Study on Safety and Efficacy of an Oral Contraceptive in Long Cycles

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00266032
First received: December 14, 2005
Last updated: February 19, 2014
Last verified: February 2014
  Purpose

The purpose of the study is to determine safety and efficacy of long-cycle regimens of an oral contraceptive.


Condition Intervention Phase
Contraception
Drug: Flexible (extended) treatment of EE20/DRSP (YAZ, BAY86-5300)
Drug: Fixed extended treatment of EE20/DRSP (YAZ, BAY86-5300)
Drug: Standard 24+4 treatment of EE20/DRSP (YAZ, BAY86-5300)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Number of Days With Bleeding Including Spotting [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
    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.

  • Number of Unintended Pregnancies in Yaz Flexible Arm [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    Pregnancies with conception date within 4 days after end of study medication were regarded as during treatment.

  • Pearl Index [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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.

  • Number of Unintended Pregnancies Due to Method Failure [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Not included in this analysis are pregnancies due to subject failure eg. non-compliance with tablet intake rules.

  • Adjusted Pearl Index [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Days With Bleeding Excluding Spotting [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
    The number of bleeding days per volunteer was calculated by summing up all days with bleeding intensity light, normal, or heavy.

  • Number of Bleeding Days During One Year of Treatment in Subjects With at Least 248 Days of Exposure Normalized to 372 Days [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
    For early dropouts and pregnant subjects with an exposure period of less than 1 year but at least 248 days, the number of bleeding/spotting days was normalized to correspond to a 1-year exposure period.

  • Number of Bleeding / Spotting Days by 90-day Reference Period [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
    The mean number of bleeding / spotting days, spotting-only and bleeding days was analyzed using reference periods of 90 days as recommended by the WHO.

  • Number of Bleeding / Spotting Episodes in 90 Day Reference Period [ Time Frame: Up to one year ] [ Designated as safety issue: No ]
    The mean number of bleeding / spotting episodes was analyzed using reference periods of 90 days as recommended by the WHO.

  • Days With Scheduled Versus Unscheduled Bleeding [ Time Frame: Up to one year ] [ Designated as safety issue: No ]
    Days with scheduled and unscheduled bleeding were evaluated for extended regimens only. Unscheduled is any bleeding/spotting that occurred while taking active hormones regardless of the duration of intake, unless they occurred after tablet-free interval during days 1-4 of subsequent treatment cycle, or unless they occurred during days 1-7 of first treatment cycle. Scheduled is any bleeding/spotting that occurred during tablet-free interval, regardless of duration of tablet intake, or during next 4 days of subsequent treatment cycle.


Enrollment: 1166
Study Start Date: December 2005
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Flexible (extended) treatment of EE20/DRSP (YAZ, BAY86-5300)
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.
Drug: Flexible (extended) treatment of EE20/DRSP (YAZ, BAY86-5300)
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.
Experimental: Fixed extended treatment of EE20/DRSP (YAZ, BAY86-5300)
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.
Drug: Fixed extended treatment of EE20/DRSP (YAZ, BAY86-5300)
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.
Active Comparator: Standard 24+4 treatment of EE20/DRSP (YAZ, BAY86-5300)
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.
Drug: Standard 24+4 treatment of EE20/DRSP (YAZ, BAY86-5300)
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.

Detailed Description:

The study has previously been posted by Schering AG, Germany. Schering AG, Germany has been renamed to Bayer Schering Pharma AG (BSP AG), Germany.

Bayer Schering Pharma AG, Germany is the sponsor of the trial.

The previously posted secondary Outcome Measure "Parameters of safety and tolerability" has been removed from result posting as it is covered by the Adverse Event section.

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy women who desire contraception
  • smokers ≤ 30 Years old

Exclusion Criteria:

  • Contraindication against use of hormonal contraceptives
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00266032

Locations
Canada, Quebec
Drummondville, Quebec, Canada, J2B 1H8
Montreal, Quebec, Canada, H1T 1P6
Pointe-Claire, Quebec, Canada, H9R 4S3
Shawinigan, Quebec, Canada, G9N 2H6
Ste-Foy, Quebec, Canada, G1V 4X7
Canada
Quebec, Canada, G1S 2L6
Germany
Ettlingen, Baden-Württemberg, Germany, 76275
Karlsruhe, Baden-Württemberg, Germany, 76199
Ansbach, Bayern, Germany, 91522
Krumbach, Bayern, Germany, 86381
Nürnberg, Bayern, Germany, 90491
Dietzenbach, Hessen, Germany, 63128
Frankfurt, Hessen, Germany, 60439
Frankfurt, Hessen, Germany, 65929
Frankfurt, Hessen, Germany, 65936
Frankfurt, Hessen, Germany, 60322
Mühlheim, Hessen, Germany, 63165
Bovenden, Niedersachsen, Germany, 37120
Hannover, Niedersachsen, Germany, 30459
Osnabrück, Niedersachsen, Germany, 49074
Bernburg, Sachsen-Anhalt, Germany, 06406
Jessen, Sachsen-Anhalt, Germany, 06917
Magdeburg, Sachsen-Anhalt, Germany, 39126
Magdeburg, Sachsen-Anhalt, Germany, 39130
Magdeburg, Sachsen-Anhalt, Germany, 39104
Wurzen, Sachsen, Germany, 04808
Gera, Thüringen, Germany, 07545
Jena, Thüringen, Germany, 07747
Kahla, Thüringen, Germany, 07768
Berlin, Germany, 10247
Berlin, Germany, 13187
Berlin, Germany, 12435
Berlin, Germany, 10115
Hamburg, Germany, 21073
Netherlands
Groningen, Netherlands, 9713 GZ
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00266032     History of Changes
Other Study ID Numbers: 91450, 2005-002125-32, 308683
Study First Received: December 14, 2005
Results First Received: October 28, 2009
Last Updated: February 19, 2014
Health Authority: Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Contraceptive Agents
Contraceptives, Oral
Ethinyl Estradiol
Drospirenone
Drospirenone and ethinyl estradiol combination
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Contraceptive Agents, Female
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Aldosterone Antagonists
Hormone Antagonists

ClinicalTrials.gov processed this record on April 23, 2014