Study on Safety and Efficacy of an Oral Contraceptive in Long Cycles
A Multicenter, Open, Randomized, Parallel Group Comparison to Assess the Safety and Efficacy of the Oral Contraceptive SH T00186D (0.02 mg Ethinylestradiol as Betadex Clathrate and 3 mg Drospirenone) in Two Variations of an Extended Regimen vs. a Standard Regimen (24 + 4 Days) in 1122 Healthy Female Volunteers for One Year, Followed by a One Year Safety Extension
3 other identifiers
interventional
1,166
3 countries
35
Brief Summary
The purpose of the study is to determine safety and efficacy of long-cycle regimens of an oral contraceptive.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Dec 2005
Typical duration for phase_3
35 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2005
CompletedFirst Submitted
Initial submission to the registry
December 14, 2005
CompletedFirst Posted
Study publicly available on registry
December 15, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2008
CompletedResults Posted
Study results publicly available
March 3, 2010
CompletedNovember 3, 2014
October 1, 2014
2.8 years
December 14, 2005
October 28, 2009
October 27, 2014
Conditions
Outcome Measures
Primary Outcomes (5)
Number of Days With Bleeding Including Spotting
The number of bleeding days per volunteer was calculated by summing up all days with bleeding intensity spotting or worse. The primary evaluation was the comparison of the flexible extended vs the standard regimen for this primary target variable, which was done for data within the first year of treatment only. As no further comparison or testing was done, no multiplicity issue arose.
up to 1 year
Number of Unintended Pregnancies in Yaz Flexible Arm
Pregnancies with conception date within 4 days after end of study medication were regarded as during treatment.
up to 2 years
Pearl Index
The Pearl Index (PI) is defined as the number of pregnancies per 100 woman years. The 2-year PI was obtained by dividing the number of pregnancies that occurred during the two years of treatment by the time (in 100 women years) that the women were under risk of getting pregnant. 95% confidence interval according to European Medicine Agency Note for guidance on clinical investigation of steroid contraceptives in women.
Up to 2 years
Number of Unintended Pregnancies Due to Method Failure
Not included in this analysis are pregnancies due to subject failure eg. non-compliance with tablet intake rules.
Up to 2 years
Adjusted Pearl Index
The adjusted Pearl Index was based on pregnancies due to method failures and compliant treatment cycles, i.e. cycle length between 24 and 124 day, pill break not longer than 7 days, and number of pills taken not smaller than 90% of the number of days in that cycle minus 7 days.
Up to 2 years
Secondary Outcomes (5)
Number of Days With Bleeding Excluding Spotting
up to 1 year
Number of Bleeding Days During One Year of Treatment in Subjects With at Least 248 Days of Exposure Normalized to 372 Days
up to 1 year
Number of Bleeding / Spotting Days by 90-day Reference Period
up to 1 year
Number of Bleeding / Spotting Episodes in 90 Day Reference Period
Up to one year
Days With Scheduled Versus Unscheduled Bleeding
Up to one year
Study Arms (3)
Flexible (extended) treatment of EE20/DRSP (YAZ, BAY86-5300)
EXPERIMENTAL3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
Fixed extended treatment of EE20/DRSP (YAZ, BAY86-5300)
EXPERIMENTAL3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
Standard 24+4 treatment of EE20/DRSP (YAZ, BAY86-5300)
ACTIVE COMPARATOR13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
Interventions
3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
Eligibility Criteria
You may qualify if:
- Healthy women who desire contraception
- smokers ≤ 30 Years old
You may not qualify if:
- Contraindication against use of hormonal contraceptives
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Bayerlead
Study Sites (35)
Unknown Facility
Drummondville, Quebec, J2B 1H8, Canada
Unknown Facility
Montreal, Quebec, H1T 1P6, Canada
Unknown Facility
Pointe-Claire, Quebec, H9R 4S3, Canada
Unknown Facility
Québec, Quebec, G1S 2L6, Canada
Unknown Facility
Shawinigan, Quebec, G9N 2H6, Canada
Unknown Facility
Ste-Foy, Quebec, G1V 4X7, Canada
Unknown Facility
Ettlingen, Baden-Wurttemberg, 76275, Germany
Unknown Facility
Karlsruhe, Baden-Wurttemberg, 76199, Germany
Unknown Facility
Ansbach, Bavaria, 91522, Germany
Unknown Facility
Krumbach, Bavaria, 86381, Germany
Unknown Facility
Nuremberg, Bavaria, 90491, Germany
Unknown Facility
Hamburg, Hamburg, 21073, Germany
Unknown Facility
Dietzenbach, Hesse, 63128, Germany
Unknown Facility
Frankfurt am Main, Hesse, 60322, Germany
Unknown Facility
Frankfurt am Main, Hesse, 60439, Germany
Unknown Facility
Frankfurt am Main, Hesse, 65929, Germany
Unknown Facility
Frankfurt am Main, Hesse, 65936, Germany
Unknown Facility
Mühlheim am Main, Hesse, 63165, Germany
Unknown Facility
Bovenden, Lower Saxony, 37120, Germany
Unknown Facility
Hanover, Lower Saxony, 30459, Germany
Unknown Facility
Osnabrück, Lower Saxony, 49074, Germany
Unknown Facility
Wurzen, Saxony, 04808, Germany
Unknown Facility
Bernburg, Saxony-Anhalt, 06406, Germany
Unknown Facility
Jessen, Saxony-Anhalt, 06917, Germany
Unknown Facility
Magdeburg, Saxony-Anhalt, 39104, Germany
Unknown Facility
Magdeburg, Saxony-Anhalt, 39126, Germany
Unknown Facility
Magdeburg, Saxony-Anhalt, 39130, Germany
Unknown Facility
Berlin, State of Berlin, 10115, Germany
Unknown Facility
Berlin, State of Berlin, 10247, Germany
Unknown Facility
Berlin, State of Berlin, 12435, Germany
Unknown Facility
Berlin, State of Berlin, 13187, Germany
Unknown Facility
Gera, Thuringia, 07545, Germany
Unknown Facility
Jena, Thuringia, 07747, Germany
Unknown Facility
Kahla, Thuringia, 07768, Germany
Unknown Facility
Groningen, 9713 GZ, Netherlands
Related Publications (3)
Klipping C, Duijkers I, Fortier MP, Marr J, Trummer D, Elliesen J. Long-term tolerability of ethinylestradiol 20 mug/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study. J Fam Plann Reprod Health Care. 2012 Apr;38(2):84-93. doi: 10.1136/jfprhc-2011-100214.
PMID: 22454004RESULTKlipping C, Duijkers I, Fortier MP, Marr J, Trummer D, Elliesen J. Contraceptive efficacy and tolerability of ethinylestradiol 20 mug/drospirenone 3 mg in a flexible extended regimen: an open-label, multicentre, randomised, controlled study. J Fam Plann Reprod Health Care. 2012 Apr;38(2):73-83. doi: 10.1136/jfprhc-2011-100213.
PMID: 22454003RESULTReif S, Snelder N, Blode H. Characterisation of the pharmacokinetics of ethinylestradiol and drospirenone in extended-cycle regimens: population pharmacokinetic analysis from a randomised Phase III study. J Fam Plann Reprod Health Care. 2013 Apr;39(2):e1-13. doi: 10.1136/jfprhc-2012-100397.
PMID: 23493606RESULT
Related Links
MeSH Terms
Interventions
Limitations and Caveats
Data for center no. 1148 was included in "all randomized" set of subjects, but not in FAS, as during medical monitoring of laboratory data a suspicion of potential misconduct was found. An audit was made, but the suspicion could not be resolved.
Results Point of Contact
- Title
- Therapeutic Area Head
- Organization
- BAYER
Study Officials
- STUDY DIRECTOR
Bayer Study Director
Bayer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 14, 2005
First Posted
December 15, 2005
Study Start
December 1, 2005
Primary Completion
October 1, 2008
Study Completion
October 1, 2008
Last Updated
November 3, 2014
Results First Posted
March 3, 2010
Record last verified: 2014-10