ZK283197 for Treatment of Vasomotor Symptoms

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

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 Overview

• Status: Completed
• Conditions: Vasomotor System
• Intervention / Treatment: Drug: BAY 86-5310 (ZK 283197); Drug: Placebo; Drug: 17ß-estradiol

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
  • Berlin, Germany, 10115
• Netherlands
  • Groningen, Netherlands, 9713 GZ
• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB23 2TN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events		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	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)	Area under the curve from administration to 24 h after administration	Pre-dose and up to 24 h post-dose (measured between Week 4-8)
Cmax	Maximum serum concentration	Pre-dose and up to 24 h post-dose (measured between Week 4-8)
tmax	Time to reach maximum drug concentration	Pre-dose and up to 24 h post-dose (measured between Week 4-8)
Cmin	Minimum serum concentration	Pre-dose and up to 24 h post-dose (measured between Week 4-8)
Cave	Average serum concentration	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	Between baseline and Week 8
Endometrial thickness	Transvaginal ultrasound was performed to demonstrate the absence of relevant endometrium growth	Fom baseline to Week 8
Endometrial histology		Between baseline and Week 8

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: September 28, 2007
• First Submitted That Met QC Criteria: September 28, 2007
• First Posted (Estimate): October 1, 2007

Study Record Updates

• Last Update Posted (Estimate): April 9, 2015
• Last Update Submitted That Met QC Criteria: April 8, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Hormone replacement therapy; Hot flushes; Therapy of hot flushes; 17ß-estradiol (E2)
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol
• Other Study ID Numbers: 91544; 2007-001791-36 (EudraCT Number); 310781 (Other Identifier: Company internal)