Trial Outcomes & Findings for Study on Safety and Efficacy of an Oral Contraceptive in Long Cycles (NCT NCT00266032)
NCT ID: NCT00266032
Last Updated: 2014-11-03
Results Overview
The number of bleeding days per volunteer was calculated by summing up all days with bleeding intensity spotting or worse. The primary evaluation was the comparison of the flexible extended vs the standard regimen for this primary target variable, which was done for data within the first year of treatment only. As no further comparison or testing was done, no multiplicity issue arose.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1166 participants
Primary outcome timeframe
up to 1 year
Results posted on
2014-11-03
Participant Flow
Randomization scheme in the subgroups was 1:1:1 for the 2 centers performing biopsies and measurements of Bone Mineral Density and metabolic parameters (82 subjects per treatment group). The remaining subjects were randomized according to the ratio 4:1:1.
146 subjects failed screening, 96 of these 146 (65.8%) because inclusion or exclusion criteria were not met, 21 (14.4%) due to withdrawal of consent, 17 (11.6%) because of "other" reasons, 11 (7.5%) due to protocol deviations, 1 (0.7%) was lost to follow-up. 32 randomized subjects never took medication.
Participant milestones
| Measure |
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
|
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
|
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
|
|---|---|---|---|
|
Treatment
STARTED
|
691
|
236
|
239
|
|
Treatment
Patients Treated
|
684
|
221
|
229
|
|
Treatment
Patients Treated and in FAS
|
642
|
209
|
216
|
|
Treatment
COMPLETED
|
580
|
172
|
192
|
|
Treatment
NOT COMPLETED
|
111
|
64
|
47
|
|
Open-label Safety Extension
STARTED
|
489
|
129
|
165
|
|
Open-label Safety Extension
COMPLETED
|
448
|
115
|
140
|
|
Open-label Safety Extension
NOT COMPLETED
|
41
|
14
|
25
|
Reasons for withdrawal
| Measure |
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
|
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
|
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
|
|---|---|---|---|
|
Treatment
Adverse Event
|
42
|
26
|
10
|
|
Treatment
Lost to Follow-up
|
19
|
4
|
2
|
|
Treatment
Pregnancy
|
3
|
2
|
2
|
|
Treatment
Protocol Violation
|
6
|
14
|
13
|
|
Treatment
Withdrawal by Subject
|
28
|
13
|
12
|
|
Treatment
patient moved/wish for pregnancy/no need
|
13
|
5
|
8
|
|
Open-label Safety Extension
Adverse Event
|
5
|
0
|
4
|
|
Open-label Safety Extension
Lost to Follow-up
|
2
|
5
|
4
|
|
Open-label Safety Extension
Pregnancy
|
4
|
1
|
2
|
|
Open-label Safety Extension
Protocol Violation
|
1
|
3
|
2
|
|
Open-label Safety Extension
Withdrawal by Subject
|
19
|
3
|
12
|
|
Open-label Safety Extension
patient moved/wish for pregnancy/no need
|
10
|
2
|
1
|
Baseline Characteristics
Study on Safety and Efficacy of an Oral Contraceptive in Long Cycles
Baseline characteristics by cohort
| Measure |
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=642 Participants
3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
|
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=209 Participants
3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
|
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=216 Participants
13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
|
Total
n=1067 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
24.8 years
n=5 Participants
|
24.8 years
n=7 Participants
|
24.3 years
n=5 Participants
|
24.7 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
642 Participants
n=5 Participants
|
209 Participants
n=7 Participants
|
216 Participants
n=5 Participants
|
1067 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
|
|
Body-Mass-Index (BMI)
|
22.541 kg/m²
n=5 Participants
|
22.541 kg/m²
n=7 Participants
|
22.566 kg/m²
n=5 Participants
|
22.546 kg/m²
n=4 Participants
|
PRIMARY outcome
Timeframe: up to 1 yearPopulation: Full Analysis Set (FAS) (reflecting Intention To Treat (ITT) population), all treated subjects with data available, no imputation
The number of bleeding days per volunteer was calculated by summing up all days with bleeding intensity spotting or worse. The primary evaluation was the comparison of the flexible extended vs the standard regimen for this primary target variable, which was done for data within the first year of treatment only. As no further comparison or testing was done, no multiplicity issue arose.
Outcome measures
| Measure |
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=640 Participants
3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
|
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=209 Participants
3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
|
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=215 Participants
13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
|
|---|---|---|---|
|
Number of Days With Bleeding Including Spotting
|
41 days
Standard Deviation 29
|
61 days
Standard Deviation 51
|
66 days
Standard Deviation 27
|
PRIMARY outcome
Timeframe: up to 2 yearsPopulation: Full Analysis Set (reflecting ITT population), all treated subjects, no imputation, including switchers to flexible treatment in second year
Pregnancies with conception date within 4 days after end of study medication were regarded as during treatment.
Outcome measures
| Measure |
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=879 Participants
3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
|
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
|
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
|
|---|---|---|---|
|
Number of Unintended Pregnancies in Yaz Flexible Arm
|
8 pregnancies
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to 2 yearsPopulation: Full Analysis Set (reflecting ITT population), all treated subjects, no imputation, including switchers to flexible treatment in second year
The Pearl Index (PI) is defined as the number of pregnancies per 100 woman years. The 2-year PI was obtained by dividing the number of pregnancies that occurred during the two years of treatment by the time (in 100 women years) that the women were under risk of getting pregnant. 95% confidence interval according to European Medicine Agency Note for guidance on clinical investigation of steroid contraceptives in women.
Outcome measures
| Measure |
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=879 Participants
3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
|
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
|
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
|
|---|---|---|---|
|
Pearl Index
|
0.64 Pregnancies per 100 woman years
Interval 0.28 to 1.26
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to 2 yearsPopulation: Full Analysis Set (reflecting ITT population), all treated subjects, no imputation, including switchers to flexible treatment in second year
Not included in this analysis are pregnancies due to subject failure eg. non-compliance with tablet intake rules.
Outcome measures
| Measure |
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=875 Participants
3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
|
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
|
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
|
|---|---|---|---|
|
Number of Unintended Pregnancies Due to Method Failure
|
7 Pregnancies
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to 2 yearsPopulation: Full Analysis Set (reflecting ITT population), all treated subjects, no imputation, including switchers to flexible treatment in second year
The adjusted Pearl Index was based on pregnancies due to method failures and compliant treatment cycles, i.e. cycle length between 24 and 124 day, pill break not longer than 7 days, and number of pills taken not smaller than 90% of the number of days in that cycle minus 7 days.
Outcome measures
| Measure |
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=875 Participants
3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
|
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
|
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
|
|---|---|---|---|
|
Adjusted Pearl Index
|
0.60 Pregnancies per 100 woman years
Interval 0.24 to 1.24
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 1 yearPopulation: FAS
The number of bleeding days per volunteer was calculated by summing up all days with bleeding intensity light, normal, or heavy.
Outcome measures
| Measure |
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=640 Participants
3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
|
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=209 Participants
3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
|
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=215 Participants
13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
|
|---|---|---|---|
|
Number of Days With Bleeding Excluding Spotting
|
21 Days
Standard Deviation 15
|
24 Days
Standard Deviation 24
|
43 Days
Standard Deviation 20
|
SECONDARY outcome
Timeframe: up to 1 yearPopulation: FAS (reflecting ITT population), all treated subjects, no imputation
For early dropouts and pregnant subjects with an exposure period of less than 1 year but at least 248 days, the number of bleeding/spotting days was normalized to correspond to a 1-year exposure period.
Outcome measures
| Measure |
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=563 Participants
3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
|
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=168 Participants
3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
|
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=189 Participants
13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
|
|---|---|---|---|
|
Number of Bleeding Days During One Year of Treatment in Subjects With at Least 248 Days of Exposure Normalized to 372 Days
|
44 Days
Standard Deviation 29
|
66 Days
Standard Deviation 55
|
71 Days
Standard Deviation 24
|
SECONDARY outcome
Timeframe: up to 1 yearPopulation: FAS (reflecting ITT), all treated subjects, no imputation
The mean number of bleeding / spotting days, spotting-only and bleeding days was analyzed using reference periods of 90 days as recommended by the WHO.
Outcome measures
| Measure |
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=605 Participants
3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
|
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=182 Participants
3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
|
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=203 Participants
13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
|
|---|---|---|---|
|
Number of Bleeding / Spotting Days by 90-day Reference Period
Reference period 1
|
7.2 Days
Standard Deviation 5.5
|
9.0 Days
Standard Deviation 8.6
|
14.6 Days
Standard Deviation 6.1
|
|
Number of Bleeding / Spotting Days by 90-day Reference Period
Reference period 2
|
5.3 Days
Standard Deviation 5.6
|
6.3 Days
Standard Deviation 6.5
|
10.2 Days
Standard Deviation 4.8
|
|
Number of Bleeding / Spotting Days by 90-day Reference Period
Reference period 3
|
4.6 Days
Standard Deviation 4.3
|
5.1 Days
Standard Deviation 5.8
|
9.8 Days
Standard Deviation 4.8
|
|
Number of Bleeding / Spotting Days by 90-day Reference Period
Reference period 4
|
3.9 Days
Standard Deviation 4.5
|
2.6 Days
Standard Deviation 5.6
|
9.5 Days
Standard Deviation 4.9
|
SECONDARY outcome
Timeframe: Up to one yearPopulation: FAS (reflecting ITT), all treated subjects, no imputation
The mean number of bleeding / spotting episodes was analyzed using reference periods of 90 days as recommended by the WHO.
Outcome measures
| Measure |
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=605 Participants
3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
|
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=182 Participants
3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
|
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=203 Participants
13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
|
|---|---|---|---|
|
Number of Bleeding / Spotting Episodes in 90 Day Reference Period
Reference period 1
|
1.7 Episodes
Standard Deviation 1.7
|
2.0 Episodes
Standard Deviation 1.9
|
3.4 Episodes
Standard Deviation 1.2
|
|
Number of Bleeding / Spotting Episodes in 90 Day Reference Period
Reference period 2
|
1.9 Episodes
Standard Deviation 1.5
|
2.1 Episodes
Standard Deviation 1.4
|
3.4 Episodes
Standard Deviation 1.1
|
|
Number of Bleeding / Spotting Episodes in 90 Day Reference Period
Reference period 3
|
1.7 Episodes
Standard Deviation 1.5
|
2.1 Episodes
Standard Deviation 1.8
|
3.2 Episodes
Standard Deviation 1.0
|
|
Number of Bleeding / Spotting Episodes in 90 Day Reference Period
Reference period 4
|
1.5 Episodes
Standard Deviation 1.5
|
1.3 Episodes
Standard Deviation 1.5
|
3.2 Episodes
Standard Deviation 1.0
|
SECONDARY outcome
Timeframe: Up to one yearPopulation: FAS (reflecting ITT), all treated subjects, no imputation
Days with scheduled and unscheduled bleeding were evaluated for extended regimens only. Unscheduled is any bleeding/spotting that occurred while taking active hormones regardless of the duration of intake, unless they occurred after tablet-free interval during days 1-4 of subsequent treatment cycle, or unless they occurred during days 1-7 of first treatment cycle. Scheduled is any bleeding/spotting that occurred during tablet-free interval, regardless of duration of tablet intake, or during next 4 days of subsequent treatment cycle.
Outcome measures
| Measure |
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=640 Participants
3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
|
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=209 Participants
3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
|
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
|
|---|---|---|---|
|
Days With Scheduled Versus Unscheduled Bleeding
Scheduled bleeding
|
23.3 Days
Standard Deviation 14.3
|
14.0 Days
Standard Deviation 5.9
|
—
|
|
Days With Scheduled Versus Unscheduled Bleeding
Unscheduled bleeding
|
17.1 Days
Standard Deviation 17.4
|
46.6 Days
Standard Deviation 48.4
|
—
|
POST_HOC outcome
Timeframe: Up to one yearPopulation: FAS
Pregnancies with conception date during treatment and within 14 days after end of study medication were included.
Outcome measures
| Measure |
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=639 Participants
3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
|
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
|
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
|
|---|---|---|---|
|
Number of Unintended Pregnancies Including Pregnancies Occuring Within 14 Days After End of Study Medication.
|
2 Pregnancies
|
—
|
—
|
POST_HOC outcome
Timeframe: Up to one yearPopulation: FAS
Following an FDA request another PI evaluation was done for the first year of treatment only and taking into consideration also pregnancies with a conception date within 14 days after end of the study medication. Restricting the analysis to the required first year of treatment, it results in this PI estimation.
Outcome measures
| Measure |
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=639 Participants
3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
|
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
|
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
|
|---|---|---|---|
|
Pearl Index (FDA Criteria)
|
0.34 Pregnancies per 100 woman years
Interval 0.04 to 1.23
|
—
|
—
|
Adverse Events
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
Serious events: 19 serious events
Other events: 310 other events
Deaths: 0 deaths
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
Serious events: 7 serious events
Other events: 116 other events
Deaths: 0 deaths
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
Serious events: 3 serious events
Other events: 121 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=642 participants at risk
3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
|
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=209 participants at risk
3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
|
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=216 participants at risk
13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.31%
2/642 • Number of events 2
|
0.00%
0/209
|
0.00%
0/216
|
|
General disorders
Asthenia
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Infections and infestations
Appendicitis
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/642
|
0.48%
1/209 • Number of events 1
|
0.00%
0/216
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/642
|
0.48%
1/209 • Number of events 1
|
0.00%
0/216
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/642
|
0.48%
1/209 • Number of events 1
|
0.00%
0/216
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/642
|
0.48%
1/209 • Number of events 1
|
0.00%
0/216
|
|
Infections and infestations
Vulval abscess
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Infections and infestations
Perineal abscess
|
0.00%
0/642
|
0.48%
1/209 • Number of events 1
|
0.00%
0/216
|
|
Infections and infestations
Gynaecological chlamydia infection
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Injury, poisoning and procedural complications
Concussion
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Injury, poisoning and procedural complications
Fall
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/642
|
0.48%
1/209 • Number of events 1
|
0.00%
0/216
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/642
|
0.48%
1/209 • Number of events 1
|
0.00%
0/216
|
|
Injury, poisoning and procedural complications
Postoperative thrombosis
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Injury, poisoning and procedural complications
Ligament rupture
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder neoplasm
|
0.00%
0/642
|
0.00%
0/209
|
0.46%
1/216 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Focal nodular hyperplasia
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma stage 0
|
0.00%
0/642
|
0.00%
0/209
|
0.46%
1/216 • Number of events 1
|
|
Nervous system disorders
Loss of consciousness
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Renal and urinary disorders
Calculus urinary
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Renal and urinary disorders
Renal colic
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Reproductive system and breast disorders
Ovarian cyst
|
0.16%
1/642 • Number of events 1
|
0.48%
1/209 • Number of events 1
|
0.00%
0/216
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Reproductive system and breast disorders
Pelvic peritoneal adhesions
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Respiratory, thoracic and mediastinal disorders
Nasal polyps
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Skin and subcutaneous tissue disorders
Rash generalised
|
0.00%
0/642
|
0.00%
0/209
|
0.46%
1/216 • Number of events 1
|
|
Vascular disorders
Thrombosis
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Vascular disorders
Deep vein thrombosis
|
0.16%
1/642 • Number of events 1
|
0.00%
0/209
|
0.00%
0/216
|
|
Vascular disorders
Venous insufficiency
|
0.00%
0/642
|
0.48%
1/209 • Number of events 1
|
0.00%
0/216
|
Other adverse events
| Measure |
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=642 participants at risk
3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
|
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=209 participants at risk
3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
|
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
n=216 participants at risk
13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain lower
|
2.2%
14/642 • Number of events 14
|
5.7%
12/209 • Number of events 12
|
2.3%
5/216 • Number of events 7
|
|
Gastrointestinal disorders
Diarrhoea
|
9.3%
60/642 • Number of events 82
|
11.5%
24/209 • Number of events 31
|
10.2%
22/216 • Number of events 28
|
|
Gastrointestinal disorders
Nausea
|
4.2%
27/642 • Number of events 34
|
5.3%
11/209 • Number of events 12
|
5.6%
12/216 • Number of events 18
|
|
Gastrointestinal disorders
Vomiting
|
5.6%
36/642 • Number of events 52
|
5.7%
12/209 • Number of events 15
|
4.2%
9/216 • Number of events 12
|
|
General disorders
Fatigue
|
3.1%
20/642 • Number of events 25
|
3.3%
7/209 • Number of events 8
|
6.0%
13/216 • Number of events 15
|
|
General disorders
Influenza like illness
|
2.0%
13/642 • Number of events 19
|
6.7%
14/209 • Number of events 21
|
8.3%
18/216 • Number of events 22
|
|
Infections and infestations
Cystitis
|
5.1%
33/642 • Number of events 46
|
11.0%
23/209 • Number of events 32
|
6.5%
14/216 • Number of events 20
|
|
Infections and infestations
Gastroenteritis
|
5.3%
34/642 • Number of events 38
|
7.2%
15/209 • Number of events 17
|
6.0%
13/216 • Number of events 14
|
|
Infections and infestations
Influenza
|
3.6%
23/642 • Number of events 29
|
4.8%
10/209 • Number of events 13
|
6.5%
14/216 • Number of events 16
|
|
Infections and infestations
Nasopharyngitis
|
20.1%
129/642 • Number of events 213
|
20.6%
43/209 • Number of events 62
|
24.5%
53/216 • Number of events 83
|
|
Infections and infestations
Sinusitis
|
2.6%
17/642 • Number of events 22
|
6.2%
13/209 • Number of events 17
|
5.1%
11/216 • Number of events 12
|
|
Infections and infestations
Vulvovaginal candidiasis
|
3.9%
25/642 • Number of events 36
|
5.7%
12/209 • Number of events 14
|
5.6%
12/216 • Number of events 21
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.8%
18/642 • Number of events 19
|
5.7%
12/209 • Number of events 13
|
6.0%
13/216 • Number of events 14
|
|
Nervous system disorders
Headache
|
13.7%
88/642 • Number of events 168
|
19.6%
41/209 • Number of events 62
|
22.2%
48/216 • Number of events 76
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
4.8%
31/642 • Number of events 41
|
5.3%
11/209 • Number of events 12
|
6.9%
15/216 • Number of events 22
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
2.5%
16/642 • Number of events 17
|
4.3%
9/209 • Number of events 12
|
5.1%
11/216 • Number of events 17
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bayer Schering Pharma (BSP AG) coordinates publishing of study results. Principal investigators (PIs) provide BSP AG with a draft at least 90 days prior to date of planned submission or presentation. BSP AG shall have 60 days to recommend any changes. BSP AG can prevent or delay publication by informing PIs within 60 days of BSP AG´s receipt of the document about to be published. PIs shall not publish press releases/other public statements about study/study drug without BSP AG´s written consent.
- Publication restrictions are in place
Restriction type: OTHER