estrogen deficiency symptoms, and quality of life (QoL).

Primary end point(s): The change in frequency and severity of moderate to severe vasomotor symptoms from baseline to Week 12 vasomotor (estrogen deficiency) symptoms using a self-assessed symptoms diary.

Secondary ID(s)

0473081