A Double-blind, Randomized, Placebo and Active Controlled, Multicenter Study to Investigate Efficacy and Safety After Oral Administration of 2 and 3 mg ZK 283197, 1 mg 17ß-estradiol and Placebo Once Daily for 8 Weeks in Postmenopausal Women With Hot Flushes
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Bayer
- Enrollment
- 116
- Primary Endpoint
- Relative change in frequency of moderate to severe hot flushes per week between baseline and Week 8 of the treatment phase
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 45 Years to 65 Years (Adult, Older Adult)
- Sex
- Female
- Accepts 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
Arms & Interventions
ZK 283197, 3 mg
Postmenopausal women with hot flushes received 3 mg (3 x 1 mg tablets) ZK 283197, administered orally once daily over 8 weeks
Intervention: BAY 86-5310 (ZK 283197) (Drug)
Matching placebo
Postmenopausal women with hot flushes received placebo (3 tablets) orally once daily over 8 weeks
Intervention: Placebo (Drug)
ZK 283197, 2 mg
Postmenopausal women with hot flushes received 2 mg (2 x 1 mg tablet) ZK 283197 plus 1 placebo tablet, once daily orally over 8 weeks
Intervention: BAY 86-5310 (ZK 283197) (Drug)
17ß-estradiol
Postmenopausal women with hot flushes received 1 mg (2 x 0.5 mg tablet) 17ß-estradiol plus 1 placebo tablet, once daily orally over 8 weeks
Intervention: 17ß-estradiol (Drug)
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Number of participants with adverse events(From Week 1 of treatment until end of Follow-up period (approximately 12 weeks))
- Exposure-response relationship(At week 8)
- 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))
- Cmax(Pre-dose and up to 24 h post-dose (measured between Week 4-8))
- tmax(Pre-dose and up to 24 h post-dose (measured between Week 4-8))
- Cmin(Pre-dose and up to 24 h post-dose (measured between Week 4-8))
- Cave(Pre-dose and up to 24 h post-dose (measured between Week 4-8))
- Vaginal cytology(Between baseline and Week 8)
- Endometrial thickness(Fom baseline to Week 8)
- Endometrial histology(Between baseline and Week 8)