Trial Outcomes & Findings for Efficacy and Safety of Two Flexible Extended Regimens of BAY86-5300 (SH T00186D) in Comparison With the Conventional Regimen of YAZ (NCT NCT00567164)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1887 participants

Primary outcome timeframe

Up to 1 year

Results posted on

2014-03-12

Participant Flow

The date of first subject, first visit was 22 Oct 2007. The date of last subject, last visit was 11 Nov 2009.

A total of 2450 subjects were screened ; 563 failed screening. The remaining 1887 subjects were assigned to treatment. Of these, 1864 (98.8%) were in the Full Analysis Set (FAS), ie, study medication was dispensed to them and they had at least 1 post-baseline observation. A total of 1196 (63.4%) subjects completed the study.

Participant milestones

Participant milestones
Measure	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	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.	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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Overall Study STARTED	1421	234	232
Overall Study Subjects Received Treatment	1406	232	226
Overall Study COMPLETED	875	161	160
Overall Study NOT COMPLETED	546	73	72

Reasons for withdrawal

Reasons for withdrawal
Measure	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	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.	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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Overall Study Withdrawal by Subject	171	21	17
Overall Study Protocol Violation	23	4	2
Overall Study Adverse Event	92	13	9
Overall Study Death	0	0	1
Overall Study Lost to Follow-up	202	23	21
Overall Study Pregnancy	20	4	6
Overall Study Primary Reason coded as 'Other'	37	8	16
Overall Study Missing	1	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=1406 Participants 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	Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300) n=232 Participants 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=226 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.	Total n=1864 Participants Total of all reporting groups
Age, Continuous	25.2 years STANDARD_DEVIATION 4.5 • n=5 Participants	26.8 years STANDARD_DEVIATION 6.8 • n=7 Participants	27.3 years STANDARD_DEVIATION 6.4 • n=5 Participants	25.7 years STANDARD_DEVIATION 5.2 • n=4 Participants
Sex: Female, Male Female	1406 Participants n=5 Participants	232 Participants n=7 Participants	226 Participants n=5 Participants	1864 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) treatment arm. Pooled Full Analysis Sets of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) and Regimen no. 2 of EE20/DRSP (BAY86-5300) treatment arms.

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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=1406 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=1638 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Pearl Index	1.65 Pregnancies per 100 years of exposure Interval 0.96 to 2.65	1.92 Pregnancies per 100 years of exposure Interval 1.22 to 2.89	—

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data.

Number of days per participant with bleeding or spotting

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=1317 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=222 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=207 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Number of Bleeding Days (Including Spotting Days)	39.9 Days Standard Deviation 29.6	46.8 Days Standard Deviation 33.1	51.8 Days Standard Deviation 34.6

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data.

Number of days per participant with bleeding (excluding spotting days)

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=1317 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=222 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=207 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Number of Bleeding Days (Excluding Spotting Days)	19.4 Days Standard Deviation 15.7	21.4 Days Standard Deviation 15.6	32.9 Days Standard Deviation 23.5

SECONDARY outcome

Timeframe: Day 1 to Day 90

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data for 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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=1067 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=176 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=169 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Number of Days With Bleeding (Including and Excluding Spotting) Within 90-day Reference Period 1. Including days with spotting	16.6 Days Standard Deviation 12.2	18.5 Days Standard Deviation 12.9	19.7 Days Standard Deviation 9.8
Number of Days With Bleeding (Including and Excluding Spotting) Within 90-day Reference Period 1. Excluding days with spotting	8.3 Days Standard Deviation 6.9	9.1 Days Standard Deviation 7.2	12.6 Days Standard Deviation 6.5

SECONDARY outcome

Timeframe: Day 91 to Day 180

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data for 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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=950 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=161 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=145 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Number of Days With Bleeding (Including and Excluding Spotting) Within 90-day Reference Period 2. Excluding days with spotting	5.1 Days Standard Deviation 5.2	5.4 Days Standard Deviation 5.5	9.7 Days Standard Deviation 6.3
Number of Days With Bleeding (Including and Excluding Spotting) Within 90-day Reference Period 2. Including days with spotting	11.0 Days Standard Deviation 9.7	12.5 Days Standard Deviation 10.5	14.8 Days Standard Deviation 8.0

SECONDARY outcome

Timeframe: Day 181 to Day 270

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data for 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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=863 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=156 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=131 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Number of Days With Bleeding (Including and Excluding Spotting) Within 90-day Reference Period 3 Excluding days with spotting	4.7 Days Standard Deviation 4.8	4.9 Days Standard Deviation 5.0	9.4 Days Standard Deviation 6.5
Number of Days With Bleeding (Including and Excluding Spotting) Within 90-day Reference Period 3 Including days with spotting	10.0 Days Standard Deviation 8.7	11.4 Days Standard Deviation 10.8	14.8 Days Standard Deviation 8.0

SECONDARY outcome

Timeframe: Day 271 to Day 360

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data for 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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=808 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=143 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=112 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Number of Days With Bleeding/ (Including and Excluding Spotting) Within 90-day Reference Period 4 Including days with spotting	9.0 Days Standard Deviation 9.2	9.5 Days Standard Deviation 10.3	13.6 Days Standard Deviation 7.3
Number of Days With Bleeding/ (Including and Excluding Spotting) Within 90-day Reference Period 4 Excluding days with spotting	4.2 Days Standard Deviation 4.8	4.0 Days Standard Deviation 4.8	8.4 Days Standard Deviation 5.5

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data 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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=1124 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=191 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=187 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 1	84.2 Percentage of Participants	83.8 Percentage of Participants	66.8 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data 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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=1025 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=176 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=180 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 2	85.9 Percentage of Participants	84.7 Percentage of Participants	86.7 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data 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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=868 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=154 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=182 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 3	78.6 Percentage of Participants	79.2 Percentage of Participants	84.6 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data 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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=601 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=121 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=161 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 4	73.4 Percentage of Participants	66.1 Percentage of Participants	86.3 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data 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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=368 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=71 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=155 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 5	78.0 Percentage of Participants	69.0 Percentage of Participants	85.8 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data 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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=229 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=43 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=155 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 6	77.7 Percentage of Participants	69.8 Percentage of Participants	85.2 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data 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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=129 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=30 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=144 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 7	78.3 Percentage of Participants	70.0 Percentage of Participants	84.0 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data 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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=78 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=13 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=143 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 8	82.1 Percentage of Participants	69.2 Percentage of Participants	86.7 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data 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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=46 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=10 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=138 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 9	73.9 Percentage of Participants	80.0 Percentage of Participants	85.5 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data 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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=19 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=10 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=130 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 10	78.9 Percentage of Participants	70.0 Percentage of Participants	84.6 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data 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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=9 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=8 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=128 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 11	55.6 Percentage of Participants	62.5 Percentage of Participants	85.9 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data 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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=4 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=3 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=117 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 12	0 Percentage of Participants	33.3 Percentage of Participants	78.6 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data 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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=1 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=73 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 13	0 Percentage of Participants	20.5 Percentage of Participants	—

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding data 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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=11 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Percentage of Participants With a Withdrawal Bleeding Episode for Cycle 14	9.1 Percentage of Participants	—	—

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding and tablet intake data sufficient to calculate intracyclic bleeding.

Intracyclic bleeding was considered any bleeding/spotting that occurred between withdrawal bleedings.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=1222 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=208 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=201 Participants 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Number of Intracyclic Bleeding Days Including spotting only episodes	8.0 Days Standard Deviation 11.8	14.4 Days Standard Deviation 19.1	7.1 Days Standard Deviation 12.7
Number of Intracyclic Bleeding Days Excluding spotting only episodes	3.6 Days Standard Deviation 7.9	7.3 Days Standard Deviation 12.8	5.2 Days Standard Deviation 11.4

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). The number of participants analyzed only includes women who provided bleeding and tablet intake data sufficient to calculate scheduled/unscheduled bleeding. Analysis was only performed for the flexible and stop-and-go extended regimens.

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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=1316 Participants 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=222 Participants Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Number of Scheduled and Unscheduled Bleeding Days Scheduled bleeding days	20.6 Days Standard Deviation 14.1	21.9 Days Standard Deviation 13.9	—
Number of Scheduled and Unscheduled Bleeding Days Unscheduled bleeding days	20.0 Days Standard Deviation 20.4	25.3 Days Standard Deviation 27.8	—

SECONDARY outcome

Timeframe: Up to 1 year

Population: Full Analysis Set (ie, all treated participants). Only cycle data from participants with sufficient data to calculate cycle length are included.

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.

Outcome measures

Outcome measures
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=5575 Cycles 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	Pooled Analysis of Flexible Regimen no. 1 and Regimen no. 2 n=1021 Cycles Pooled FAS of Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) (see first arm) and Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300). Regimen no. 2: 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=2082 Cycles 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Length of Cycles	70.9 Days Standard Deviation 41.3	67.6 Days Standard Deviation 39.1	28.8 Days Standard Deviation 10.8

Adverse Events

Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300)

Serious events: 12 serious events

Other events: 330 other events

Deaths: 0 deaths

Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300)

Serious events: 6 serious events

Other events: 68 other events

Deaths: 0 deaths

Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300)

Serious events: 2 serious events

Other events: 65 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=1406 participants at risk 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	Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300) n=232 participants at risk 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=226 participants at risk 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Gastrointestinal disorders Abdominal pain	0.00% 0/1406	0.43% 1/232 • Number of events 1	0.00% 0/226
Hepatobiliary disorders Cholecystitis acute	0.07% 1/1406 • Number of events 1	0.00% 0/232	0.00% 0/226
Infections and infestations Acute tonsillitis	0.07% 1/1406 • Number of events 1	0.00% 0/232	0.00% 0/226
Infections and infestations Appendicitis	0.14% 2/1406 • Number of events 2	0.00% 0/232	0.00% 0/226
Infections and infestations Diverticulitis	0.00% 0/1406	0.43% 1/232 • Number of events 1	0.00% 0/226
Infections and infestations Gastroenteritis	0.00% 0/1406	0.43% 1/232 • Number of events 1	0.00% 0/226
Infections and infestations Influenza	0.07% 1/1406 • Number of events 1	0.00% 0/232	0.00% 0/226
Infections and infestations Pneumonia	0.07% 1/1406 • Number of events 1	0.00% 0/232	0.00% 0/226
Infections and infestations Pyelonephritis	0.00% 0/1406	0.43% 1/232 • Number of events 1	0.00% 0/226
Infections and infestations Sepsis	0.00% 0/1406	0.43% 1/232 • Number of events 1	0.00% 0/226
Infections and infestations Urinary tract infection	0.00% 0/1406	0.43% 1/232 • Number of events 1	0.00% 0/226
Injury, poisoning and procedural complications Accident	0.00% 0/1406	0.00% 0/232	0.44% 1/226 • Number of events 1
Metabolism and nutrition disorders Dehydration	0.00% 0/1406	0.43% 1/232 • Number of events 1	0.00% 0/226
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.07% 1/1406 • Number of events 1	0.00% 0/232	0.00% 0/226
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/1406	0.43% 1/232 • Number of events 1	0.00% 0/226
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.07% 1/1406 • Number of events 1	0.00% 0/232	0.00% 0/226
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.14% 2/1406 • Number of events 2	0.00% 0/232	0.44% 1/226 • Number of events 1
Psychiatric disorders Depression	0.07% 1/1406 • Number of events 1	0.43% 1/232 • Number of events 1	0.00% 0/226
Renal and urinary disorders Renal failure	0.07% 1/1406 • Number of events 1	0.00% 0/232	0.00% 0/226
Reproductive system and breast disorders Pelvic prolapse	0.07% 1/1406 • Number of events 1	0.00% 0/232	0.00% 0/226

Other adverse events

Other adverse events
Measure	Flexible (Extended) Regimen no. 1 of EE20/DRSP (BAY86-5300) n=1406 participants at risk 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	Flexible (Extended) Regimen no. 2 of EE20/DRSP (BAY86-5300) n=232 participants at risk 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.	Conventional Regimen of EE20/DRSP (YAZ, BAY86-5300) n=226 participants at risk 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 placebo tablets (SH T470PD). 13 withdrawal bleeding episodes during one year of treatment were expected.
Infections and infestations Nasopharyngitis	5.9% 83/1406 • Number of events 95	6.5% 15/232 • Number of events 17	5.8% 13/226 • Number of events 18
Infections and infestations Sinusitis	6.3% 88/1406 • Number of events 103	6.9% 16/232 • Number of events 17	2.7% 6/226 • Number of events 6
Infections and infestations Upper respiratory tract infection	6.6% 93/1406 • Number of events 102	9.9% 23/232 • Number of events 25	11.9% 27/226 • Number of events 31
Reproductive system and breast disorders Cervical dysplasia	7.5% 105/1406 • Number of events 112	9.1% 21/232 • Number of events 22	10.2% 23/226 • Number of events 28

Additional Information

Therapeutic Area Head

BAYER

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Publication of subgroup data and single center data shall not be performed until the complete study has been published. All relevant aspects regarding publication will be part of the contract between the sponsor and the investigator/institution.
Publication restrictions are in place

Restriction type: OTHER