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

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

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

Study Overview

• Status: Completed
• Conditions: Contraception; Ovulation Inhibition; Contraceptives, Oral
• Intervention / Treatment: Drug: EE20/DRSP (BAY86-5300); Drug: EE20/DRSP (YAZ, BAY86-5300)

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.

• Study Type: Interventional
• Enrollment (Actual): 1887
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Montgomery, Alabama, United States, 36116
  • Arizona
    • Chandler, Arizona, United States, 85224
    • Mesa, Arizona, United States, 85213
    • Mesa, Arizona, United States, 85203
    • Phoenix, Arizona, United States, 85031
    • Tempe, Arizona, United States, 85283
    • Tucson, Arizona, United States, 85712
    • Tucson, Arizona, United States, 85741
  • California
    • Anaheim, California, United States, 92801-2811
    • Beverly Hills, California, United States, 90212
    • Pacific Palisades, California, United States, 90272
    • San Diego, California, United States, 92103
    • San Diego, California, United States, 92108
    • Santa Ana, California, United States, 92705
    • Vallejo, California, United States, 94589
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
    • Denver, Colorado, United States, 80218
    • Greenwood Village, Colorado, United States, 80111
    • Littleton, Colorado, United States, 80123
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
  • Florida
    • Boynton Beach, Florida, United States, 33472-2952
    • Brooksville, Florida, United States, 34613
    • Clearwater, Florida, United States, 33759
    • Coral Gables, Florida, United States, 33134
    • Crystal River, Florida, United States, 34429
    • Jacksonville, Florida, United States, 32259
    • Lake Worth, Florida, United States, 33461
    • Miami, Florida, United States, 33186
    • Naples, Florida, United States, 34102
    • North Miami, Florida, United States, 33161
    • Pembroke Pines, Florida, United States, 33024
    • Plantation, Florida, United States, 33313
    • South Miami, Florida, United States, 33143
    • St. Petersburg, Florida, United States, 33709
    • West Palm Beach, Florida, United States, 33409
  • Georgia
    • Atlanta, Georgia, United States, 30328
    • Decatur, Georgia, United States, 30034
  • Idaho
    • Boise, Idaho, United States, 83704
    • Boise, Idaho, United States, 83702
    • Idaho Falls, Idaho, United States, 83404
  • Illinois
    • Champaign, Illinois, United States, 61820
    • Chicago, Illinois, United States, 60612
  • Indiana
    • Newburgh, Indiana, United States, 47630
  • Kansas
    • Wichita, Kansas, United States, 67207
  • Kentucky
    • Lexington, Kentucky, United States, 40509
  • Louisiana
    • Marrero, Louisiana, United States, 70072
  • Michigan
    • Paw Paw, Michigan, United States, 49079
  • Missouri
    • Chesterfield, Missouri, United States, 63017
    • Kansas City, Missouri, United States, 64114
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
  • Nevada
    • Las Vegas, Nevada, United States, 89109
    • Las Vegas, Nevada, United States, 89104
    • LasVegas, Nevada, United States, 89106
  • New Jersey
    • Moorestown, New Jersey, United States, 08057
    • New Brunswick, New Jersey, United States, 08901
  • New York
    • Rochester, New York, United States, 14618
  • North Carolina
    • Durham, North Carolina, United States, 27713
    • New Bern, North Carolina, United States, 28562
    • Winston-Salem, North Carolina, United States, 27103
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
  • Ohio
    • Cleveland, Ohio, United States, 44122
    • Columbus, Ohio, United States, 43213
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
  • Oregon
    • Portland, Oregon, United States, 97239
    • Portland, Oregon, United States, 97239-3011
  • Pennsylvania
    • Jenkintown, Pennsylvania, United States, 19046
    • Philadelphia, Pennsylvania, United States, 19114
    • Pittsburgh, Pennsylvania, United States, 15206
  • South Carolina
    • Columbia, South Carolina, United States, 29201
    • Mt. Pleasant, South Carolina, United States, 29464
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
    • Jackson, Tennessee, United States, 38305-3618
    • Knoxville, Tennessee, United States, 37920
    • Memphis, Tennessee, United States, 38120
    • Nashville, Tennessee, United States, 37203
  • Texas
    • Colleyville, Texas, United States, 76034
    • Corpus Christi, Texas, United States, 78414
    • Dallas, Texas, United States, 75234
    • Houston, Texas, United States, 77054
    • Houston, Texas, United States, 77074
  • Utah
    • West Jordan, Utah, United States, 84088
  • Virginia
    • Richmond, Virginia, United States, 23294
    • Richmond, Virginia, United States, 23233
  • Washington
    • Seattle, Washington, United States, 98105
    • Spokane, Washington, United States, 99207

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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 Names: 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 Names: SH T00186D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pearl Index	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.	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Bleeding Days (Including Spotting Days)	Number of days per participant with bleeding or spotting	Up to 1 year
Number of Bleeding Days (Excluding Spotting Days)	Number of days per participant with bleeding (excluding spotting days)	Up to 1 year
Number of Days With Bleeding (Including and Excluding Spotting) Within 90-day Reference Period 1.	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.	Day 1 to Day 90
Number of Days With Bleeding (Including and Excluding Spotting) Within 90-day Reference Period 2.	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.	Day 91 to Day 180
Number of Days With Bleeding (Including and Excluding Spotting) Within 90-day Reference Period 3	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.	Day 181 to Day 270
Number of Days With Bleeding/ (Including and Excluding Spotting) Within 90-day Reference Period 4	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.	Day 271 to Day 360
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 1	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.	Up to 1 year
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 2	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.	Up to 1 year
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 3	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.	Up to 1 year
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 4	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.	Up to 1 year
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 5	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.	Up to 1 year
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 6	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.	Up to 1 year
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 7	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.	Up to 1 year
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 8	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.	Up to 1 year
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 9	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.	Up to 1 year
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 10	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.	Up to 1 year
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 11	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.	Up to 1 year
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 12	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.	Up to 1 year
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 13	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.	Up to 1 year
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 14	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.	Up to 1 year
Number of Intracyclic Bleeding Days	Intracyclic bleeding was considered any bleeding/spotting that occurred between withdrawal bleedings.	Up to 1 year
Number of Scheduled and Unscheduled Bleeding Days	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.	Up to 1 year
Length of Cycles	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.	Up to 1 year

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Jensen JT, Garie SG, Trummer D, Elliesen J. Bleeding profile of a flexible extended regimen of ethinylestradiol/drospirenone in US women: an open-label, three-arm, active-controlled, multicenter study. Contraception. 2012 Aug;86(2):110-8. doi: 10.1016/j.contraception.2011.12.009. Epub 2012 Jan 26.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: December 3, 2007
• First Submitted That Met QC Criteria: December 3, 2007
• First Posted (Estimate): December 4, 2007

Study Record Updates

• Last Update Posted (Estimate): March 12, 2014
• Last Update Submitted That Met QC Criteria: January 28, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Oral Contraception; Birth Control pill; Healthy women requesting oral contraception; Contraceptive efficacy
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Drospirenone
• Other Study ID Numbers: 91698; 311642 (Other Identifier: Bayer)