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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
116
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
Placebo, once daily p.o. over 8 weeks
1 mg (2 x 0.5 mg tablet) 17ß-estradiol, once daily p.o. over 8 weeks
Unnamed facility
Berlin, State of Berlin, Germany
Unnamed facility
Berlin, State of Berlin, Germany
Unnamed facility
Groningen, Netherlands
Unnamed facility
Cambridge, Cambridgeshire, United Kingdom
Relative change in frequency of moderate to severe hot flushes per week between baseline and Week 8 of the treatment phase
Time frame: Between baseline and Week 8 of the treatment phase
Number of participants with adverse events
Time frame: From Week 1 of treatment until end of Follow-up period (approximately 12 weeks)
Exposure-response relationship
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
Time frame: At week 8
Change from baseline to all treatment weeks in frequency and severity of moderate to severe hot flushes
Time frame: From baseline up to 8 weeks
Change from baseline to all treatment weeks in severity and frequency of all hot flushes
Time frame: From baseline up to 8 weeks
Trough levels at every visit
Time frame: Before 1st administration and at Week 1, 2, 4, 6 and 8
AUC(0-24h)
Area under the curve from administration to 24 h after administration
Time frame: Pre-dose and up to 24 h post-dose (measured between Week 4-8)
Cmax
Maximum serum concentration
Time frame: Pre-dose and up to 24 h post-dose (measured between Week 4-8)
tmax
Time to reach maximum drug concentration
Time frame: Pre-dose and up to 24 h post-dose (measured between Week 4-8)
Cmin
Minimum serum concentration
Time frame: Pre-dose and up to 24 h post-dose (measured between Week 4-8)
Cave
Average serum concentration
Time frame: Pre-dose and up to 24 h post-dose (measured between Week 4-8)
Vaginal cytology
The epithelial maturation index/value and the karyopycnotic index were assessed
Time frame: Between baseline and Week 8
Endometrial thickness
Transvaginal ultrasound was performed to demonstrate the absence of relevant endometrium growth
Time frame: Fom baseline to Week 8
Endometrial histology
Time frame: Between baseline and Week 8
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