Study on Safety and Efficacy of an Oral Contraceptive in... | NCT00266032

NCT00266032

ID	Type	Description	Link
2005-002125-32	EudraCT Number
308683	Other Identifier	Company Internal

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Flexible (extended) treatment of EE20/DRSP (YAZ, BAY86-5300)	Experimental	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.	Drug: Flexible (extended) treatment of EE20/DRSP (YAZ, BAY86-5300)
Fixed extended treatment of EE20/DRSP (YAZ, BAY86-5300)	Experimental	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.	Drug: Fixed extended treatment of EE20/DRSP (YAZ, BAY86-5300)
Standard 24+4 treatment of EE20/DRSP (YAZ, BAY86-5300)	Active Comparator	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.	Drug: Standard 24+4 treatment of EE20/DRSP (YAZ, BAY86-5300)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Flexible (extended) treatment of EE20/DRSP (YAZ, BAY86-5300)	Drug	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Days With Bleeding Including Spotting	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.	up to 1 year
Number of Unintended Pregnancies in Yaz Flexible Arm	Pregnancies with conception date within 4 days after end of study medication were regarded as during treatment.	up to 2 years
Pearl Index	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.	Up to 2 years
Number of Unintended Pregnancies Due to Method Failure	Not included in this analysis are pregnancies due to subject failure eg. non-compliance with tablet intake rules.	Up to 2 years
Adjusted Pearl Index	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.	Up to 2 years

Secondary Outcomes

Measure	Description	Time Frame
Number of Days With Bleeding Excluding Spotting	The number of bleeding days per volunteer was calculated by summing up all days with bleeding intensity light, normal, or heavy.	up to 1 year
Number of Bleeding Days During One Year of Treatment in Subjects With at Least 248 Days of Exposure Normalized to 372 Days

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Bayer Study Director	Bayer	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
22454004	Result	Klipping C, Duijkers I, Fortier MP, Marr J, Trummer D, Elliesen J. Long-term tolerability of ethinylestradiol 20 mug/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study. J Fam Plann Reprod Health Care. 2012 Apr;38(2):84-93. doi: 10.1136/jfprhc-2011-100214.
22454003	Result

Label	URL
Click here to find information about studies related to Bayer Healthcare products conducted in Europe	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

Masking Info

FG000691 subjectsall randomized subjects, baseline data for full analysis set (FAS) only

FG001236 subjectsall randomized subjects, baseline data for full analysis set (FAS) only

FG002239 subjectsall randomized subjects, baseline data for full analysis set (FAS) only

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

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

Mean

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00024.8(18 to 35) BG00124.8(18 to 35) BG00224.3(18 to 35) BG003

Sex: Female, Male

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

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000642 BG001209 BG002

Body-Mass-Index (BMI)

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).

Mean

Full Range

kg/m²

Title

Denominators

Categories

Title	Measurements
	BG00022.541(17.95 to 30.50) BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Days With Bleeding Including Spotting

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.

Full Analysis Set (FAS) (reflecting Intention To Treat (ITT) population), all treated subjects with data available, no imputation

Posted

Mean

Standard Deviation

days

up to 1 year

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Units	Counts
Participants	OG000640 OG001209 OG002215

Title

Denominators

Categories

Title	Measurements
	OG00041± 29 OG00161± 51 OG00266± 27

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002	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.	t-test, 2 sided		<0.0001		Mean Difference (Final Values)	-25	Standard Deviation	29		95	-29	-20			Mean of Yaz flexible regimen minus mean of Yaz standard was tested	No	Superiority or Other

Primary

Number of Unintended Pregnancies in Yaz Flexible Arm

Pregnancies with conception date within 4 days after end of study medication were regarded as during treatment.

Full Analysis Set (reflecting ITT population), all treated subjects, no imputation, including switchers to flexible treatment in second year

Posted

Number

pregnancies

up to 2 years

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Primary

Pearl Index

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.

Full Analysis Set (reflecting ITT population), all treated subjects, no imputation, including switchers to flexible treatment in second year

Posted

Mean

95% Confidence Interval

Pregnancies per 100 woman years

Up to 2 years

ID	Title	Description
OG000	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.

Units	Counts

Primary

Number of Unintended Pregnancies Due to Method Failure

Not included in this analysis are pregnancies due to subject failure eg. non-compliance with tablet intake rules.

Full Analysis Set (reflecting ITT population), all treated subjects, no imputation, including switchers to flexible treatment in second year

Posted

Number

Pregnancies

Up to 2 years

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Primary

Adjusted Pearl Index

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.

Full Analysis Set (reflecting ITT population), all treated subjects, no imputation, including switchers to flexible treatment in second year

Posted

Mean

95% Confidence Interval

Pregnancies per 100 woman years

Up to 2 years

ID	Title	Description
OG000	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.

Units	Counts
Participants

Secondary

Number of Days With Bleeding Excluding Spotting

The number of bleeding days per volunteer was calculated by summing up all days with bleeding intensity light, normal, or heavy.

FAS

Posted

Mean

Standard Deviation

Days

up to 1 year

ID	Title	Description
OG000	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.
OG001	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.
OG002

Secondary

Number of Bleeding Days During One Year of Treatment in Subjects With at Least 248 Days of Exposure Normalized to 372 Days

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.

FAS (reflecting ITT population), all treated subjects, no imputation

Posted

Mean

Standard Deviation

Days

up to 1 year

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Number of Bleeding / Spotting Days by 90-day Reference Period

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.

FAS (reflecting ITT), all treated subjects, no imputation

Posted

Mean

Standard Deviation

Days

up to 1 year

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Number of Bleeding / Spotting Episodes in 90 Day Reference Period

The mean number of bleeding / spotting episodes was analyzed using reference periods of 90 days as recommended by the WHO.

FAS (reflecting ITT), all treated subjects, no imputation

Posted

Mean

Standard Deviation

Episodes

Up to one year

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Days With Scheduled Versus Unscheduled Bleeding

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.

FAS (reflecting ITT), all treated subjects, no imputation

Posted

Mean

Standard Deviation

Days

Up to one year

ID	Title	Description
OG000	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.
OG001	Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)

Post-Hoc

Number of Unintended Pregnancies Including Pregnancies Occuring Within 14 Days After End of Study Medication.

Pregnancies with conception date during treatment and within 14 days after end of study medication were included.

FAS

Posted

Number

Pregnancies

Up to one year

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Post-Hoc

Pearl Index (FDA Criteria)

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.

FAS

Posted

Mean

95% Confidence Interval

Pregnancies per 100 woman years

Up to one year

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	19	642	310	642
EG001	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.	7	209	116	209
EG002	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.	3	216	121	216

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 11.1	Non-systematic Assessment	EG0002 events2 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Asthenia	General disorders	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Appendicitis	Infections and infestations	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Gastroenteritis	Infections and infestations	MedDRA 11.1	Non-systematic Assessment	EG0000 events0 affected642 at risk EG0011 events1 affected209 at risk EG0020 events0 affected216 at risk
Pyelonephritis	Infections and infestations	MedDRA 11.1	Non-systematic Assessment	EG0000 events0 affected642 at risk EG0011 events1 affected209 at risk EG0020 events0 affected216 at risk
Tonsillitis	Infections and infestations	MedDRA 11.1	Non-systematic Assessment	EG0000 events0 affected642 at risk EG0011 events1 affected209 at risk EG0020 events0 affected216 at risk
Urinary tract infection	Infections and infestations	MedDRA 11.1	Non-systematic Assessment	EG0000 events0 affected642 at risk EG0011 events1 affected209 at risk EG0020 events0 affected216 at risk
Vulval abscess	Infections and infestations	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Perineal abscess	Infections and infestations	MedDRA 11.1	Non-systematic Assessment	EG0000 events0 affected642 at risk EG0011 events1 affected209 at risk EG0020 events0 affected216 at risk
Gynaecological chlamydia infection	Infections and infestations	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Concussion	Injury, poisoning and procedural complications	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 11.1	Non-systematic Assessment	EG0000 events0 affected642 at risk EG0011 events1 affected209 at risk EG0020 events0 affected216 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 11.1	Non-systematic Assessment	EG0000 events0 affected642 at risk EG0011 events1 affected209 at risk EG0020 events0 affected216 at risk
Postoperative thrombosis	Injury, poisoning and procedural complications	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Ligament rupture	Injury, poisoning and procedural complications	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 11.1	Non-systematic Assessment	EG0000 events0 affected642 at risk EG0010 events0 affected209 at risk EG0021 events1 affected216 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Focal nodular hyperplasia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Cervix carcinoma stage 0	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 11.1	Non-systematic Assessment	EG0000 events0 affected642 at risk EG0010 events0 affected209 at risk EG0021 events1 affected216 at risk
Loss of consciousness	Nervous system disorders	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Calculus urinary	Renal and urinary disorders	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Renal colic	Renal and urinary disorders	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0011 events1 affected209 at risk EG0020 events0 affected216 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Pelvic peritoneal adhesions	Reproductive system and breast disorders	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Nasal polyps	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA 11.1	Non-systematic Assessment	EG0000 events0 affected642 at risk EG0010 events0 affected209 at risk EG0021 events1 affected216 at risk
Thrombosis	Vascular disorders	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 11.1	Non-systematic Assessment	EG0001 events1 affected642 at risk EG0010 events0 affected209 at risk EG0020 events0 affected216 at risk
Venous insufficiency	Vascular disorders	MedDRA 11.1	Non-systematic Assessment	EG0000 events0 affected642 at risk EG0011 events1 affected209 at risk EG0020 events0 affected216 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain lower	Gastrointestinal disorders	MedDRA 11.1	Non-systematic Assessment	EG00014 events14 affected642 at risk EG00112 events12 affected209 at risk EG0027 events5 affected216 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 11.1	Non-systematic Assessment	EG00082 events60 affected642 at risk EG00131 events24 affected209 at risk EG00228 events22 affected216 at risk
Nausea	Gastrointestinal disorders	MedDRA 11.1	Non-systematic Assessment	EG00034 events27 affected642 at risk EG00112 events11 affected209 at risk EG00218 events12 affected216 at risk
Vomiting	Gastrointestinal disorders	MedDRA 11.1	Non-systematic Assessment	EG00052 events36 affected642 at risk EG00115 events12 affected209 at risk EG00212 events9 affected216 at risk
Fatigue	General disorders	MedDRA 11.1	Non-systematic Assessment	EG00025 events20 affected642 at risk EG0018 events7 affected209 at risk EG00215 events13 affected216 at risk
Influenza like illness	General disorders	MedDRA 11.1	Non-systematic Assessment	EG00019 events13 affected642 at risk EG00121 events14 affected209 at risk EG00222 events18 affected216 at risk
Cystitis	Infections and infestations	MedDRA 11.1	Non-systematic Assessment	EG00046 events33 affected642 at risk EG00132 events23 affected209 at risk EG00220 events14 affected216 at risk
Gastroenteritis	Infections and infestations	MedDRA 11.1	Non-systematic Assessment	EG00038 events34 affected642 at risk EG00117 events15 affected209 at risk EG00214 events13 affected216 at risk
Influenza	Infections and infestations	MedDRA 11.1	Non-systematic Assessment	EG00029 events23 affected642 at risk EG00113 events10 affected209 at risk EG00216 events14 affected216 at risk
Nasopharyngitis	Infections and infestations	MedDRA 11.1	Non-systematic Assessment	EG000213 events129 affected642 at risk EG00162 events43 affected209 at risk EG00283 events53 affected216 at risk
Sinusitis	Infections and infestations	MedDRA 11.1	Non-systematic Assessment	EG00022 events17 affected642 at risk EG00117 events13 affected209 at risk EG00212 events11 affected216 at risk
Vulvovaginal candidiasis	Infections and infestations	MedDRA 11.1	Non-systematic Assessment	EG00036 events25 affected642 at risk EG00114 events12 affected209 at risk EG00221 events12 affected216 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 11.1	Non-systematic Assessment	EG00019 events18 affected642 at risk EG00113 events12 affected209 at risk EG00214 events13 affected216 at risk
Headache	Nervous system disorders	MedDRA 11.1	Non-systematic Assessment	EG000168 events88 affected642 at risk EG00162 events41 affected209 at risk EG00276 events48 affected216 at risk
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA 11.1	Non-systematic Assessment	EG00041 events31 affected642 at risk EG00112 events11 affected209 at risk EG00222 events15 affected216 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Non-systematic Assessment	EG00017 events16 affected642 at risk EG00112 events9 affected209 at risk EG00217 events11 affected216 at risk

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

ID	Term
C534342	drospirenone and ethinyl estradiol combination

BG00222.566(17.90 to 29.80)

BG00322.546(17.90 to 30.50)

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.

Facility	Status	City	State	ZIP	Country	Contacts
		Drummondville	Quebec	J2B 1H8	Canada