ZK283197 for Treatment of Vasomotor Symptoms

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00537836
First received: September 28, 2007
Last updated: April 8, 2015
Last verified: April 2015
  Purpose

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 Intervention Phase
Vasomotor System
Drug: BAY 86-5310 (ZK 283197)
Drug: Placebo
Drug: 17ß-estradiol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of participants with adverse events [ Time Frame: From Week 1 of treatment until end of Follow-up period (approximately 12 weeks) ] [ Designated as safety issue: Yes ]
  • Exposure-response relationship [ Time Frame: At week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: From baseline up to 8 weeks ] [ Designated as safety issue: No ]
  • Change from baseline to all treatment weeks in severity and frequency of all hot flushes [ Time Frame: From baseline up to 8 weeks ] [ Designated as safety issue: No ]
  • Trough levels at every visit [ Time Frame: Before 1st administration and at Week 1, 2, 4, 6 and 8 ] [ Designated as safety issue: No ]
  • AUC(0-24h) [ Time Frame: Pre-dose and up to 24 h post-dose (measured between Week 4-8) ] [ Designated as safety issue: No ]
    Area under the curve from administration to 24 h after administration

  • Cmax [ Time Frame: Pre-dose and up to 24 h post-dose (measured between Week 4-8) ] [ Designated as safety issue: No ]
    Maximum serum concentration

  • tmax [ Time Frame: Pre-dose and up to 24 h post-dose (measured between Week 4-8) ] [ Designated as safety issue: No ]
    Time to reach maximum drug concentration

  • Cmin [ Time Frame: Pre-dose and up to 24 h post-dose (measured between Week 4-8) ] [ Designated as safety issue: No ]
    Minimum serum concentration

  • Cave [ Time Frame: Pre-dose and up to 24 h post-dose (measured between Week 4-8) ] [ Designated as safety issue: No ]
    Average serum concentration

  • Vaginal cytology [ Time Frame: Between baseline and Week 8 ] [ Designated as safety issue: Yes ]
    The epithelial maturation index/value and the karyopycnotic index were assessed

  • Endometrial thickness [ Time Frame: Fom baseline to Week 8 ] [ Designated as safety issue: Yes ]
    Transvaginal ultrasound was performed to demonstrate the absence of relevant endometrium growth

  • Endometrial histology [ Time Frame: Between baseline and Week 8 ] [ Designated as safety issue: Yes ]

Enrollment: 116
Study Start Date: October 2007
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   45 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00537836

Locations
Germany
Berlin, Germany, 10115
Berlin, Germany, 13353
Netherlands
Groningen, Netherlands, 9713 GZ
United Kingdom
Cambridge, Cambridgeshire, United Kingdom, CB23 2TN
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00537836     History of Changes
Other Study ID Numbers: 91544, 2007-001791-36, 310781
Study First Received: September 28, 2007
Last Updated: April 8, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Bayer:
Hot flushes
Therapy of hot flushes
17ß-estradiol (E2)
Hormone replacement therapy

Additional relevant MeSH terms:
Estradiol
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Estradiol valerate
Polyestradiol phosphate
Contraceptive Agents
Contraceptive Agents, Female
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2015