Efficacy and Safety of Two Flexible Extended Regimens of BAY86-5300 (SH T00186D) in Comparison With the Conventional Regimen of YAZ

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00567164
First received: December 3, 2007
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

The purpose of this study is to determine whether the study drug is safe and effective.


Condition Intervention Phase
Contraception
Ovulation Inhibition
Contraceptives, Oral
Drug: EE20/DRSP (BAY86-5300)
Drug: 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-label, Three-arm, Active-controlled Study to Assess the Efficacy and Safety of the Oral Contraceptive SH T00186D (0.02 mg Ethinyl Estradiol as Betadex Clathrate and 3 mg Drospirenone) in Two Flexible Extended Regimens and a Conventional Regimen of YAZ in 1756 Healthy Females for 1 Year

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Pearl Index [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    The Pearl Index (PI) is the number of pregnancies per 100 woman years. The PI is obtained by dividing the number of pregnancies during treatment (conception date on/after the 1st day of treatment and not later than last day of treatment +14 days) by the treatment exposure time (in 100 women years) that the women were under risk of getting pregnant. The Pearl Index was not calculated individually for either the Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300) treatment arm, nor for the Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) treatment arm, because the low sample size in these treatment arms (approximately. 200 subjects per group) did not allow a reliable PI calculation of these groups alone.


Secondary Outcome Measures:
  • Number of Bleeding Days (Including Spotting Days) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Number of days per participant with bleeding or spotting

  • Number of Bleeding Days (Excluding Spotting Days) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Number of days per participant with bleeding (excluding spotting days)

  • Number of Days With Bleeding (Including and Excluding Spotting) Within 90-day Reference Period 1. [ Time Frame: Day 1 to Day 90 ] [ Designated as safety issue: No ]
    Number of days per participant with bleeding (including and excluding spotting) within 90-day reference period 1. Reference period 1 (Day 1 to Day 90) was a 90 day period starting with the initial intake of study medication (protocol-specified to occur on first day of menstrual or withdrawal bleeding after screening). Therefore, the first 90-day reference period contains additional bleeding days (associated with the menstrual cycle prior to the start of study medication) when compared to any other reference period.

  • Number of Days With Bleeding (Including and Excluding Spotting) Within 90-day Reference Period 2. [ Time Frame: Day 91 to Day 180 ] [ Designated as safety issue: No ]
    Number of days per participant with bleeding (including and excluding spotting) within 90-day reference period 2. Reference period 2 (Day 91 to Day 180) was a 90-day period that started with the intake of study medication at the beginning of Cycle 4.

  • Number of Days With Bleeding (Including and Excluding Spotting) Within 90-day Reference Period 3 [ Time Frame: Day 181 to Day 270 ] [ Designated as safety issue: No ]
    Number of days per participant with bleeding (including and excluding spotting) within 90-day reference period 3. Reference period 3 (Day 181 to Day 270) was a 90-day period that started with the intake of study medication at the beginning of Cycle 7.

  • Number of Days With Bleeding/ (Including and Excluding Spotting) Within 90-day Reference Period 4 [ Time Frame: Day 271 to Day 360 ] [ Designated as safety issue: No ]
    Number of days per participant with bleeding (including and excluding spotting) within 90-day reference period 4. Reference period 4 (Day 271 to Day 360) was a 90-day period that started with the intake of study medication at the beginning of Cycle 10.

  • Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 1 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A withdrawal bleeding episode (WBE) for the two flexible (extended) treatment arms 1) Ended at the earliest 4 days before the first day of the pill break of that cycle or later, AND 2) Started before or at the latest on the 4th day of the next cycle. For the conventional 24+4 treatment arm, a WBE 1) Started on or after Day 21 of that cycle, and lasted at least until Day 25 of the same cycle, OR 2) Started on or after Day 25 of that cycle, but before Day 25 of the next cycle. If more than one episode satisfied the above criteria, the first episode to occur was considered to be the WBE.

  • Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 2 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A withdrawal bleeding episode (WBE) for the two flexible (extended) treatment arms 1) Ended at the earliest 4 days before the first day of the pill break of that cycle or later, AND 2) Started before or at the latest on the 4th day of the next cycle. For the conventional 24+4 treatment arm, a WBE 1) Started on or after Day 21 of that cycle, and lasted at least until Day 25 of the same cycle, OR 2) Started on or after Day 25 of that cycle, but before Day 25 of the next cycle. If more than one episode satisfied the above criteria, the first episode to occur was considered to be the WBE.

  • Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 3 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A withdrawal bleeding episode (WBE) for the two flexible (extended) treatment arms 1) Ended at the earliest 4 days before the first day of the pill break of that cycle or later, AND 2) Started before or at the latest on the 4th day of the next cycle. For the conventional 24+4 treatment arm, a WBE 1) Started on or after Day 21 of that cycle, and lasted at least until Day 25 of the same cycle, OR 2) Started on or after Day 25 of that cycle, but before Day 25 of the next cycle. If more than one episode satisfied the above criteria, the first episode to occur was considered to be the WBE.

  • Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 4 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A withdrawal bleeding episode (WBE) for the two flexible (extended) treatment arms 1) Ended at the earliest 4 days before the first day of the pill break of that cycle or later, AND 2) Started before or at the latest on the 4th day of the next cycle. For the conventional 24+4 treatment arm, a WBE 1) Started on or after Day 21 of that cycle, and lasted at least until Day 25 of the same cycle, OR 2) Started on or after Day 25 of that cycle, but before Day 25 of the next cycle. If more than one episode satisfied the above criteria, the first episode to occur was considered to be the WBE.

  • Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 5 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A withdrawal bleeding episode (WBE) for the two flexible (extended) treatment arms 1) Ended at the earliest 4 days before the first day of the pill break of that cycle or later, AND 2) Started before or at the latest on the 4th day of the next cycle. For the conventional 24+4 treatment arm, a WBE 1) Started on or after Day 21 of that cycle, and lasted at least until Day 25 of the same cycle, OR 2) Started on or after Day 25 of that cycle, but before Day 25 of the next cycle. If more than one episode satisfied the above criteria, the first episode to occur was considered to be the WBE.

  • Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 6 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A withdrawal bleeding episode (WBE) for the two flexible (extended) treatment arms 1) Ended at the earliest 4 days before the first day of the pill break of that cycle or later, AND 2) Started before or at the latest on the 4th day of the next cycle. For the conventional 24+4 treatment arm, a WBE 1) Started on or after Day 21 of that cycle, and lasted at least until Day 25 of the same cycle, OR 2) Started on or after Day 25 of that cycle, but before Day 25 of the next cycle. If more than one episode satisfied the above criteria, the first episode to occur was considered to be the WBE.

  • Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 7 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A withdrawal bleeding episode (WBE) for the two flexible (extended) treatment arms 1) Ended at the earliest 4 days before the first day of the pill break of that cycle or later, AND 2) Started before or at the latest on the 4th day of the next cycle. For the conventional 24+4 treatment arm, a WBE 1) Started on or after Day 21 of that cycle, and lasted at least until Day 25 of the same cycle, OR 2) Started on or after Day 25 of that cycle, but before Day 25 of the next cycle. If more than one episode satisfied the above criteria, the first episode to occur was considered to be the WBE.

  • Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 8 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A withdrawal bleeding episode (WBE) for the two flexible (extended) treatment arms 1) Ended at the earliest 4 days before the first day of the pill break of that cycle or later, AND 2) Started before or at the latest on the 4th day of the next cycle. For the conventional 24+4 treatment arm, a WBE 1) Started on or after Day 21 of that cycle, and lasted at least until Day 25 of the same cycle, OR 2) Started on or after Day 25 of that cycle, but before Day 25 of the next cycle. If more than one episode satisfied the above criteria, the first episode to occur was considered to be the WBE.

  • Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 9 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A withdrawal bleeding episode (WBE) for the two flexible (extended) treatment arms 1) Ended at the earliest 4 days before the first day of the pill break of that cycle or later, AND 2) Started before or at the latest on the 4th day of the next cycle. For the conventional 24+4 treatment arm, a WBE 1) Started on or after Day 21 of that cycle, and lasted at least until Day 25 of the same cycle, OR 2) Started on or after Day 25 of that cycle, but before Day 25 of the next cycle. If more than one episode satisfied the above criteria, the first episode to occur was considered to be the WBE.

  • Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 10 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A withdrawal bleeding episode (WBE) for the two flexible (extended) treatment arms 1) Ended at the earliest 4 days before the first day of the pill break of that cycle or later, AND 2) Started before or at the latest on the 4th day of the next cycle. For the conventional 24+4 treatment arm, a WBE 1) Started on or after Day 21 of that cycle, and lasted at least until Day 25 of the same cycle, OR 2) Started on or after Day 25 of that cycle, but before Day 25 of the next cycle. If more than one episode satisfied the above criteria, the first episode to occur was considered to be the WBE.

  • Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 11 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A withdrawal bleeding episode (WBE) for the two flexible (extended) treatment arms 1) Ended at the earliest 4 days before the first day of the pill break of that cycle or later, AND 2) Started before or at the latest on the 4th day of the next cycle. For the conventional 24+4 treatment arm, a WBE 1) Started on or after Day 21 of that cycle, and lasted at least until Day 25 of the same cycle, OR 2) Started on or after Day 25 of that cycle, but before Day 25 of the next cycle. If more than one episode satisfied the above criteria, the first episode to occur was considered to be the WBE.

  • Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 12 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A withdrawal bleeding episode (WBE) for the two flexible (extended) treatment arms 1) Ended at the earliest 4 days before the first day of the pill break of that cycle or later, AND 2) Started before or at the latest on the 4th day of the next cycle. For the conventional 24+4 treatment arm, a WBE 1) Started on or after Day 21 of that cycle, and lasted at least until Day 25 of the same cycle, OR 2) Started on or after Day 25 of that cycle, but before Day 25 of the next cycle. If more than one episode satisfied the above criteria, the first episode to occur was considered to be the WBE.

  • Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 13 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A withdrawal bleeding episode (WBE) for the two flexible (extended) treatment arms 1) Ended at the earliest 4 days before the first day of the pill break of that cycle or later, AND 2) Started before or at the latest on the 4th day of the next cycle. For the conventional 24+4 treatment arm, a WBE 1) Started on or after Day 21 of that cycle, and lasted at least until Day 25 of the same cycle, OR 2) Started on or after Day 25 of that cycle, but before Day 25 of the next cycle. If more than one episode satisfied the above criteria, the first episode to occur was considered to be the WBE. There were no participants who provided bleeding data for cycle 13 in the Flexible (extended) regimen no.1 of EE20/DRSP (BAY86-5300), although one women did receive 13 cycles of treatment.

  • Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 14 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    A withdrawal bleeding episode (WBE) for the two flexible (extended) treatment arms 1) Ended at the earliest 4 days before the first day of the pill break of that cycle or later, AND 2) Started before or at the latest on the 4th day of the next cycle. For the conventional 24+4 treatment arm, a WBE 1) Started on or after Day 21 of that cycle, and lasted at least until Day 25 of the same cycle, OR 2) Started on or after Day 25 of that cycle, but before Day 25 of the next cycle. If more than one episode satisfied the above criteria, the first episode to occur was considered to be the WBE. There were no participants who received treatment in cycle 14 in the Flexible (extended) regimen no.1 of EE20/DRSP (BAY86-5300). There were no participants who provided bleeding data for cycle 14 in the Flexible (extended) regimen no.2 of EE20/DRSP (BAY86-5300), although one woman did receive 14 cycles of treatment.

  • Number of Intracyclic Bleeding Days [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Intracyclic bleeding was considered any bleeding/spotting that occurred between withdrawal bleedings.

  • Number of Scheduled and Unscheduled Bleeding Days [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Scheduled bleeding is any bleeding/spotting (bl/sp) that occurs during the tablet free interval through the next 4 days of the subsequent treatment cycle. Unscheduled bleeding is any bl/sp that occurs while taking active hormones, except for bl/sp that occurs during the tablet free interval through day 4 of the subsequent treatment cycle or bl/sp on days 1-7 of treatment cycle 1.

  • Length of Cycles [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Cycle length per cycle. For the flexible and stop and go extended treatment arms, a treatment cycle started with the first day of pill intake after a tablet-free interval and ended with the last day of the subsequent tablet-free interval. A tablet-free interval (treatment withdrawal) was defined as at least 3 consecutive days without tablet intake. For the standard 24+4 treatment arm, a new cycle started each time a new blister pack of medication was started.


Enrollment: 1887
Study Start Date: October 2007
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Flexible (extended) regimen no. 1 of EE20/DRSP (BAY86-5300)
Minimum of 3 cycles of treatment, each cycle comprising 120 days (maximum) intended treatment with one tablet daily of BAY86-5300 (SH T00186D) followed by a 4-day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred between days 25 to 120 of the treatment cycle, 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 124-day intended treatment cycle was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment
Drug: EE20/DRSP (BAY86-5300)
Combination tablet containing 0.02 mg ethinyl estradiol as betadex clathrate and 3.0 mg drospirenone
Other Name: SH T00186D
Experimental: Flexible (extended) regimen no. 2 of EE20/DRSP (BAY86-5300)
Minimum of 3 cycles of treatment, each cycle comprising 120 days (maximum) uninterrupted treatment with one tablet daily of BAY86-5300 (SH T00186D) and a 4-day tablet-free interval. Subjects were permitted to schedule their withdrawal bleeding (ie, 4-day tablet-free interval) at any time between days 25 to 120 of the cycle. Subjects had the option to follow the bleeding rules of the flexible (extended) regimen no. 1 of BAY86-5300. The minimum period between 2 tablet-free intervals was 24 days. After each 4-day tablet-free interval, a new 124-day intended treatment cycle was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
Drug: EE20/DRSP (BAY86-5300)
Combination tablet containing 0.02 mg ethinyl estradiol as betadex clathrate and 3.0 mg drospirenone
Other Name: SH T00186D
Active Comparator: Conventional regimen 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 of BAY86-5300 (YAZ, SH T00186D) followed by 4 days of tablets without active substance (together resulting in one cycle of 24+4 standard treatment). 13 withdrawal bleeding episodes during one year of treatment were expected.
Drug: EE20/DRSP (YAZ, BAY86-5300)
Fixed package per cycle containing combination tablets containing 0.02 mg ethinyl estradiol as betadex clathrate and 3.0 mg drospirenone (24 per cycle) + tablets without active substance (4 per cycle)
Other Name: SH T00186D

Detailed Description:

The primary efficacy parameter is the number of observed unintended pregnancy during 1 year of treatment. Secondary efficacy parameter include bleeding parameters and menstrual related symptoms Safety parameters included assessment of adverse events, laboratory evaluations.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

- Healthy women between 18 and 45 requesting oral contraception. Smokers may not exceed 35 years of age.

Exclusion Criteria:

- The use of steroidal oral contraceptives, or any drug that could alter oral contraception metabolism will be prohibited during the study.

  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: NCT00567164

  Show 85 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00567164     History of Changes
Other Study ID Numbers: 91698, 311642
Study First Received: December 3, 2007
Results First Received: October 7, 2013
Last Updated: January 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Bayer:
Oral Contraception
Birth Control pill
Healthy women requesting oral contraception
Contraceptive efficacy

Additional relevant MeSH terms:
Contraceptive Agents
Drospirenone
Ethinyl Estradiol
Cardiovascular Agents
Diuretics
Diuretics, Potassium Sparing
Estrogens
Hormone Antagonists
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Mineralocorticoid Receptor Antagonists
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014