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Trial record 7 of 23 for:    betadex

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

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ClinicalTrials.gov Identifier: NCT00266032
Recruitment Status : Completed
First Posted : December 15, 2005
Results First Posted : March 3, 2010
Last Update Posted : November 3, 2014
Sponsor:
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Contraception
Interventions Drug: Flexible (extended) treatment of EE20/DRSP (YAZ, BAY86-5300)
Drug: Fixed extended treatment of EE20/DRSP (YAZ, BAY86-5300)
Drug: Standard 24+4 treatment of EE20/DRSP (YAZ, BAY86-5300)
Enrollment 1166
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300) Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300) Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
Hide Arm/Group Description 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. 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. 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.
Period Title: Treatment
Started 691 [1] 236 [1] 239 [1]
Patients Treated 684 221 229
Patients Treated and in FAS 642 [2] 209 [2] 216 [2]
Completed 580 [3] 172 [3] 192 [3]
Not Completed 111 64 47
Reason Not Completed
Adverse Event             42             26             10
Lost to Follow-up             19             4             2
Pregnancy             3             2             2
Protocol Violation             6             14             13
Withdrawal by Subject             28             13             12
patient moved/wish for pregnancy/no need             13             5             8
[1]
all randomized subjects, baseline data for full analysis set (FAS) only
[2]
FAS
[3]
not all entered period 2 (open-label safety extension)
Period Title: Open-label Safety Extension
Started 489 [1] 129 [2] 165 [3]
Completed 448 115 140
Not Completed 41 14 25
Reason Not Completed
Adverse Event             5             0             4
Lost to Follow-up             2             5             4
Pregnancy             4             1             2
Protocol Violation             1             3             2
Withdrawal by Subject             19             3             12
patient moved/wish for pregnancy/no need             10             2             1
[1]
treatment for subjects of all 3 treatment groups in 2nd period, except for 28 in subgroups
[2]
7 subjects continued their treatment in second period (safety extension)
[3]
21 subjects continued their treatment in second period (safety extension)
Arm/Group Title Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300) Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300) Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300) Total
Hide Arm/Group Description 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. 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. 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 of all reporting groups
Overall Number of Baseline Participants 642 209 216 1067
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 642 participants 209 participants 216 participants 1067 participants
24.8
(18 to 35)
24.8
(18 to 35)
24.3
(18 to 35)
24.7
(18 to 35)
[1]
Measure Description: Number of Participants analyzed for baseline was Full Analysis Set (FAS=safety set)
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 642 participants 209 participants 216 participants 1067 participants
Female
642
 100.0%
209
 100.0%
216
 100.0%
1067
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: Number of Participants analyzed for baseline was Full Analysis Set (FAS=safety set)
Body-Mass-Index (BMI)   [1] 
Mean (Full Range)
Unit of measure:  Kg/m²
Number Analyzed 642 participants 209 participants 216 participants 1067 participants
22.541
(17.95 to 30.50)
22.541
(18.00 to 29.70)
22.566
(17.90 to 29.80)
22.546
(17.90 to 30.50)
[1]
Measure Description:

Body mass index was calculated with body weight and height measured at screening (BMI = body weight in kg²/ body height in m³) and had to be 18 Years to 35 Years old (smokers ≤ 30 Years old) at inclusion.

Number of Participants analyzed for baseline was Full Analysis Set (FAS=safety set).

1.Primary Outcome
Title Number of Days With Bleeding Including Spotting
Hide Description 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.
Time Frame up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) (reflecting Intention To Treat (ITT) population), all treated subjects with data available, no imputation
Arm/Group Title Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300) Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300) Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 640 209 215
Mean (Standard Deviation)
Unit of Measure: days
41  (29) 61  (51) 66  (27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300), Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
Comments Primary variable was tested for the hypothesis, whether the means are equal against the alternative (means are different) at a level of significance of alpha = 0.05 (t-test). For power calculation, a normal distribution, a absolute difference of 10 days, a Standard Deviation of 28 days and a drop-out rate of 40% was assumed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -25
Confidence Interval 95%
-29 to -20
Parameter Dispersion
Type: Standard Deviation
Value: 29
Estimation Comments Mean of Yaz flexible regimen minus mean of Yaz standard was tested
2.Primary Outcome
Title Number of Unintended Pregnancies in Yaz Flexible Arm
Hide Description Pregnancies with conception date within 4 days after end of study medication were regarded as during treatment.
Time Frame up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (reflecting ITT population), all treated subjects, no imputation, including switchers to flexible treatment in second year
Arm/Group Title Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 879
Measure Type: Number
Unit of Measure: pregnancies
8
3.Primary Outcome
Title Pearl Index
Hide Description 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.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (reflecting ITT population), all treated subjects, no imputation, including switchers to flexible treatment in second year
Arm/Group Title Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 879
Mean (95% Confidence Interval)
Unit of Measure: Pregnancies per 100 woman years
0.64
(0.28 to 1.26)
4.Primary Outcome
Title Number of Unintended Pregnancies Due to Method Failure
Hide Description Not included in this analysis are pregnancies due to subject failure eg. non-compliance with tablet intake rules.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (reflecting ITT population), all treated subjects, no imputation, including switchers to flexible treatment in second year
Arm/Group Title Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 875
Measure Type: Number
Unit of Measure: Pregnancies
7
5.Primary Outcome
Title Adjusted Pearl Index
Hide Description 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.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (reflecting ITT population), all treated subjects, no imputation, including switchers to flexible treatment in second year
Arm/Group Title Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 875
Mean (95% Confidence Interval)
Unit of Measure: Pregnancies per 100 woman years
0.60
(0.24 to 1.24)
6.Secondary Outcome
Title Number of Days With Bleeding Excluding Spotting
Hide Description The number of bleeding days per volunteer was calculated by summing up all days with bleeding intensity light, normal, or heavy.
Time Frame up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300) Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300) Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 640 209 215
Mean (Standard Deviation)
Unit of Measure: Days
21  (15) 24  (24) 43  (20)
7.Secondary Outcome
Title Number of Bleeding Days During One Year of Treatment in Subjects With at Least 248 Days of Exposure Normalized to 372 Days
Hide Description 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.
Time Frame up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (reflecting ITT population), all treated subjects, no imputation
Arm/Group Title Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300) Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300) Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 563 168 189
Mean (Standard Deviation)
Unit of Measure: Days
44  (29) 66  (55) 71  (24)
8.Secondary Outcome
Title Number of Bleeding / Spotting Days by 90-day Reference Period
Hide Description 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.
Time Frame up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (reflecting ITT), all treated subjects, no imputation
Arm/Group Title Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300) Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300) Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 605 182 203
Mean (Standard Deviation)
Unit of Measure: Days
Reference period 1 7.2  (5.5) 9.0  (8.6) 14.6  (6.1)
Reference period 2 5.3  (5.6) 6.3  (6.5) 10.2  (4.8)
Reference period 3 4.6  (4.3) 5.1  (5.8) 9.8  (4.8)
Reference period 4 3.9  (4.5) 2.6  (5.6) 9.5  (4.9)
9.Secondary Outcome
Title Number of Bleeding / Spotting Episodes in 90 Day Reference Period
Hide Description The mean number of bleeding / spotting episodes was analyzed using reference periods of 90 days as recommended by the WHO.
Time Frame Up to one year
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (reflecting ITT), all treated subjects, no imputation
Arm/Group Title Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300) Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300) Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 605 182 203
Mean (Standard Deviation)
Unit of Measure: Episodes
Reference period 1 1.7  (1.7) 2.0  (1.9) 3.4  (1.2)
Reference period 2 1.9  (1.5) 2.1  (1.4) 3.4  (1.1)
Reference period 3 1.7  (1.5) 2.1  (1.8) 3.2  (1.0)
Reference period 4 1.5  (1.5) 1.3  (1.5) 3.2  (1.0)
10.Secondary Outcome
Title Days With Scheduled Versus Unscheduled Bleeding
Hide Description 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.
Time Frame Up to one year
Hide Outcome Measure Data
Hide Analysis Population Description
FAS (reflecting ITT), all treated subjects, no imputation
Arm/Group Title Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300) Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 640 209
Mean (Standard Deviation)
Unit of Measure: Days
Scheduled bleeding 23.3  (14.3) 14.0  (5.9)
Unscheduled bleeding 17.1  (17.4) 46.6  (48.4)
11.Post-Hoc Outcome
Title Number of Unintended Pregnancies Including Pregnancies Occuring Within 14 Days After End of Study Medication.
Hide Description Pregnancies with conception date during treatment and within 14 days after end of study medication were included.
Time Frame Up to one year
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 639
Measure Type: Number
Unit of Measure: Pregnancies
2
12.Post-Hoc Outcome
Title Pearl Index (FDA Criteria)
Hide Description 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.
Time Frame Up to one year
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 639
Mean (95% Confidence Interval)
Unit of Measure: Pregnancies per 100 woman years
0.34
(0.04 to 1.23)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300) Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300) Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
Hide Arm/Group Description 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. 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. 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.
All-Cause Mortality
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300) Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300) Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300) Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300) Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/642 (2.96%)      7/209 (3.35%)      3/216 (1.39%)    
Gastrointestinal disorders       
Abdominal pain * 1  2/642 (0.31%)  2 0/209 (0.00%)  0 0/216 (0.00%)  0
General disorders       
Asthenia * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Infections and infestations       
Appendicitis * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Gastroenteritis * 1  0/642 (0.00%)  0 1/209 (0.48%)  1 0/216 (0.00%)  0
Pyelonephritis * 1  0/642 (0.00%)  0 1/209 (0.48%)  1 0/216 (0.00%)  0
Tonsillitis * 1  0/642 (0.00%)  0 1/209 (0.48%)  1 0/216 (0.00%)  0
Urinary tract infection * 1  0/642 (0.00%)  0 1/209 (0.48%)  1 0/216 (0.00%)  0
Vulval abscess * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Perineal abscess * 1  0/642 (0.00%)  0 1/209 (0.48%)  1 0/216 (0.00%)  0
Gynaecological chlamydia infection * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Injury, poisoning and procedural complications       
Concussion * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Fall * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Foot fracture * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Road traffic accident * 1  0/642 (0.00%)  0 1/209 (0.48%)  1 0/216 (0.00%)  0
Contusion * 1  0/642 (0.00%)  0 1/209 (0.48%)  1 0/216 (0.00%)  0
Postoperative thrombosis * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Ligament rupture * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Intervertebral disc protrusion * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Bladder neoplasm * 1  0/642 (0.00%)  0 0/209 (0.00%)  0 1/216 (0.46%)  1
Uterine leiomyoma * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Focal nodular hyperplasia * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Cervix carcinoma stage 0 * 1  0/642 (0.00%)  0 0/209 (0.00%)  0 1/216 (0.46%)  1
Nervous system disorders       
Loss of consciousness * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Renal and urinary disorders       
Calculus urinary * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Renal colic * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Reproductive system and breast disorders       
Ovarian cyst * 1  1/642 (0.16%)  1 1/209 (0.48%)  1 0/216 (0.00%)  0
Pelvic pain * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Pelvic peritoneal adhesions * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Nasal polyps * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Skin and subcutaneous tissue disorders       
Rash generalised * 1  0/642 (0.00%)  0 0/209 (0.00%)  0 1/216 (0.46%)  1
Vascular disorders       
Thrombosis * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Deep vein thrombosis * 1  1/642 (0.16%)  1 0/209 (0.00%)  0 0/216 (0.00%)  0
Venous insufficiency * 1  0/642 (0.00%)  0 1/209 (0.48%)  1 0/216 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300) Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300) Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   310/642 (48.29%)      116/209 (55.50%)      121/216 (56.02%)    
Gastrointestinal disorders       
Abdominal pain lower * 1  14/642 (2.18%)  14 12/209 (5.74%)  12 5/216 (2.31%)  7
Diarrhoea * 1  60/642 (9.35%)  82 24/209 (11.48%)  31 22/216 (10.19%)  28
Nausea * 1  27/642 (4.21%)  34 11/209 (5.26%)  12 12/216 (5.56%)  18
Vomiting * 1  36/642 (5.61%)  52 12/209 (5.74%)  15 9/216 (4.17%)  12
General disorders       
Fatigue * 1  20/642 (3.12%)  25 7/209 (3.35%)  8 13/216 (6.02%)  15
Influenza like illness * 1  13/642 (2.02%)  19 14/209 (6.70%)  21 18/216 (8.33%)  22
Infections and infestations       
Cystitis * 1  33/642 (5.14%)  46 23/209 (11.00%)  32 14/216 (6.48%)  20
Gastroenteritis * 1  34/642 (5.30%)  38 15/209 (7.18%)  17 13/216 (6.02%)  14
Influenza * 1  23/642 (3.58%)  29 10/209 (4.78%)  13 14/216 (6.48%)  16
Nasopharyngitis * 1  129/642 (20.09%)  213 43/209 (20.57%)  62 53/216 (24.54%)  83
Sinusitis * 1  17/642 (2.65%)  22 13/209 (6.22%)  17 11/216 (5.09%)  12
Vulvovaginal candidiasis * 1  25/642 (3.89%)  36 12/209 (5.74%)  14 12/216 (5.56%)  21
Musculoskeletal and connective tissue disorders       
Back pain * 1  18/642 (2.80%)  19 12/209 (5.74%)  13 13/216 (6.02%)  14
Nervous system disorders       
Headache * 1  88/642 (13.71%)  168 41/209 (19.62%)  62 48/216 (22.22%)  76
Reproductive system and breast disorders       
Dysmenorrhoea * 1  31/642 (4.83%)  41 11/209 (5.26%)  12 15/216 (6.94%)  22
Respiratory, thoracic and mediastinal disorders       
Oropharyngeal pain * 1  16/642 (2.49%)  17 9/209 (4.31%)  12 11/216 (5.09%)  17
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.1
Data for center no. 1148 was included in “all randomized” set of subjects, but not in FAS, as during medical monitoring of laboratory data a suspicion of potential misconduct was found. An audit was made, but the suspicion could not be resolved.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area Head
Organization: BAYER
EMail: clinical-trials-contact@bayerhealthcare.com
Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00266032     History of Changes
Other Study ID Numbers: 91450
2005-002125-32 ( EudraCT Number )
308683 ( Other Identifier: Company Internal )
First Submitted: December 14, 2005
First Posted: December 15, 2005
Results First Submitted: October 28, 2009
Results First Posted: March 3, 2010
Last Update Posted: November 3, 2014