ZK283197 for Treatment of Vasomotor Symptoms

Sponsor

Bayer (Industry)

Overall Status

Completed

CT.gov ID

NCT00537836

Collaborator

(none)

116

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

2.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Vasomotor System	Drug: BAY 86-5310 (ZK 283197) Drug: Placebo Drug: 17ß-estradiol	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

116 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2007

Actual Primary Completion Date :

Dec 1, 2008

Actual Study Completion Date :

Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: BAY 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
Placebo Comparator: Matching placebo Postmenopausal women with hot flushes received placebo (3 tablets) orally once daily over 8 weeks	Drug: Placebo Placebo, once daily p.o. over 8 weeks
Experimental: 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	Drug: BAY 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
Active Comparator: 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	Drug: 17ß-estradiol 1 mg (2 x 0.5 mg tablet) 17ß-estradiol, once daily p.o. over 8 weeks

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]
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
tmax [Pre-dose and up to 24 h post-dose (measured between Week 4-8)]
Time to reach maximum drug concentration
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 65 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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