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

Phase 3
Completed
Conditions
Contraception
Interventions
Drug: Fixed extended treatment of EE20/DRSP (YAZ, BAY86-5300)
Drug: Flexible (extended) treatment of EE20/DRSP (YAZ, BAY86-5300)
Drug: Standard 24+4 treatment of EE20/DRSP (YAZ, BAY86-5300)
Registration Number
NCT00266032
Lead Sponsor
Bayer
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
1166
Inclusion Criteria
  • Healthy women who desire contraception
  • smokers ≤ 30 Years old
Exclusion Criteria
  • Contraindication against use of hormonal contraceptives

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Fixed extended treatment of EE20/DRSP (YAZ, BAY86-5300)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.
Flexible (extended) treatment of EE20/DRSP (YAZ, BAY86-5300)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.
Standard 24+4 treatment of EE20/DRSP (YAZ, BAY86-5300)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.
Primary Outcome Measures
NameTimeMethod
Number of Unintended Pregnancies in Yaz Flexible Armup to 2 years

Pregnancies with conception date within 4 days after end of study medication were regarded as during treatment.

Adjusted Pearl IndexUp to 2 years

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.

Pearl IndexUp to 2 years

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 Days With Bleeding Including Spottingup to 1 year

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 Due to Method FailureUp to 2 years

Not included in this analysis are pregnancies due to subject failure eg. non-compliance with tablet intake rules.

Secondary Outcome Measures
NameTimeMethod
Number of Days With Bleeding Excluding Spottingup to 1 year

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 Daysup to 1 year

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 Episodes in 90 Day Reference PeriodUp to one year

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 BleedingUp to one year

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.

Number of Bleeding / Spotting Days by 90-day Reference Periodup to 1 year

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.

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