SH T00186 Phase II/ III Optimal Drospirenone (DRSP) Dose Finding and Placebo-controlled Comparative Study

This study has been completed.

Sponsor:

Information provided by:

Bayer

ClinicalTrials.gov Identifier:

NCT00511797

First received: August 3, 2007

Last updated: December 26, 2012

Last verified: December 2012

History of Changes

Results First Received: April 15, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double-Blind; Primary Purpose: Treatment
Condition:	Dysmenorrhea
Interventions:	Drug: SH T04740B Drug: SH T00186DF Drug: SH T04740F Drug: Placebo

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Full Analysis Set (FAS) consisted of all patients who received at least one dose of study drug. Patients were analyzed as treated. FAS was the primary analysis set for all efficacy endpoints and safety analyses. Per Protocol Set (PPS) was a subgroup of the FAS. The PPS consisted of patients in the FAS who did not have major protocol deviations.

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Full Analysis Set (FAS) consisted of all patients who received at least one dose of study drug. Patients were analyzed as treated.

FAS was the primary analysis set for all efficacy endpoints and safety analyses. Per Protocol Set (PPS) was a subgroup of the FAS. The PPS consisted of patients in the FAS who did not have major protocol deviations.

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Participant Flow: Overall Study

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
STARTED	62	63	62	62
Subjects Dispensed Drugs	61	63	61	59
Subjects Received Treatment	61 ^[1]	62 ^[1]	61 ^[1]	58 ^[1]
COMPLETED	55	55	51	47
NOT COMPLETED	7	8	11	15
Adverse Event	1	2	2	2
Lost to Follow-up	1	0	0	1
Pregnancy	0	0	0	1
Protocol Violation	0	2	2	3
Withdrawal by Subject	3	3	4	2
Never dispensed	1	0	1	3
Study drug not taken	0	1	0	1
Partially missing diary	0	0	1	0
Other (moving etc)	1	0	1	2

[1]	FAS

Baseline Characteristics

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Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle
Total	Total of all reporting groups

Baseline Measures

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo	Total
Number of Participants [units: participants]	61	62	61	58	242
Age [units: years] Mean ( Full Range )	31.0 ( 21 to 45 )	30.6 ( 20 to 43 )	30.9 ( 20 to 48 )	30.8 ( 20 to 44 )	30.8 ( 20 to 48 )
Gender [units: participants]
Female	61	62	61	58	242
Male	0	0	0	0	0
Diagnosis type [units: participants]
Functional dysmenorrhea	47	48	42	41	178
Organic dysmenorrhea	14	14	19	17	64
Details of organic dysmenorrhea ^[1] [units: participants]
Endometriosis	1	3	4	5	13
Uterine fibroids	9	7	10	9	35
Uterine adenomyosis	6	7	11	8	32
Bicornuate uterus	2	0	0	0	2
Average length of menstrual cycle [units: days] Mean ( Full Range )	28.6 ( 25 to 31 )	28.7 ( 25 to 33 )	28.3 ( 25 to 32 )	28.7 ( 25 to 31 )	28.6 ( 25 to 33 )
Body mass index (BMI) [units: kg/m^2] Mean ( Full Range )	21.05 ( 15.6 to 30.0 )	20.41 ( 16.6 to 25.8 )	20.67 ( 16.4 to 29.9 )	21.19 ( 17.2 to 27.7 )	20.82 ( 15.6 to 30.0 )

[1]	Not all participants had organic dysmenorrhea. Some of participants were diagnosed as having a multiple type of organic dysmenorrhea.

Outcome Measures

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1. Primary:

Change From Baseline in Total Dysmenorrheal Score at Final Evaluation [ Time Frame: Baseline and up to 4 Cycles (28 days per cycle) ]

Measure Type	Primary
Measure Title	Change From Baseline in Total Dysmenorrheal Score at Final Evaluation
Measure Description	Total dysmenorrheal score was defined as sum of 2 sub-scores: severity of dysmenorrhea (none: 0, mild: 1, moderate: 2, severe: 3) and use of analgesics (none: 0, mild: 1, moderate: 2, severe: 3). Total possible best is 0, and total possible worst is 6. Note: used with permission of Nobelpharma Co., Ltd. from the phase 3 clinical study protocol (Prog Med 2005:25 (3):739-758) of IKH-01 in dysmenorrhea (associated with endometriosis) (Nobelpharma Co., Ltd.)
Time Frame	Baseline and up to 4 Cycles (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	61	62	61	58
Change From Baseline in Total Dysmenorrheal Score at Final Evaluation [units: scores on a scale] Mean ± Standard Deviation	-2.5 ± 1.52	-2.1 ± 1.51	-1.9 ± 1.63	-1.0 ± 1.53

Statistical Analysis 1 for Change From Baseline in Total Dysmenorrheal Score at Final Evaluation

Groups ^[1]	DRSP 3 mg/EE 20 μg vs. Placebo
Method ^[2]	t-test, 1 sided
P Value ^[3]	<0.001
Median Difference (Final Values) ^[4]	-0.92
Standard Error of the mean	± 0.290
95% Confidence Interval	( -1.49 to -0.34 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Three null hypotheses were sequentially tested. H01: DRSP 3 mg >= Placebo (Active is equal or less in decrease of score) vs H11: DRSP 3 mg < Placebo (Active is greater in decrease of score), H02: DRSP 2 mg >= Placebo vs H12: DRSP 2 mg < Placebo, H03: DRSP 1 mg >= Placebo vs H13: DRSP 1 mg < Placebo.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Pre-defined sequential tests were applied to protect alpha inflation by multiplicity.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change From Baseline in Total Dysmenorrheal Score at Final Evaluation

Groups ^[1]	DRSP 2 mg/EE 20 μg vs. Placebo
Method ^[2]	t-test, 1 sided
P Value ^[3]	<0.001
Median Difference (Final Values) ^[4]	-1.10
Standard Error of the mean	± 0.277
95% Confidence Interval	( -1.64 to -0.55 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Second null hypothesis was tested. H02: DRSP 2 mg >= Placebo vs H12: DRSP 2 mg < Placebo.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Change From Baseline in Total Dysmenorrheal Score at Final Evaluation

Groups ^[1]	DRSP 1 mg/EE 20 μg vs. Placebo
Method ^[2]	t-test, 1 sided
P Value ^[3]	<0.001
Median Difference (Final Values) ^[4]	-1.44
Standard Error of the mean	± 0.280
95% Confidence Interval	( -2.00 to -0.89 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Third null hypotheses was tested. H03: DRSP 1 mg >= Placebo vs H13: DRSP 1 mg < Placebo.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

2. Secondary:

Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 [ Time Frame: Baseline and up to 4 Cycles (28 days per cycle) ]

Measure Type	Secondary
Measure Title	Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4
Measure Description	Total dysmenorrheal score was defined as sum of 2 sub-scores: severity of dysmenorrhea (none: 0, mild: 1, moderate: 2, severe: 3) and use of analgesics (none: 0, mild: 1, moderate: 2, severe: 3). Total possible best is 0, and total possible worst is 6.
Time Frame	Baseline and up to 4 Cycles (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	61	62	61	58
Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 [units: scores on a scale] Mean ± Standard Deviation
Cycle 1	-2.4 ± 1.40	-2.1 ± 1.49	-1.8 ± 1.67	-0.8 ± 1.50
Cycle 2	-2.1 ± 1.40	-2.3 ± 1.57	-1.9 ± 1.50	-1.1 ± 1.59
Cycle 3	-2.5 ± 1.34	-2.3 ± 1.52	-2.1 ± 1.34	-1.0 ± 1.59
Cycle 4	-2.5 ± 1.55	-2.3 ± 1.41	-2.1 ± 1.54	-1.0 ± 1.63

Statistical Analysis 1 for Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4

Groups ^[1]	DRSP 3 mg/EE 20 μg vs. Placebo
Method ^[2]	t-test, 1 sided
P Value ^[3]	<0.001
Mean Difference (Final Values) ^[4]	-1.10
Standard Error of the mean	± 0.322
95% Confidence Interval	( -1.74 to -0.46 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Test results of 3 mg DRSP and placebo at Cycle 4 are shown. 2-sided 95% confidence intervals were calculated. To keep consistency with 2-sided 95% confidence intervals, 2.5% 1-sided significance levels were used for the statistical tests.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4

Groups ^[1]	DRSP 2 mg/EE 20 μg vs. Placebo
Method ^[2]	t-test, 1 sided
P Value ^[3]	<0.001
Mean Difference (Final Values) ^[4]	-1.34
Standard Error of the mean	± 0.306
95% Confidence Interval	( -1.95 to -0.73 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4

Groups ^[1]	DRSP 1 mg/EE 20 μg vs. Placebo
Method ^[2]	t-test, 1 sided
P Value ^[3]	<0.001
Mean Difference (Final Values) ^[4]	-1.53
Standard Error of the mean	± 0.317
95% Confidence Interval	( -2.16 to -0.90 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

3. Secondary:

Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 [ Time Frame: Cycle 4 (28 days per cycle) ]

Measure Type	Secondary
Measure Title	Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4
Measure Description	Severity of lower abdominal pain during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).
Time Frame	Cycle 4 (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with data at Cycle 4)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	55	53	51	46
Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 [units: participants]
none	15	17	11	3
mild	28	27	19	11
moderate	9	7	14	21
severe	3	2	7	11

No statistical analysis provided for Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4

4. Secondary:

Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 [ Time Frame: Cycle 4 (28 days per cycle) ]

Measure Type	Secondary
Measure Title	Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4
Measure Description	Severity of low back pain during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).
Time Frame	Cycle 4 (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with data at Cycle 4)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	55	53	51	46
Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 [units: participants]
none	34	36	30	18
mild	15	12	18	14
moderate	5	4	2	9
severe	1	1	1	5

No statistical analysis provided for Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4

5. Secondary:

Number of Participants With Severity of Headache During Menstruation at Cycle 4 [ Time Frame: Cycle 4 (28 days per cycle) ]

Measure Type	Secondary
Measure Title	Number of Participants With Severity of Headache During Menstruation at Cycle 4
Measure Description	Severity of headache during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).
Time Frame	Cycle 4 (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with data at Cycle 4)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	55	53	51	46
Number of Participants With Severity of Headache During Menstruation at Cycle 4 [units: participants]
none	47	35	39	29
mild	5	10	5	6
moderate	1	6	3	6
severe	2	2	4	5

No statistical analysis provided for Number of Participants With Severity of Headache During Menstruation at Cycle 4

6. Secondary:

Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 [ Time Frame: Cycle 4 (28 days per cycle) ]

Measure Type	Secondary
Measure Title	Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4
Measure Description	Severity of nausea or vomiting during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).
Time Frame	Cycle 4 (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with data at Cycle 4)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	55	53	51	46
Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 [units: participants]
none	51	47	47	40
mild	2	4	4	4
moderate	2	1	0	2
severe	0	1	0	0

No statistical analysis provided for Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4

7. Secondary:

Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 [ Time Frame: Cycle 4 (28 days per cycle) ]

Measure Type	Secondary
Measure Title	Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4
Measure Description	Total pelvic pain score was defined as sum of 2 sub-scores: severity of dysmenorrhea and use of analgesics. Higher score means it is more severe. 0=None, 6=Severest.
Time Frame	Cycle 4 (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with data at Cycle 4)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	55	53	51	46
Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 [units: participants]
0	40	41	42	30
1	11	10	7	6
2	3	2	1	5
3	0	0	0	3
4	0	0	0	1
5	1	0	1	1
6	0	0	0	0

No statistical analysis provided for Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4

8. Secondary:

Change From Baseline in Visual Analogue Scale (VAS) for Dysmenorrhea at Times Other Than During Menstruation at Cycle 4 [ Time Frame: From baseline up to Cycle 4 (28 days per cycle) ]

Measure Type	Secondary
Measure Title	Change From Baseline in Visual Analogue Scale (VAS) for Dysmenorrhea at Times Other Than During Menstruation at Cycle 4
Measure Description	VAS is an unmarked scale on a line 100 mm in length, indicating from 0 mm (no pain) to 100 mm (worst pain a participant has ever experienced).
Time Frame	From baseline up to Cycle 4 (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with data at Cycle 4)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	55	53	51	46
Change From Baseline in Visual Analogue Scale (VAS) for Dysmenorrhea at Times Other Than During Menstruation at Cycle 4 [units: scores on a scale] Mean ± Standard Deviation	-43.0 ± 23.44	-39.5 ± 22.12	-31.8 ± 23.55	-10.3 ± 24.53

No statistical analysis provided for Change From Baseline in Visual Analogue Scale (VAS) for Dysmenorrhea at Times Other Than During Menstruation at Cycle 4

9. Secondary:

Visual Analogue Scale (VAS) for Pelvic Pain at Times Other Than During Menstruation at Cycle 4 [ Time Frame: Cycle 4 (28 days per cycle) ]

Measure Type	Secondary
Measure Title	Visual Analogue Scale (VAS) for Pelvic Pain at Times Other Than During Menstruation at Cycle 4
Measure Description	VAS is an unmarked scale on a line 100 mm in length, indicating from 0 mm (no pain) to 100 mm (worst pain a participant has ever experienced).
Time Frame	Cycle 4 (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with data at Cycle 4)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	55	53	51	46
Visual Analogue Scale (VAS) for Pelvic Pain at Times Other Than During Menstruation at Cycle 4 [units: scores on a scale] Mean ± Standard Deviation	5.9 ± 11.52	5.4 ± 11.78	4.0 ± 14.26	11.5 ± 20.22

No statistical analysis provided for Visual Analogue Scale (VAS) for Pelvic Pain at Times Other Than During Menstruation at Cycle 4

10. Secondary:

Change From Baseline in Endometrial Thickness After 4-cycle Treatment [ Time Frame: From baseline to Cycle 4 (28 days per cycle) ]

Measure Type	Secondary
Measure Title	Change From Baseline in Endometrial Thickness After 4-cycle Treatment
Measure Description	Endometrial thickness was measured via transvaginal ultrasound examination. The endometrium is the inner membrane of the uterus. During the menstrual cycle, the endometrium grows to a thick, blood vessel-rich, glandular tissue layer.
Time Frame	From baseline to Cycle 4 (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with data at Cycle 4)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	53	53	50	47
Change From Baseline in Endometrial Thickness After 4-cycle Treatment [units: mm] Mean ± Standard Deviation	-5.5 ± 4.11	-7.1 ± 3.25	-6.3 ± 4.07	-0.1 ± 2.79

No statistical analysis provided for Change From Baseline in Endometrial Thickness After 4-cycle Treatment

11. Secondary:

Number of Bleeding / Spotting Episodes [ Time Frame: For the first 90 days ]

Measure Type	Secondary
Measure Title	Number of Bleeding / Spotting Episodes
Measure Description	Bleeding data were captured from the diary a participant recorded by herself. Bleeding is a genital bleeding. Spotting is a slight genital bleeding with participant's experience. An episode means a series of bleeding and/or spotting. The bleeding /spotting analyses are by intensity.
Time Frame	For the first 90 days
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with the defined data)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	59	60	57	56
Number of Bleeding / Spotting Episodes [units: number of episodes] Mean ± Standard Deviation
bleeding / spotting	3.3 ± 0.9	3.3 ± 1.3	3.4 ± 0.9	2.9 ± 0.9
bleeding only	0.5 ± 0.9	0.4 ± 0.8	0.3 ± 0.5	0.4 ± 0.8
spotting only	0.3 ± 0.6	0.4 ± 1.1	0.4 ± 0.8	0.2 ± 0.6

No statistical analysis provided for Number of Bleeding / Spotting Episodes

12. Secondary:

Number of Bleeding / Spotting Days [ Time Frame: For the first 90 days ]

Measure Type	Secondary
Measure Title	Number of Bleeding / Spotting Days
Measure Description	Bleeding data were captured from the diary a participant recorded by herself. Bleeding is a genital bleeding. Spotting is a slight genital bleeding with participant's experience. The bleeding /spotting analyses are by intensity.
Time Frame	For the first 90 days
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with the defined data)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	59	60	57	56
Number of Bleeding / Spotting Days [units: days] Mean ± Standard Deviation
bleeding / spotting	32.3 ± 8.7	31.2 ± 11.4	29.2 ± 11.0	22.6 ± 5.5
bleeding only	21.3 ± 5.9	19.3 ± 8.8	18.6 ± 6.5	17.4 ± 4.9
spotting only	11.1 ± 7.0	11.9 ± 7.6	10.5 ± 8.2	5.2 ± 2.5

No statistical analysis provided for Number of Bleeding / Spotting Days

13. Secondary:

Participants With Withdrawal Bleeding [ Time Frame: At Cycle 4 (28 days per cycle) ]

Measure Type	Secondary
Measure Title	Participants With Withdrawal Bleeding
Measure Description	Withdrawal bleedings were defined as bleedings while a participant takes placebo tablets.
Time Frame	At Cycle 4 (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with data at Cycle 4)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	55	55	52	48
Participants With Withdrawal Bleeding [units: participants]	50	50	49	47

No statistical analysis provided for Participants With Withdrawal Bleeding

14. Secondary:

Participants With Intracyclic Bleeding [ Time Frame: At Cycle 4 (28 days per cycle) ]

Measure Type	Secondary
Measure Title	Participants With Intracyclic Bleeding
Measure Description	Intracyclic bleedings were defined as bleedings while a participant takes active drugs.
Time Frame	At Cycle 4 (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with data at Cycle 4)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	55	55	52	48
Participants With Intracyclic Bleeding [units: participants]	14	8	8	4

No statistical analysis provided for Participants With Intracyclic Bleeding

15. Secondary:

Participants With Non-heavy Intracyclic Bleeding [ Time Frame: At Cycle 4 (28 days per cycle) ]

Measure Type	Secondary
Measure Title	Participants With Non-heavy Intracyclic Bleeding
Measure Description	Non-heavy bleedings were defined as those other than heavy bleeding (less or normal bleeding).
Time Frame	At Cycle 4 (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with data at Cycle 4)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	14	8	8	4
Participants With Non-heavy Intracyclic Bleeding [units: participants]	14	8	7	2

No statistical analysis provided for Participants With Non-heavy Intracyclic Bleeding

16. Secondary:

Participants With Non-heavy Withdrawal Bleeding [ Time Frame: At Cycle 4 (28 dyas per cycle) ]

Measure Type	Secondary
Measure Title	Participants With Non-heavy Withdrawal Bleeding
Measure Description	Non-heavy bleedings were defined as those other than heavy bleeding (less or normal bleeding).
Time Frame	At Cycle 4 (28 dyas per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with data at Cycle 4)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	50	50	49	47
Participants With Non-heavy Withdrawal Bleeding [units: participants]	45	44	42	38

No statistical analysis provided for Participants With Non-heavy Withdrawal Bleeding

17. Secondary:

Change From Baseline in Serum Carbohydrate Antigen-125 (CA125) After 4-cycle Treatment [ Time Frame: From baseline to Cycle 4 (28 days per cycle) ]

Measure Type	Secondary
Measure Title	Change From Baseline in Serum Carbohydrate Antigen-125 (CA125) After 4-cycle Treatment
Measure Description	CA125 is a laboratory parameter giving an indication of having tumor, whose elevated levels that were defined by a lab suggest a potential tumor.
Time Frame	From baseline to Cycle 4 (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with data at Cycle 4)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	55	55	51	47
Change From Baseline in Serum Carbohydrate Antigen-125 (CA125) After 4-cycle Treatment [units: Units/L] Mean ( Full Range )	-2.78 ( -26.4 to 5.5 )	0.53 ( -17.4 to 184.9 )	-3.79 ( -35.6 to 32.5 )	0.89 ( -7.8 to 15.8 )

No statistical analysis provided for Change From Baseline in Serum Carbohydrate Antigen-125 (CA125) After 4-cycle Treatment

18. Secondary:

Change From Baseline in Serum C-reactive Protein (CRP) After 4-cycle Treatment [ Time Frame: From baseline to Cycle 4 (28 days per cycle) ]

Measure Type	Secondary
Measure Title	Change From Baseline in Serum C-reactive Protein (CRP) After 4-cycle Treatment
Measure Description	CRP is a laboratory parameter giving an indication of inflammation, whose elevated levels that were defined by a lab suggest a potential inflammation.
Time Frame	From baseline to Cycle 4 (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with data at Cycle 4)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	55	55	51	47
Change From Baseline in Serum C-reactive Protein (CRP) After 4-cycle Treatment [units: mg/dL] Mean ( Full Range )	0.015 ( -0.31 to 0.85 )	0.042 ( -0.09 to 0.77 )	-0.014 ( -2.73 to 0.35 )	-0.175 ( -7.38 to 0.62 )

No statistical analysis provided for Change From Baseline in Serum C-reactive Protein (CRP) After 4-cycle Treatment

19. Secondary:

Change From Baseline in Serum Estradiol Level After 4-cycle Treatment [ Time Frame: From baseline to Cycle 4 (28 days per cycle) ]

Measure Type	Secondary
Measure Title	Change From Baseline in Serum Estradiol Level After 4-cycle Treatment
Measure Description	Estradiol is a predominant sex hormone that presents in female.
Time Frame	From baseline to Cycle 4 (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with data at Cycle 4)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	55	55	51	48
Change From Baseline in Serum Estradiol Level After 4-cycle Treatment [units: pg/mL] Mean ( Full Range )	-18.32 ( -341.5 to 968.9 )	-42.23 ( -336.8 to 329.0 )	-98.02 ( -477.8 to 231.2 )	49.20 ( -182.7 to 310.3 )

No statistical analysis provided for Change From Baseline in Serum Estradiol Level After 4-cycle Treatment

20. Secondary:

Change From Baseline in Serum Progesterone Level at Cycle 4 [ Time Frame: From baseline to Cycle 4 (28 days per cycle) ]

Measure Type	Secondary
Measure Title	Change From Baseline in Serum Progesterone Level at Cycle 4
Measure Description	Progesterone is a steroid hormone involving in the female menstrual cycle, pregnancy, etc.
Time Frame	From baseline to Cycle 4 (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with data at Cycle 4)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	54	53	50	47
Change From Baseline in Serum Progesterone Level at Cycle 4 [units: ng/mL] Mean ( Full Range )	-7.93 ( -22.2 to 6.3 )	-8.23 ( -23.6 to 5.7 )	-9.37 ( -22.3 to 6.7 )	-0.27 ( -20.6 to 18.7 )

No statistical analysis provided for Change From Baseline in Serum Progesterone Level at Cycle 4

21. Post-Hoc:

Change From Baseline for Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 [ Time Frame: From baseline to Cycle 4(28 days per cycle) ]

Measure Type	Post-Hoc
Measure Title	Change From Baseline for Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4
Measure Description	Total pelvic pain score was defined as sum of 2 sub-scores: severity of dysmenorrhea (none: 0, mild: 1, moderate: 2, severe: 3) and use of analgesics (none: 0, mild: 1, moderate: 2, severe: 3). Total possible best is 0, and total possible worst is 6.
Time Frame	From baseline to Cycle 4(28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (Participants with data at Cycle 4)

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	55	53	51	46
Change From Baseline for Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 [units: scores on a scale] Mean ± Standard Deviation	-0.1 ± 1.19	-0.3 ± 1.12	-0.1 ± 1.06	0.1 ± 1.22

No statistical analysis provided for Change From Baseline for Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4

22. Post-Hoc:

Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) [ Time Frame: Baseline and up to Cycle 4 (28 days per cycle) ]

Measure Type	Post-Hoc
Measure Title	Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1)
Measure Description	Total dysmenorrheal score was defined as sum of 2 sub-scores: severity of dysmenorrhea (none: 0, mild: 1, moderate: 2, severe: 3) and use of analgesics (none: 0, mild: 1, moderate: 2, severe: 3). Total possible best is 0, and total possible worst is 6. Note: used with permission of Nobelpharma Co., Ltd. from the phase 3 clinical study protocol (Prog Med 2005:25 (3):739-758) of IKH-01 in dysmenorrhea (associated with endometriosis) (Nobelpharma Co., Ltd.)
Time Frame	Baseline and up to Cycle 4 (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	61	62	61	58
Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) [units: scores on a scale] Mean ± Standard Deviation
age: < 30 years	-2.2 ± 1.46	-2.4 ± 1.50	-1.9 ± 1.49	-1.2 ± 1.45
age: >= 30 years	-2.8 ± 1.54	-1.9 ± 1.49	-1.9 ± 1.75	-0.8 ± 1.60
weight: < 50 kg	-3.0 ± 1.30	-2.4 ± 0.99	-1.5 ± 1.39	-0.7 ± 1.65
weight: >= 50kg	-2.1 ± 1.57	-2.0 ± 1.64	-2.2 ± 1.74	-1.1 ± 1.50
functional dysmenorrhea	-2.3 ± 1.63	-2.1 ± 1.52	-1.8 ± 1.73	-1.0 ± 1.47
organic dysmenorrhea	-2.9 ± 1.00	-2.1 ± 1.49	-2.3 ± 1.37	-1.0 ± 1.70
with medical surgical history	-2.3 ± 1.62	-2.0 ± 1.50	-2.1 ± 1.61	-1.1 ± 1.68
without medical surgical history	-2.6 ± 1.42	-2.3 ± 1.53	-1.8 ± 1.66	-0.8 ± 1.27

No statistical analysis provided for Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1)

23. Post-Hoc:

Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) [ Time Frame: Baseline and up to 4 Cycles (28 days per cycle) ]

Measure Type	Post-Hoc
Measure Title	Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2)
Measure Description	Total dysmenorrheal score was defined as sum of 2 sub-scores: severity of dysmenorrhea (none: 0, mild: 1, moderate: 2, severe: 3) and use of analgesics (none: 0, mild: 1, moderate: 2, severe: 3). Total possible best is 0, and total possible worst is 6. Note: used with permission of Nobelpharma Co., Ltd. from the phase 3 clinical study protocol (Prog Med 2005:25 (3):739-758) of IKH-01 in dysmenorrhea (associated with endometriosis) (Nobelpharma Co., Ltd.)
Time Frame	Baseline and up to 4 Cycles (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	61	62	61	58
Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) [units: scores on a scale] Mean ± Standard Deviation
with previous medication	-2.5 ± 1.53	-2.1 ± 1.51	-1.9 ± 1.63	-1.0 ± 1.53
with pregnancy history	-2.7 ± 1.62	-1.9 ± 1.32	-2.2 ± 1.72	-1.0 ± 2.03
without pregnancy history	-2.3 ± 1.47	-2.2 ± 1.62	-1.8 ± 1.61	-1.0 ± 1.22
with birth history	-2.9 ± 1.59	-2.1 ± 1.28	-2.3 ± 1.96	-1.1 ± 2.00
without birth history	-2.3 ± 1.49	-2.1 ± 1.62	-1.9 ± 1.55	-1.0 ± 1.35
total dysmenorrheal score at baseline: 3 or 4	-2.1 ± 1.28	-1.9 ± 1.36	-1.8 ± 1.44	-1.0 ± 1.49
total dysmenorrheal score at baseline: 5 or 6	-3.4 ± 1.75	-2.6 ± 1.77	-2.4 ± 2.06	-1.1 ± 1.65

No statistical analysis provided for Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2)

24. Post-Hoc:

Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Patients Without Previous Medication [ Time Frame: Baseline and up to 4 Cycles (28 days per cycle) ]

Measure Type	Post-Hoc
Measure Title	Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Patients Without Previous Medication
Measure Description	Total dysmenorrheal score was defined as sum of 2 sub-scores: severity of dysmenorrhea (none: 0, mild: 1, moderate: 2, severe: 3) and use of analgesics (none: 0, mild: 1, moderate: 2, severe: 3). Total possible best is 0, and total possible worst is 6. Note: used with permission of Nobelpharma Co., Ltd. from the phase 3 clinical study protocol (Prog Med 2005:25 (3):739-758) of IKH-01 in dysmenorrhea (associated with endometriosis) (Nobelpharma Co., Ltd.)
Time Frame	Baseline and up to 4 Cycles (28 days per cycle)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The number of subjects without previous medication in DRSP 1 mg/EE 20 μg group was 1, so the standard deviation was not measurable. The number of subjects without previous medication in the other three groups were 0, so the data were not applicable.

Reporting Groups

	Description
DRSP 1 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 2 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
DRSP 3 mg/EE 20 μg	1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Placebo	1 tablet per day placebo for 28 days in each 28-day cycle

Measured Values

	DRSP 1 mg/EE 20 μg	DRSP 2 mg/EE 20 μg	DRSP 3 mg/EE 20 μg	Placebo
Number of Participants Analyzed [units: participants]	1	0	0	0
Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Patients Without Previous Medication [units: scores on a scale] Mean ± Standard Deviation	-2.0

No statistical analysis provided for Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Patients Without Previous Medication

Serious Adverse Events

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Other Adverse Events

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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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Sponsor will confirm the contents before disclosure.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Therapeutic Area Head
Organization: BAYER
e-mail: clinical-trials-contact@bayerhealthcare.com

No publications provided

Responsible Party:	Therapeutic Area Head, Bayer Yakuhin, Ltd.
ClinicalTrials.gov Identifier:	NCT00511797 History of Changes
Other Study ID Numbers:	91615, 310283
Study First Received:	August 3, 2007
Results First Received:	April 15, 2010
Last Updated:	December 26, 2012
Health Authority:	Japan: Ministry of Health, Labor and Welfare

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