Vasomotor System
Conditions
Keywords
Hot flushes, Therapy of hot flushes, 17ß-estradiol (E2), Hormone replacement therapy
Brief summary
The primary goal of the planned study is to investigate the efficacy and safety of ZK 283197 in the dosage of 2 and 3 mg ingested once daily during a period of 8 weeks for the treatment of hot flushes. In order to be able to assess the efficacy of the test substance, this is compared with the efficacy of 1 mg Estradiol and placebo. The comparator Estradiol is a certified hormone preparation, which is already used for the treatment of hot flushes as standard treatment. After passing the screening, volunteers will start with a run-in phase followed by a 8 weeks treatment and a follow-up phase. 112 postmenopausal women with hot flushes and without relevant prior diseases will participate in three European countries (2 study sites in Germany, 1 study site in Great Britain and 1 study site in The Netherlands) in this study.
Interventions
DRUGBAY 86-5310 (ZK 283197)
3 mg (3 x 1 mg tablet) or 2 mg (2 x 1 mg tablet) ZK 283197 in respective treatment group, once daily p.o. over 8 weeks
DRUGPlacebo
Placebo, once daily p.o. over 8 weeks
DRUG17ß-estradiol
1 mg (2 x 0.5 mg tablet) 17ß-estradiol, once daily p.o. over 8 weeks
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Women with at least 35 moderate to severe hot flushes in seven consecutive days * Body mass index (BMI) : 20 - 30 kg/m² (inclusive) * Postmenopausal status
Exclusion criteria
* Contraindication for use for hormonal therapy * Prior hysterectomy * Hormonal therapy or intrauterine hormone releasing device within 4 weeks prior to study entry or any long-acting injectable or implant up to 6 months prior to study entry * Repeated intake of medications affecting study aim
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Relative change in frequency of moderate to severe hot flushes per week between baseline and Week 8 of the treatment phase | Between baseline and Week 8 of the treatment phase |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Exposure-response relationship | At week 8 | A generalized linear model was applied to explore the dependence of the number of hot flushes in Week 8 to (i) the dose of ZK 283197, (ii) the AUC of ZK 283197, (iii) the maximum concentration Cmax of ZK 283197 and (iv) the average concentration Cave of ZK 283197 |
| Change from baseline to all treatment weeks in frequency and severity of moderate to severe hot flushes | From baseline up to 8 weeks | — |
| Change from baseline to all treatment weeks in severity and frequency of all hot flushes | From baseline up to 8 weeks | — |
| Trough levels at every visit | Before 1st administration and at Week 1, 2, 4, 6 and 8 | — |
| AUC(0-24h) | Pre-dose and up to 24 h post-dose (measured between Week 4-8) | Area under the curve from administration to 24 h after administration |
| Cmax | Pre-dose and up to 24 h post-dose (measured between Week 4-8) | Maximum serum concentration |
| Number of participants with adverse events | From Week 1 of treatment until end of Follow-up period (approximately 12 weeks) | — |
| Cmin | Pre-dose and up to 24 h post-dose (measured between Week 4-8) | Minimum serum concentration |
| Cave | Pre-dose and up to 24 h post-dose (measured between Week 4-8) | Average serum concentration |
| Vaginal cytology | Between baseline and Week 8 | The epithelial maturation index/value and the karyopycnotic index were assessed |
| Endometrial thickness | Fom baseline to Week 8 | Transvaginal ultrasound was performed to demonstrate the absence of relevant endometrium growth |
| Endometrial histology | Between baseline and Week 8 | — |
| tmax | Pre-dose and up to 24 h post-dose (measured between Week 4-8) | Time to reach maximum drug concentration |
Countries
Germany, Netherlands, United Kingdom
Outcome results
None listed