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Clinical Trial Results:
A multi-center, double-blind, double-dummy, randomized, controlled, parallel-group study to assess efficacy and safety of SH T00658ID compared to SH D593B in the treatment of primary dysmenorrhea

Summary
EudraCT number	2008-005625-11
Trial protocol	DE IT
Global end of trial date	18 Nov 2010

Results information
Results version number	v2(current)
This version publication date	02 Sep 2016
First version publication date	26 Jun 2015
Other versions	v1
Version creation reason	New data added to full data set Correction of full data set Bayer sponsor contact information to be updated

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

BAY86-5027/91781

ISRCTN number

US NCT number

NCT00909857

WHO universal trial number (UTN)

Sponsor organisation name

Bayer AG

Sponsor organisation address

Kaiser-Wilhelm-Allee, Leverkusen, Germany, D-51368

Public contact

Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com

Scientific contact

Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

14 Jan 2011

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

18 Nov 2010

Was the trial ended prematurely?

Main objective of the trial

The main objective of the study was to show superiority of SH T00658ID over SH D593B with respect to the number of days with dysmenorrheic pain (defined as pelvic pain during the menstrual/withdrawal bleeding episode and the 2 days before this episode) in a defined period, i.e. comparison between two treatment cycles and two baseline cycles.

Protection of trial subjects

The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Only after the subject voluntarily signed the informed consent form was he/she able to enter the study. If the subject was not capable of providing a signature, an oral statement of consent could have been given in the presence of a witness. Each subject was assured of the right to withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.

Background therapy

Evidence for comparator

Actual start date of recruitment

15 Apr 2009

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 96

Country: Number of subjects enrolled

Italy: 59

Country: Number of subjects enrolled

Chile: 53

Country: Number of subjects enrolled

Canada: 11

Country: Number of subjects enrolled

Philippines: 97

Country: Number of subjects enrolled

Germany: 148

Worldwide total number of subjects

464

EEA total number of subjects

207

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

440

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Subjects aged 14 to 50 years with a need for oral contraception suffering from primary dysmenorrhea were recruited at specialized study sites.

Screening details

Out of 771 subjects screened, 264 failed screening, mostly due to not meeting in-/exclusion criteria (155), withdrawal of consent (49), loss to follow-up (36) or pregnancy (10). Thus, 507 subjects were randomized (253 to Estradiol valerate/Dienogest and 254 to Ethinyl estradiol/Levonorgestrel), out of which 464 subjects received treatment.

Period 1 title

Overall Study

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Carer, Subject, Investigator

Blinding implementation details

For blinding purposes, a double-dummy design was used. The investigational and reference product were packed for a double-dummy design in one wallet with two blisters of 28 tablets each.

Are arms mutually exclusive

Yes

Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)

Arm description

Daily oral administration of one tablet SH T00658ID (BAY86-5027) plus one tablet placebo for 28 days without tablet-free interval for 3 treatment cycles.

Arm type

Experimental

Investigational medicinal product name

Placebo Match to SH T00658ID

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Daily oral administration of one tablet SH T00658ID (BAY86-5027) plus one tablet placebo for 28 days without tablet-free interval for 3 treatment cycles.

Investigational medicinal product name

Estradiol Valerate, Dienogest (SH T00658ID)

Investigational medicinal product code

BAY86-5027

Other name

Natazia, Qlaira

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Daily oral administration of one tablet SH T00658ID (BAY86-5027) plus one tablet placebo for 28 days without tablet-free interval for 3 treatment cycles.

Ethinyl Estradiol, Levonorgestrel (Miranova)

Arm description

Daily oral administration of one tablet placebo plus one tablet SH D593B (Miranova) for 28 days without tablet-free interval for 3 treatment cycles.

Arm type

Active comparator

Investigational medicinal product name

Placebo Match to SH D593B

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Daily oral administration of one tablet placebo plus one tablet SH D593B (Miranova) for 28 days without tablet-free interval for 3 treatment cycles.

Investigational medicinal product name

Ethinyl Estradiol, Levonorgestrel (SH D593B)

Investigational medicinal product code

Other name

Miranova

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Daily oral administration of one tablet placebo plus one tablet SH D593B (Miranova) for 28 days without tablet-free interval for 3 treatment cycles.

Number of subjects in period 1	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Started	253	254
Treated	234	230
Completed	217	209
Not completed	36	45
Consent withdrawn by subject	6	10
Protocol violation	2	1
Pregnancy	1	-
Unknown	1	-
Adverse event	5	5
Lost to follow-up	2	5
Did not receive study medication	19	24

Period 2 title

Baseline period

Is this the baseline period?

Yes ^[1]

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Carer, Subject, Investigator

Are arms mutually exclusive

Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)

Arm description

Daily oral administration of one tablet SH T00658ID (BAY86-5027) plus one tablet placebo for 28 days without tablet-free interval for 3 treatment cycles. Subjects who received treatment were included in baseline period.

Arm type

Experimental

Investigational medicinal product name

Estradiol Valerate, Dienogest (SH T00658ID)

Investigational medicinal product code

BAY86-5027

Other name

Natazia, Qlaira

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Daily oral administration of one tablet SH T00658ID (BAY86-5027) plus one tablet placebo for 28 days without tablet-free interval for 3 treatment cycles.

Investigational medicinal product name

Placebo Match to SH T00658ID

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Daily oral administration of one tablet SH T00658ID (BAY86-5027) plus one tablet placebo for 28 days without tablet-free interval for 3 treatment cycles.

Ethinyl Estradiol, Levonorgestrel (Miranova)

Arm description

Daily oral administration of one tablet placebo plus one tablet SH D593B (Miranova) for 28 days without tablet-free interval for 3 treatment cycles. Subjects who received treatment were included in baseline period.

Arm type

Active comparator

Investigational medicinal product name

Ethinyl Estradiol, Levonorgestrel (SH D593B)

Investigational medicinal product code

Other name

Miranova

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Daily oral administration of one tablet placebo plus one tablet SH D593B (Miranova) for 28 days without tablet-free interval for 3 treatment cycles.

Investigational medicinal product name

Placebo Match to SH D593B

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Daily oral administration of one tablet placebo plus one tablet SH D593B (Miranova) for 28 days without tablet-free interval for 3 treatment cycles.

Notes
[1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
Justification: In overall trial, all subjects who were randomized were included and the baseline characteristics were provided only for subjects who were treated. Hence, the baseline period of treated subjects was created to publish the baseline characteristics data.

Number of subjects in period 2	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Started	234	230
Completed	234	230

Baseline characteristics

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Reporting group title

Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)

Reporting group description

Reporting group title

Ethinyl Estradiol, Levonorgestrel (Miranova)

Reporting group description

Reporting group values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)	Total
Number of subjects	234	230	464
Age categorical
Units: Subjects
less than 18 years of age	11	13	24
18 years of age or older	223	217	440
Age continuous
Units: years
arithmetic mean (standard deviation)	28 ( 7.9 )	27.6 ( 8 )	-
Gender categorical
Units: Subjects
Female	234	230	464

End points

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Reporting group title

Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)

Reporting group description

Daily oral administration of one tablet SH T00658ID (BAY86-5027) plus one tablet placebo for 28 days without tablet-free interval for 3 treatment cycles.

Reporting group title

Ethinyl Estradiol, Levonorgestrel (Miranova)

Reporting group description

Daily oral administration of one tablet placebo plus one tablet SH D593B (Miranova) for 28 days without tablet-free interval for 3 treatment cycles.

Reporting group title

Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)

Reporting group description

Reporting group title

Ethinyl Estradiol, Levonorgestrel (Miranova)

Reporting group description

Subject analysis set title

Full analysis set (FAS)

Subject analysis set type

Full analysis

Subject analysis set description

All subjects admitted to the treatment phase who took at least 1 tablet of study medication or comparator, and for whom at least 1 observation after admission to treatment was available were included in the FAS.

Primary: Change Between Baseline Evaluation Period and Treatment Evaluation Period in the Number of Days With Dysmenorrheic Pain

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End point title

Change Between Baseline Evaluation Period and Treatment Evaluation Period in the Number of Days With Dysmenorrheic Pain

End point description

Dysmenorrheic pain was defined as pelvic pain during the menstrual/withdrawal bleeding episode and the 2 days before this episode. Baseline period: 2 days before the first menstrual bleeding until 3rd day before the 3rd menstrual bleeding (normalized to a standard 56-day period). Treatment period: 2 days before the withdrawal bleeding (WB) of the 1st evaluable treatment cycle until 3rd day before the WB of the cycle after the 2nd evaluable treatment cycle (normalized to a standard 56-day period).

End point type

Primary

End point timeframe

Baseline period (2 baseline cycles, usually 56 days) versus (vs) treatment period (on-treatment cycles 2 and 3, usually 56 days)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	225 ^[1]	219 ^[2]
Units: days
arithmetic mean (standard deviation)	-4.6 ( 4.6 )	-4.2 ( 4.2 )

Notes
[1] - FAS
[2] - FAS

Statistical analysis 1

Statistical analysis description

An individual absolute change in days with dysmenorrheic pain from pretreatment was evaluated as number of days with dysmenorrheic pain during the treatment evaluation period minus number of days with dysmenorrheic pain during the pretreatment evaluation period.

Comparison groups

Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027) v Ethinyl Estradiol, Levonorgestrel (Miranova)

Number of subjects included in analysis

444

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3358

Method

t-test, 2-sided

Parameter type

Difference of mean changes from baseline

Point estimate

-0.404

Confidence interval

level

95%

sides

2-sided

lower limit

-1.227

upper limit

0.4196

Secondary: Change Between Baseline Evaluation Period and Treatment Evaluation Period in the Sum of Score Points of Dysmenorrheic Pain

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End point title

Change Between Baseline Evaluation Period and Treatment Evaluation Period in the Sum of Score Points of Dysmenorrheic Pain

End point description

Dysmenorrheic pain: pelvic pain during menstrual/withdrawal bleeding (WB) episode and 2 days before. Scores per day: 0 No pain; 1 Mild pain with no need for painkiller; 2 Moderate pain with need for painkiller; 3 Severe pain with need for painkiller. Baseline period: 2 days before 1st menstrual bleeding until 3rd day before 3rd menstrual bleeding (normalized to standard 56-day period). Treatment period: 2 days before WB of 1st treatment cycle until 3rd day before WB of the cycle after 2nd treatment cycle (normalized to standard 56-day period). Score difference minimum -168 (best), maximum 168 (worst).

End point type

Secondary

End point timeframe

Baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	225 ^[3]	219 ^[4]
Units: scores on a scale
arithmetic mean (standard deviation)	-10.6 ( 9.7 )	-10 ( 8.9 )

Notes
[3] - FAS
[4] - FAS

No statistical analyses for this end point

Secondary: Change Between Baseline Evaluation Period and Treatment Evaluation Period in Number of Days With Pelvic Pain Independent of Occurrence of Vaginal Bleeding

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End point title

Change Between Baseline Evaluation Period and Treatment Evaluation Period in Number of Days With Pelvic Pain Independent of Occurrence of Vaginal Bleeding

End point description

Baseline period: 2 days before the first menstrual bleeding until 3rd day before the 3rd menstrual bleeding (normalized to a standard 56-day period). Treatment period: 2 days before the withdrawal bleeding (WB) of the 1st evaluable treatment cycle until 3rd day before the WB of the cycle after the 2nd evaluable treatment cycle (normalized to a standard 56-day period).

End point type

Secondary

End point timeframe

Baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	225 ^[5]	219 ^[6]
Units: days
arithmetic mean (standard deviation)	-4 ( 5.7 )	-3.7 ( 5.7 )

Notes
[5] - FAS
[6] - FAS

No statistical analyses for this end point

Secondary: Change Between Baseline Evaluation Period and Treatment Evaluation Period in Number of Days With Pelvic Pain During Unscheduled Bleeding

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End point title

Change Between Baseline Evaluation Period and Treatment Evaluation Period in Number of Days With Pelvic Pain During Unscheduled Bleeding

End point description

Evaluated was the number of days with bleeding-associated pelvic pain, excluding days during withdrawal bleeding (WB) and the 2 days preceding such WB, and during administration deviation bleeding and the 2 days preceding such bleeding (normalized to a standard 56-day period). Baseline period: 2 days before first menstrual bleeding until 3rd day before 3rd menstrual bleeding (normalized to standard 56-day period). Treatment period: 2 days before WB of the 1st treatment cycle until 3rd day before the WB of the cycle after the 2nd treatment cycle (normalized to standard 56-day period).

End point type

Secondary

End point timeframe

Baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	225 ^[7]	219 ^[8]
Units: days
arithmetic mean (standard deviation)	0.3 ( 2.6 )	0.1 ( 2 )

Notes
[7] - FAS
[8] - FAS

No statistical analyses for this end point

Secondary: Change Between Baseline Evaluation Period and Treatment Evaluation Period in Rescue Medication Use (Only Bleeding Episodes Used Including the Two Days Before the Episode)

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End point title

Change Between Baseline Evaluation Period and Treatment Evaluation Period in Rescue Medication Use (Only Bleeding Episodes Used Including the Two Days Before the Episode)

End point description

Rescue medication use was standardized intake of 200 mg Ibuprofen tablets. Baseline period: 2 days before the first menstrual bleeding until 3rd day before the 3rd menstrual bleeding (normalized to a standard 56-day period). Treatment period: 2 days before the withdrawal bleeding (WB) of the 1st evaluable treatment cycle until 3rd day before the WB of the cycle after the 2nd evaluable treatment cycle (normalized to a standard 56-day period).

End point type

Secondary

End point timeframe

Baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	225 ^[9]	219 ^[10]
Units: tablets
arithmetic mean (standard deviation)	-6.2 ( 14.8 )	-6.6 ( 12.3 )

Notes
[9] - FAS
[10] - FAS

No statistical analyses for this end point

Secondary: Change Between Baseline Evaluation Period and Treatment Evaluation Period in Rescue Medication Use (Entire Evaluation Period Used)

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End point title

Change Between Baseline Evaluation Period and Treatment Evaluation Period in Rescue Medication Use (Entire Evaluation Period Used)

End point description

End point type

Secondary

End point timeframe

Baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	225 ^[11]	219 ^[12]
Units: tablets
arithmetic mean (standard deviation)	-4.5 ( 19.9 )	-5.6 ( 14.3 )

Notes
[11] - FAS
[12] - FAS

No statistical analyses for this end point

Secondary: Percentage of Subjects With Interference of Dysmenorrheic Pain With Work/School and Social or Other Activity (Only Bleeding Episodes Used Including the Two Days Before)

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End point title

Percentage of Subjects With Interference of Dysmenorrheic Pain With Work/School and Social or Other Activity (Only Bleeding Episodes Used Including the Two Days Before)

End point description

Interference of dysmenorrheic pain with work/school and social or other activity was assessed (yes/no). Baseline period: 2 days before the first menstrual bleeding until 3rd day before the 3rd menstrual bleeding (normalized to a standard 56-day period). Treatment period: 2 days before the withdrawal bleeding (WB) of the 1st evaluable treatment cycle until 3rd day before the WB of the cycle after the 2nd evaluable treatment cycle (normalized to a standard 56-day period).

End point type

Secondary

End point timeframe

Baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	234 ^[13]	230 ^[14]
Units: percentage of subjects
number (not applicable)
Baseline period-daily activities impaired	92.3	91.3
Baseline period- leisure activities impaired	90.6	89.6
Treatment period-daily activities impaired	51.7	56.5
Treatment period- leisure activities impaired	47.9	56.5

Notes
[13] - FAS
[14] - FAS

No statistical analyses for this end point

Secondary: Percentage of Subjects With Interference of Dysmenorrheic Pain With Work/School and Social or Other Activity (Entire Evaluation Period Used)

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End point title

Percentage of Subjects With Interference of Dysmenorrheic Pain With Work/School and Social or Other Activity (Entire Evaluation Period Used)

End point description

End point type

Secondary

End point timeframe

Baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	234 ^[15]	230 ^[16]
Units: percentage of subjects
number (not applicable)
Baseline period-daily activities impaired	93.2	92.2
Baseline period- leisure activities impaired	92.3	90
Treatment period-daily activities impaired	54.7	60
Treatment period- leisure activities impaired	52.6	61.3

Notes
[15] - FAS
[16] - FAS

No statistical analyses for this end point

Secondary: Percentage of Subjects Satisfied With Study Treatment

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End point title

Percentage of Subjects Satisfied With Study Treatment

End point description

Subjects were asked to express the degree of their satisfaction with study treatment.

End point type

Secondary

End point timeframe

From cycle 1 to cycle 3 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	225 ^[17]	216 ^[18]
Units: percentage of subjects
number (not applicable)
Missing	0.9	1.3
Very satisfied	53.4	50.4
Satisfied	32.1	30
Neither satisfied nor dissatisfied	7.3	8.3
Dissatisfied	2.1	3.5
Very dissatisfied	0.4	0.4

Notes
[17] - FAS
[18] - FAS

No statistical analyses for this end point

Secondary: Number of Days With Bleeding or Spotting

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End point title

Number of Days With Bleeding or Spotting

End point description

Bleeding/spotting episodes (day[s] with bleeding/spotting preceded and followed by at least 2 bleeding/spotting-free days) were described using the reference period (RP) method (length of RP: 90 days) recommended by the World Health Organization. 1st RP started on the 1st day of study medication. The total number of days during bleeding or spotting episodes was counted. Spotting = less than associated with normal menstruation relative to the subject’s experience with no need for sanitary protection (except for panty liners). Bleeding = any bleeding of greater intensity than spotting.

End point type

Secondary

End point timeframe

From day 1 to day 90

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	201 ^[19]	197 ^[20]
Units: days
arithmetic mean (standard deviation)	20 ( 8.8 )	23.6 ( 9.7 )

Notes
[19] - FAS
[20] - FAS

No statistical analyses for this end point

Secondary: Number of Episodes With Bleeding or Spotting

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End point title

Number of Episodes With Bleeding or Spotting

End point description

End point type

Secondary

End point timeframe

From day 1 to day 90

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	201 ^[21]	197 ^[22]
Units: episodes
arithmetic mean (standard deviation)	3.9 ( 1 )	4.1 ( 0.8 )

Notes
[21] - FAS
[22] - FAS

No statistical analyses for this end point

Secondary: Mean Length of Bleeding or Spotting Episodes

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End point title

Mean Length of Bleeding or Spotting Episodes

End point description

End point type

Secondary

End point timeframe

From day 1 to day 90

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	201 ^[23]	197 ^[24]
Units: days
arithmetic mean (standard deviation)	5.17 ( 2.26 )	5.83 ( 2.35 )

Notes
[23] - FAS
[24] - FAS

No statistical analyses for this end point

Secondary: Maximum Length of Bleeding or Spotting Episodes

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End point title

Maximum Length of Bleeding or Spotting Episodes

End point description

End point type

Secondary

End point timeframe

From day 1 to day 90

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	201 ^[25]	197 ^[26]
Units: days
arithmetic mean (standard deviation)	7.1 ( 3.8 )	8.4 ( 5.6 )

Notes
[25] - FAS
[26] - FAS

No statistical analyses for this end point

Secondary: Difference in Duration Between Longest and Shortest Bleeding or Spotting Episode

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End point title

Difference in Duration Between Longest and Shortest Bleeding or Spotting Episode

End point description

End point type

Secondary

End point timeframe

From day 1 to day 90

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	201 ^[27]	197 ^[28]
Units: days
arithmetic mean (standard deviation)	3.6 ( 3.6 )	4.6 ( 5.6 )

Notes
[27] - FAS
[28] - FAS

No statistical analyses for this end point

Secondary: Number of Days With Spotting-only

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End point title

Number of Days With Spotting-only

End point description

End point type

Secondary

End point timeframe

From day 1 to day 90

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	201 ^[29]	197 ^[30]
Units: days
arithmetic mean (standard deviation)	7.3 ( 6.9 )	7.6 ( 7.5 )

Notes
[29] - FAS
[30] - FAS

No statistical analyses for this end point

Secondary: Number of Episodes With Spotting-only

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End point title

Number of Episodes With Spotting-only

End point description

End point type

Secondary

End point timeframe

From day 1 to day 90

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	201 ^[31]	197 ^[32]
Units: episodes
arithmetic mean (standard deviation)	0.5 ( 0.8 )	0.4 ( 0.7 )

Notes
[31] - FAS
[32] - FAS

No statistical analyses for this end point

Secondary: Mean Length of Spotting Only Episodes

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End point title

Mean Length of Spotting Only Episodes

End point description

End point type

Secondary

End point timeframe

From day 1 to day 90

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	67 ^[33]	51 ^[34]
Units: days
arithmetic mean (standard deviation)	3.29 ( 2.39 )	3.26 ( 2.79 )

Notes
[33] - FAS
[34] - FAS

No statistical analyses for this end point

Secondary: Maximum Length of Spotting Only Episodes

Top of page

End point title

Maximum Length of Spotting Only Episodes

End point description

End point type

Secondary

End point timeframe

From day 1 to day 90

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	67 ^[35]	51 ^[36]
Units: days
arithmetic mean (standard deviation)	3.9 ( 3.1 )	3.6 ( 3 )

Notes
[35] - FAS
[36] - FAS

No statistical analyses for this end point

Secondary: Difference in Duration Between Longest and Shortest Spotting Only Episode

Top of page

End point title

Difference in Duration Between Longest and Shortest Spotting Only Episode

End point description

End point type

Secondary

End point timeframe

From day 1 to day 90

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	67 ^[37]	51 ^[38]
Units: days
arithmetic mean (standard deviation)	1.2 ( 2.5 )	0.7 ( 1.5 )

Notes
[37] - FAS
[38] - FAS

No statistical analyses for this end point

Secondary: Percentage of Subjects With Withdrawal Bleeding at Cycle 1

Top of page

End point title

Percentage of Subjects With Withdrawal Bleeding at Cycle 1

End point description

Withdrawal bleeding was defined as the first bleeding episode after complete or partial progestogen withdrawal (i.e. the first episode starting after the last day of progestogen intake). If a bleeding episode was ongoing on the last day of progestogen intake and the following day, this episode was regarded as the withdrawal bleeding episode, as long as it had started not more than 4 days before the progestogen withdrawal.

End point type

Secondary

End point timeframe

At cycle 1 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	226 ^[39]	222 ^[40]
Units: percentage of subjects
number (not applicable)	91.2	93.2

Notes
[39] - FAS
[40] - FAS

No statistical analyses for this end point

Secondary: Percentage of Subjects With Withdrawal Bleeding at Cycle 3

Top of page

End point title

Percentage of Subjects With Withdrawal Bleeding at Cycle 3

End point description

End point type

Secondary

End point timeframe

At cycle 3 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	204 ^[41]	198 ^[42]
Units: percentage of subjects
number (not applicable)	68.1	79.3

Notes
[41] - FAS
[42] - FAS

No statistical analyses for this end point

Secondary: Length of Withdrawal Bleeding Episodes at Cycle 1

Top of page

End point title

Length of Withdrawal Bleeding Episodes at Cycle 1

End point description

End point type

Secondary

End point timeframe

At cycle 1 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	206 ^[43]	207 ^[44]
Units: days
arithmetic mean (standard deviation)	5.2 ( 2.7 )	5.4 ( 2.4 )

Notes
[43] - FAS
[44] - FAS

No statistical analyses for this end point

Secondary: Length of Withdrawal Bleeding Episodes at Cycle 3

Top of page

End point title

Length of Withdrawal Bleeding Episodes at Cycle 3

End point description

End point type

Secondary

End point timeframe

At cycle 3 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	139 ^[45]	157 ^[46]
Units: days
arithmetic mean (standard deviation)	4.5 ( 1.7 )	5.2 ( 2 )

Notes
[45] - FAS
[46] - FAS

No statistical analyses for this end point

Secondary: Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 1

Top of page

End point title

Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 1

End point description

End point type

Secondary

End point timeframe

At cycle 1 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	206 ^[47]	207 ^[48]
Units: scores on a scale
arithmetic mean (standard deviation)	3.7 ( 1 )	4 ( 0.9 )

Notes
[47] - FAS
[48] - FAS

No statistical analyses for this end point

Secondary: Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 3

Top of page

End point title

Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 3

End point description

End point type

Secondary

End point timeframe

At cycle 3 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	139 ^[49]	157 ^[50]
Units: scores on a scale
arithmetic mean (standard deviation)	3.7 ( 0.8 )	4.1 ( 0.8 )

Notes
[49] - FAS
[50] - FAS

No statistical analyses for this end point

Secondary: Onset of Withdrawal Bleeding Episodes at Cycle 1

Top of page

End point title

Onset of Withdrawal Bleeding Episodes at Cycle 1

End point description

End point type

Secondary

End point timeframe

At cycle 1 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	206 ^[51]	207 ^[52]
Units: days
arithmetic mean (standard deviation)	4.8 ( 7 )	4.9 ( 5.9 )

Notes
[51] - FAS
[52] - FAS

No statistical analyses for this end point

Secondary: Onset of Withdrawal Bleeding Episodes at Cycle 3

Top of page

End point title

Onset of Withdrawal Bleeding Episodes at Cycle 3

End point description

End point type

Secondary

End point timeframe

At cycle 3 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	139 ^[53]	157 ^[54]
Units: days
arithmetic mean (standard deviation)	3.1 ( 3.7 )	4.3 ( 4.4 )

Notes
[53] - FAS
[54] - FAS

No statistical analyses for this end point

Secondary: Percentage of Subjects With Intracyclic Bleeding at Cycle 1

Top of page

End point title

Percentage of Subjects With Intracyclic Bleeding at Cycle 1

End point description

Intracyclic bleeding episodes were any bleeding episodes not qualifying as withdrawal bleeding. The latter was defined as the first bleeding episode after complete or partial progestogen withdrawal (i.e. the first episode starting after the last day of progestogen intake). If a bleeding episode was ongoing on the last day of progestogen intake and the following day, this episode was regarded as the withdrawal bleeding episode, as long as it had started not more than 4 days before the progestogen withdrawal.

End point type

Secondary

End point timeframe

At cycle 1 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	226 ^[55]	222 ^[56]
Units: percentage of subjects
number (not applicable)	19	16.7

Notes
[55] - FAS
[56] - FAS

No statistical analyses for this end point

Secondary: Percentage of Subjects With Intracyclic Bleeding at Cycle 3

Top of page

End point title

Percentage of Subjects With Intracyclic Bleeding at Cycle 3

End point description

End point type

Secondary

End point timeframe

At cycle 3 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	204 ^[57]	198 ^[58]
Units: percentage of subjects
number (not applicable)	10.8	11.6

Notes
[57] - FAS
[58] - FAS

No statistical analyses for this end point

Secondary: Number of Intracyclic Bleeding Episodes at Cycle 1

Top of page

End point title

Number of Intracyclic Bleeding Episodes at Cycle 1

End point description

End point type

Secondary

End point timeframe

At cycle 1 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	226 ^[59]	222 ^[60]
Units: episodes
arithmetic mean (standard deviation)	0.2 ( 0.5 )	0.2 ( 0.4 )

Notes
[59] - FAS
[60] - FAS

No statistical analyses for this end point

Secondary: Number of Intracyclic Bleeding Episodes at Cycle 3

Top of page

End point title

Number of Intracyclic Bleeding Episodes at Cycle 3

End point description

End point type

Secondary

End point timeframe

At cycle 3 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	204 ^[61]	198 ^[62]
Units: episodes
arithmetic mean (standard deviation)	0.1 ( 0.3 )	0.1 ( 0.4 )

Notes
[61] - FAS
[62] - FAS

No statistical analyses for this end point

Secondary: Maximum Length of Intracyclic Bleeding Episodes at Cycle 1

Top of page

End point title

Maximum Length of Intracyclic Bleeding Episodes at Cycle 1

End point description

End point type

Secondary

End point timeframe

At cycle 1 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	43 ^[63]	37 ^[64]
Units: days
arithmetic mean (standard deviation)	6 ( 5.4 )	6.2 ( 5.7 )

Notes
[63] - FAS
[64] - FAS

No statistical analyses for this end point

Secondary: Maximum Length of Intracyclic Bleeding Episodes at Cycle 3

Top of page

End point title

Maximum Length of Intracyclic Bleeding Episodes at Cycle 3

End point description

End point type

Secondary

End point timeframe

At cycle 3 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	22 ^[65]	23 ^[66]
Units: days
arithmetic mean (standard deviation)	5.5 ( 4.7 )	4.9 ( 4.1 )

Notes
[65] - FAS
[66] - FAS

No statistical analyses for this end point

Secondary: Number of Intracyclic Bleeding Days at Cycle 1

Top of page

End point title

Number of Intracyclic Bleeding Days at Cycle 1

End point description

End point type

Secondary

End point timeframe

At cycle 1 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	226 ^[67]	222 ^[68]
Units: days
arithmetic mean (standard deviation)	1.2 ( 3.5 )	1 ( 3.3 )

Notes
[67] - FAS
[68] - FAS

No statistical analyses for this end point

Secondary: Number of Intracyclic Bleeding Days at Cycle 3

Top of page

End point title

Number of Intracyclic Bleeding Days at Cycle 3

End point description

End point type

Secondary

End point timeframe

At cycle 3 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	204 ^[69]	198 ^[70]
Units: days
arithmetic mean (standard deviation)	0.6 ( 2.3 )	0.6 ( 2.1 )

Notes
[69] - FAS
[70] - FAS

No statistical analyses for this end point

Secondary: Percentage of Subjects With Maximum Intensity of Intracyclic Bleeding Episodes at Cycle 1

Top of page

End point title

Percentage of Subjects With Maximum Intensity of Intracyclic Bleeding Episodes at Cycle 1

End point description

End point type

Secondary

End point timeframe

At cycle 1 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	43 ^[71]	37 ^[72]
Units: percentage of subjects
number (not applicable)
Spotting	53.5	62.2
Light	30.2	10.8
Normal	9.3	13.5
Heavy	7	13.5

Notes
[71] - FAS
[72] - FAS

No statistical analyses for this end point

Secondary: Percentage of Subjects With Maximum Intensity of Intracyclic Bleeding Episodes at Cycle 3

Top of page

End point title

Percentage of Subjects With Maximum Intensity of Intracyclic Bleeding Episodes at Cycle 3

End point description

End point type

Secondary

End point timeframe

At cycle 3 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	22 ^[73]	23 ^[74]
Units: percentage of subjects
number (not applicable)
Spotting	45.5	30.4
Light	27.3	21.7
Normal	13.6	30.4
Heavy	13.6	17.4

Notes
[73] - FAS
[74] - FAS

No statistical analyses for this end point

Secondary: Percentage of Subjects Missing Time From Work Due to Dysmenorrheic Pain at Screening

Top of page

End point title

Percentage of Subjects Missing Time From Work Due to Dysmenorrheic Pain at Screening

End point description

The investigator was asked to interview the subject and record the number of missed hours/days from work due to dysmenorrheic pain in the previous menstrual cycle.

End point type

Secondary

End point timeframe

At screening (28 days)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	234 ^[75]	230 ^[76]
Units: percentage of subjects
number (not applicable)
Missing	0.4	0
Never	38	40.4
4 working hours	16.2	16.1
1 working day	26.5	29.6
>= 2 working days	18.8	13.9

Notes
[75] - FAS
[76] - FAS

No statistical analyses for this end point

Secondary: Percentage of Subjects Missing Time From Work Due to Dysmenorrheic Pain at Baseline Cycle

Top of page

End point title

Percentage of Subjects Missing Time From Work Due to Dysmenorrheic Pain at Baseline Cycle

End point description

The investigator was asked to interview the subject and record the number of missed hours/days from work due to dysmenorrheic pain in the previous menstrual cycle.

End point type

Secondary

End point timeframe

At Baseline (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	234 ^[77]	229 ^[78]
Units: percentage of subjects
number (not applicable)
Missing	0	0
Never	47.9	51.7
4 working hours	13.2	11.7
1 working day	20.9	23.9
>= 2 working days	17.9	12.2

Notes
[77] - FAS
[78] - FAS

No statistical analyses for this end point

Secondary: Percentage of Subjects Missing Time From Work Due to Dysmenorrheic Pain at Cycle 2

Top of page

End point title

Percentage of Subjects Missing Time From Work Due to Dysmenorrheic Pain at Cycle 2

End point description

The investigator was asked to interview the subject and record the number of missed hours/days from work due to dysmenorrheic pain in the previous menstrual cycle.

End point type

Secondary

End point timeframe

At cycle 2 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	224 ^[79]	212 ^[80]
Units: percentage of subjects
number (not applicable)
Missing	0	0
Never	78.6	72.6
4 working hours	8.5	6.5
1 working day	6.4	8.7
>= 2 working days	2.1	4.3

Notes
[79] - FAS
[80] - FAS

No statistical analyses for this end point

Secondary: Percentage of Subjects Missing Time From Work Due to Dysmenorrheic Pain at Final Examination

Top of page

End point title

Percentage of Subjects Missing Time From Work Due to Dysmenorrheic Pain at Final Examination

End point description

The investigator was asked to interview the subject and record the number of missed hours/days from work due to dysmenorrheic pain in the previous menstrual cycle.

End point type

Secondary

End point timeframe

At final examination (28 days)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	226 ^[81]	217 ^[82]
Units: percentage of subjects
number (not applicable)
Missing	0.4	0
Never	85.9	85.2
4 working hours	5.6	2.6
1 working day	3	4.8
>= 2 working days	1.7	1.7

Notes
[81] - FAS
[82] - FAS

No statistical analyses for this end point

Secondary: Own Costs of Physiotherapy Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire

Top of page

End point title

Own Costs of Physiotherapy Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire

End point description

The subjects were asked to complete a resource use questionnaire indicating their own costs of physiotherapy per treatment of dysmenorrheic pain. Costs were converted to U.S. dollars.

End point type

Secondary

End point timeframe

At screening (average over 3 months before screening)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	173 ^[83]	174 ^[84]
Units: dollars
median (full range (min-max))	0 (0 to 0)	0 (0 to 0)

Notes
[83] - FAS
[84] - FAS

No statistical analyses for this end point

Secondary: Own Costs of Pain Medication Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire

Top of page

End point title

Own Costs of Pain Medication Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire

End point description

The subjects were asked to complete a resource use questionnaire indicating their own costs of pain medication per treatment of dysmenorrheic pain. Costs were converted to U.S. dollars.

End point type

Secondary

End point timeframe

At screening (average over 3 months before screening)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	206 ^[85]	195 ^[86]
Units: dollars
median (full range (min-max))	5.46 (0 to 30)	5.04 (0 to 27.49)

Notes
[85] - FAS
[86] - FAS

No statistical analyses for this end point

Secondary: Own Costs of Vitamins Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire

Top of page

End point title

Own Costs of Vitamins Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire

End point description

The subjects were asked to complete a resource use questionnaire indicating their own costs of vitamins per treatment of dysmenorrheic pain. Costs were converted to U.S. dollars.

End point type

Secondary

End point timeframe

At screening (average over 3 months before screening)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	173 ^[87]	176 ^[88]
Units: dollars
median (full range (min-max))	0 (0 to 65.45)	0 (0 to 65.45)

Notes
[87] - FAS
[88] - FAS

No statistical analyses for this end point

Secondary: Own Costs of Massages Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire

Top of page

End point title

Own Costs of Massages Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire

End point description

The subjects were asked to complete a resource use questionnaire indicating their own costs of massages per treatment of dysmenorrheic pain. Costs were converted to U.S. dollars.

End point type

Secondary

End point timeframe

At screening (average over 3 months before screening)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	172 ^[89]	172 ^[90]
Units: dollars
median (full range (min-max))	0 (0 to 60)	0 (0 to 295.98)

Notes
[89] - FAS
[90] - FAS

No statistical analyses for this end point

Secondary: Own Costs of Acupuncture Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire

Top of page

End point title

Own Costs of Acupuncture Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire

End point description

The subjects were asked to complete a resource use questionnaire indicating their own costs of acupuncture per treatment of dysmenorrheic pain. Costs were converted to U.S. dollars.

End point type

Secondary

End point timeframe

At screening (average over 3 months before screening)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	174 ^[91]	174 ^[92]
Units: dollars
median (full range (min-max))	0 (0 to 150)	0 (0 to 74)

Notes
[91] - FAS
[92] - FAS

No statistical analyses for this end point

Secondary: Own Costs of Medical Counseling Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire

Top of page

End point title

Own Costs of Medical Counseling Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire

End point description

The subjects were asked to complete a resource use questionnaire indicating their own costs ofmedical counseling per treatment of dysmenorrheic pain. Costs were converted to U.S. dollars.

End point type

Secondary

End point timeframe

At screening (average over 3 months before screening)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	170 ^[93]	170 ^[94]
Units: dollars
median (full range (min-max))	0 (0 to 271.68)	0 (0 to 98.17)

Notes
[93] - FAS
[94] - FAS

No statistical analyses for this end point

Secondary: Own Costs of Alternative Medicine Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire

Top of page

End point title

Own Costs of Alternative Medicine Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire

End point description

The subjects were asked to complete a resource use questionnaire indicating their other own costs of alternative medicine per treatment of dysmenorrheic pain. Costs were converted to U.S. dollars.

End point type

Secondary

End point timeframe

At screening (average over 3 months before screening)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	177 ^[95]	175 ^[96]
Units: dollars
median (full range (min-max))	0 (0 to 196.34)	0 (0 to 110)

Notes
[95] - FAS
[96] - FAS

No statistical analyses for this end point

Secondary: Own Costs of Herbs/Teas Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire

Top of page

End point title

Own Costs of Herbs/Teas Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire

End point description

The subjects were asked to complete a resource use questionnaire indicating their own costs of herbs/teas per treatment of dysmenorrheic pain. Costs were converted to U.S. dollars.

End point type

Secondary

End point timeframe

At screening (average over 3 months before screening)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	183 ^[97]	179 ^[98]
Units: dollars
median (full range (min-max))	0 (0 to 30)	0 (0 to 10)

Notes
[97] - FAS
[98] - FAS

No statistical analyses for this end point

Secondary: Other Own Costs Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire

Top of page

End point title

Other Own Costs Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire

End point description

The subjects were asked to complete a resource use questionnaire indicating their other own costs per treatment of dysmenorrheic pain. Costs were converted to U.S. dollars.

End point type

Secondary

End point timeframe

At screening (average over 3 months before screening)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	192 ^[99]	194 ^[100]
Units: dollars
median (full range (min-max))	0 (0 to 15)	0 (0 to 42)

Notes
[99] - FAS
[100] - FAS

No statistical analyses for this end point

Secondary: Subjects With Improvement in the Investigators' Assessment in the Clinical Global Impression

Top of page

End point title

Subjects With Improvement in the Investigators' Assessment in the Clinical Global Impression

End point description

The Clinical Global Impression Scale (CGI) is a widely used rating scale/assessment instrument in psychopharmacology research in general, and in studies on women’s health in particular. Investigators were asked to rate the subjects' improvement during the course of the study.

End point type

Secondary

End point timeframe

At cycle 2 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	223 ^[101]	210 ^[102]
Units: subjects
Missing	0	0
Not assessed	1	1
Very much improved	63	42
Much improved	87	84
Minimally improved	49	54
No change	17	23
Minimally worse	6	3
Much worse	0	3

Notes
[101] - FAS
[102] - FAS

No statistical analyses for this end point

Secondary: Subjects With Improvement in Subjects' Assessment in the Clinical Global Impression

Top of page

End point title

Subjects With Improvement in Subjects' Assessment in the Clinical Global Impression

End point description

The CGI is a widely used rating scale/assessment instrument in psychopharmacology research in general, and in studies on women’s health in particular. Subjects were asked to rate their improvement during the course of the study.

End point type

Secondary

End point timeframe

At cycle 2 (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	223 ^[103]	210 ^[104]
Units: subjects
Missing	1	0
Not assessed	1	1
Very much improved	60	46
Much improved	91	75
Minimally improved	47	57
No change	18	24
Minimally worse	5	4
Much worse	0	3

Notes
[103] - FAS
[104] - FAS

No statistical analyses for this end point

Secondary: Physical Functioning as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle

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End point title

Physical Functioning as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle

End point description

The standard questionnaire SF-36 version 1 (v1), a general health status measure used to evaluate subject populations and to compare health status across different populations, was completed by subjects as a self-administered native language version. Percentages of absolute scores were calculated such that 0 represents the lowest possible score (worst outcome) and 100 the highest possible score (best outcome).

End point type

Secondary

End point timeframe

At baseline cycle (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	234 ^[105]	229 ^[106]
Units: scores on a scale
arithmetic mean (standard deviation)	90.2 ( 16.7 )	89.6 ( 17.5 )

Notes
[105] - FAS
[106] - FAS

No statistical analyses for this end point

Secondary: Physical Functioning as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination

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End point title

Physical Functioning as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination

End point description

The standard questionnaire SF-36 v1, a general health status measure used to evaluate subject populations and to compare health status across different populations, was completed by subjects as a self-administered native language version. Percentages of absolute scores were calculated such that 0 represents the lowest possible score (worst outcome) and 100 the highest possible score (best outcome).

End point type

Secondary

End point timeframe

At final examination (28 days)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	226 ^[107]	217 ^[108]
Units: scores on a scale
arithmetic mean (standard deviation)	93.7 ( 14.2 )	92.5 ( 15 )

Notes
[107] - FAS
[108] - FAS

No statistical analyses for this end point

Secondary: Social Functioning as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle

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End point title

Social Functioning as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle

End point description

The standard questionnaire SF-36v1, a general health status measure used to evaluate subject populations and to compare health status across different populations, was completed by subjects as a self-administered native language version. Percentages of absolute scores were calculated such that 0 represents the lowest possible score (worst outcome) and 100 the highest possible score (best outcome).

End point type

Secondary

End point timeframe

At baseline cycle (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	234 ^[109]	229 ^[110]
Units: scores on a scale
arithmetic mean (standard deviation)	78.85 ( 18.99 )	77.35 ( 20.56 )

Notes
[109] - FAS
[110] - FAS

No statistical analyses for this end point

Secondary: Social Functioning as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination

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End point title

Social Functioning as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination

End point description

The standard questionnaire SF-36v1, a general health status measure used to evaluate subject populations and to compare health status across different populations, was completed by subjects as a self-administered native language version. Percentages of absolute scores were calculated such that 0 represents the lowest possible score (worst outcome) and 100 the highest possible score (best outcome).

End point type

Secondary

End point timeframe

At final examination (28 days)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	226 ^[111]	217 ^[112]
Units: scores on a scale
arithmetic mean (standard deviation)	85.95 ( 19.09 )	84.79 ( 17.36 )

Notes
[111] - FAS
[112] - FAS

No statistical analyses for this end point

Secondary: Mental Health as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle

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End point title

Mental Health as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle

End point description

The standard questionnaire SF-36v1, a general health status measure used to evaluate patient populations and to compare health status across different populations, was completed by subjects as a self-administered native language version. Percentages of absolute scores were calculated such that 0 represents the lowest possible score (worst outcome) and 100 the highest possible score (best outcome).

End point type

Secondary

End point timeframe

At baseline cycle (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	234 ^[113]	229 ^[114]
Units: scores on a scale
arithmetic mean (standard deviation)	73.6 ( 15.6 )	72.6 ( 16.3 )

Notes
[113] - FAS
[114] - FAS

No statistical analyses for this end point

Secondary: Mental Health as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination

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End point title

Mental Health as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination

End point description

The standard questionnaire SF-36v1, a general health status measure used to evaluate subject populations and to compare health status across different populations, was completed by subjects as a self-administered native language version. Percentages of absolute scores were calculated such that 0 represents the lowest possible score (worst outcome) and 100 the highest possible score (best outcome).

End point type

Secondary

End point timeframe

At final examination (28 days)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	226 ^[115]	217 ^[116]
Units: scores on a scale
arithmetic mean (standard deviation)	77.3 ( 14.9 )	76.4 ( 14.7 )

Notes
[115] - FAS
[116] - FAS

No statistical analyses for this end point

Secondary: Vitality as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle

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End point title

Vitality as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle

End point description

The standard questionnaire SF-36v1, a general health status measure used to evaluate subject populations and to compare health status across different populations, was completed by subjects as a self-administered native language version. Percentages of absolute scores were calculated such that 0 represents the lowest possible score (worst outcome) and 100 the highest possible score (best outcome).

End point type

Secondary

End point timeframe

At baseline cycle (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	234 ^[117]	229 ^[118]
Units: scores on a scale
arithmetic mean (standard deviation)	62.6 ( 18 )	62.2 ( 18.2 )

Notes
[117] - FAS
[118] - FAS

No statistical analyses for this end point

Secondary: Vitality as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination

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End point title

Vitality as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination

End point description

The standard questionnaire SF-36v1, a general health status measure used to evaluate subject populations and to compare health status across different populations, was completed by subjects as a self-administered native language version. Percentages of absolute scores were calculated such that 0 represents the lowest possible score (worst outcome) and 100 the highest possible score (best outcome).

End point type

Secondary

End point timeframe

At final examination (28 days)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	226 ^[119]	217 ^[120]
Units: scores on a scale
arithmetic mean (standard deviation)	68.2 ( 17 )	67.2 ( 16.8 )

Notes
[119] - FAS
[120] - FAS

No statistical analyses for this end point

Secondary: General Health as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle

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End point title

General Health as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle

End point description

The standard questionnaire SF-36v1, a general health status measure used to evaluate subject populations and to compare health status across different populations, was completed by subjects as a self-administered native language version. Percentages of absolute scores were calculated such that 0 represents the lowest possible score (worst outcome) and 100 the highest possible score (best outcome).

End point type

Secondary

End point timeframe

At baseline cycle (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	234 ^[121]	229 ^[122]
Units: scores on a scale
arithmetic mean (standard deviation)	75.8 ( 17.5 )	72.7 ( 16.9 )

Notes
[121] - FAS
[122] - FAS

No statistical analyses for this end point

Secondary: General Health as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination

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End point title

General Health as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination

End point description

The standard questionnaire SF-36v1, a general health status measure used to evaluate subject populations and to compare health status across different populations, was completed by subjects as a self-administered native language version. Percentages of absolute scores were calculated such that 0 represents the lowest possible score (worst outcome) and 100 the highest possible score (best outcome).

End point type

Secondary

End point timeframe

At final examination (28 days)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	226 ^[123]	217 ^[124]
Units: scores on a scale
arithmetic mean (standard deviation)	77.2 ( 17.9 )	76.5 ( 16.6 )

Notes
[123] - FAS
[124] - FAS

No statistical analyses for this end point

Secondary: Role Physical as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle

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End point title

Role Physical as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle

End point description

The standard questionnaire SF-36v1, a general health status measure used to evaluate subject populations and to compare health status across different populations, was completed by subjects as a self-administered native language version. Percentages of absolute scores were calculated such that 0 represents the lowest possible score (worst outcome) and 100 the highest possible score (best outcome).

End point type

Secondary

End point timeframe

At baseline cycle (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	234 ^[125]	229 ^[126]
Units: scores on a scale
arithmetic mean (standard deviation)	77.8 ( 33.6 )	79.4 ( 32.7 )

Notes
[125] - FAS
[126] - FAS

No statistical analyses for this end point

Secondary: Role Physical as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination

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End point title

Role Physical as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination

End point description

The standard questionnaire SF-36v1, a general health status measure used to evaluate subject populations and to compare health status across different populations, was completed by subjects as a self-administered native language version. Percentages of absolute scores were calculated such that 0 represents the lowest possible score (worst outcome) and 100 the highest possible score (best outcome).

End point type

Secondary

End point timeframe

At final examination (28 days)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	226 ^[127]	217 ^[128]
Units: scores on a scale
arithmetic mean (standard deviation)	89.6 ( 23 )	87.9 ( 25.9 )

Notes
[127] - FAS
[128] - FAS

No statistical analyses for this end point

Secondary: Role Emotional as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle

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End point title

Role Emotional as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle

End point description

The standard questionnaire SF-36v1, a general health status measure used to evaluate subject populations and to compare health status across different populations, was completed by subjects as a self-administered native language version. Percentages of absolute scores were calculated such that 0 represents the lowest possible score (worst outcome) and 100 the highest possible score (best outcome).

End point type

Secondary

End point timeframe

At baseline cycle (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	234 ^[129]	229 ^[130]
Units: scores on a scale
arithmetic mean (standard deviation)	81.91 ( 31.5 )	79.18 ( 34.74 )

Notes
[129] - FAS
[130] - FAS

No statistical analyses for this end point

Secondary: Role Emotional as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination

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End point title

Role Emotional as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination

End point description

The standard questionnaire SF-36v1, a general health status measure used to evaluate subject populations and to compare health status across different populations, was completed by subjects as a self-administered native language version. Percentages of absolute scores were calculated such that 0 represents the lowest possible score (worst outcome) and 100 the highest possible score (best outcome).

End point type

Secondary

End point timeframe

At final examination (28 days)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	226 ^[131]	217 ^[132]
Units: scores on a scale
arithmetic mean (standard deviation)	88.64 ( 26.36 )	83.87 ( 30.28 )

Notes
[131] - FAS
[132] - FAS

No statistical analyses for this end point

Secondary: Bodily Pain as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle

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End point title

Bodily Pain as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle

End point description

The standard questionnaire SF-36v1, a general health status measure used to evaluate subject populations and to compare health status across different populations, was completed by subjects as a self-administered native language version. Percentages of absolute scores were calculated such that 0 represents the lowest possible score (worst outcome) and 100 the highest possible score (best outcome).

End point type

Secondary

End point timeframe

At baseline cycle (28 days per cycle)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	234 ^[133]	229 ^[134]
Units: scores on a scale
arithmetic mean (standard deviation)	50.7 ( 24.4 )	51.8 ( 23 )

Notes
[133] - FAS
[134] - FAS

No statistical analyses for this end point

Secondary: Bodily Pain as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination

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End point title

Bodily Pain as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination

End point description

The standard questionnaire SF-36v1, a general health status measure used to evaluate subject populations and to compare health status across different populations, was completed by subjects as a self-administered native language version. Percentages of absolute scores were calculated such that 0 represents the lowest possible score (worst outcome) and 100 the highest possible score (best outcome).

End point type

Secondary

End point timeframe

At final examination (28 days)

End point values	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)	Ethinyl Estradiol, Levonorgestrel (Miranova)
Number of subjects analysed	226 ^[135]	217 ^[136]
Units: scores on a scale
arithmetic mean (standard deviation)	77 ( 21.5 )	74 ( 22.1 )

Notes
[135] - FAS
[136] - FAS

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From treatment period (on-treatment cycles 2 and 3, usually 56 days) up to end of study visit (visit 4, final examination, 28 days)

Adverse event reporting additional description

Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

13.1

Reporting group title

Ethinyl Estradiol, Levonorgestrel (Miranova)

Reporting group description

Reporting group title

Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)

Reporting group description

Serious adverse events	Ethinyl Estradiol, Levonorgestrel (Miranova)	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 230 (0.87%)	2 / 234 (0.85%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Injury, poisoning and procedural complications
Animal bite
subjects affected / exposed	1 / 230 (0.43%)	0 / 234 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian torsion
subjects affected / exposed	0 / 230 (0.00%)	1 / 234 (0.43%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed	1 / 230 (0.43%)	0 / 234 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Helminthic infection
subjects affected / exposed	0 / 230 (0.00%)	1 / 234 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Ethinyl Estradiol, Levonorgestrel (Miranova)	Estradiol Valerate, Dienogest (Natazia, Qlaira, BAY86-5027)
Total subjects affected by non serious adverse events
subjects affected / exposed	122 / 230 (53.04%)	131 / 234 (55.98%)
Nervous system disorders
Headache
subjects affected / exposed	34 / 230 (14.78%)	32 / 234 (13.68%)
occurrences all number	55	55
Tension headache
subjects affected / exposed	9 / 230 (3.91%)	14 / 234 (5.98%)
occurrences all number	43	40
General disorders and administration site conditions
Inflammation
subjects affected / exposed	3 / 230 (1.30%)	7 / 234 (2.99%)
occurrences all number	3	7
Gastrointestinal disorders
Dental caries
subjects affected / exposed	2 / 230 (0.87%)	5 / 234 (2.14%)
occurrences all number	7	10
Nausea
subjects affected / exposed	5 / 230 (2.17%)	2 / 234 (0.85%)
occurrences all number	6	2
Reproductive system and breast disorders
Cervical dysplasia
subjects affected / exposed	9 / 230 (3.91%)	7 / 234 (2.99%)
occurrences all number	9	7
Dysfunctional uterine bleeding
subjects affected / exposed	5 / 230 (2.17%)	3 / 234 (1.28%)
occurrences all number	6	4
Dysmenorrhoea
subjects affected / exposed	82 / 230 (35.65%)	87 / 234 (37.18%)
occurrences all number	210	208
Metrorrhagia
subjects affected / exposed	13 / 230 (5.65%)	18 / 234 (7.69%)
occurrences all number	17	28
Cervix inflammation
subjects affected / exposed	4 / 230 (1.74%)	9 / 234 (3.85%)
occurrences all number	4	9
Infections and infestations
Influenza
subjects affected / exposed	5 / 230 (2.17%)	2 / 234 (0.85%)
occurrences all number	5	2
Upper respiratory tract infection
subjects affected / exposed	7 / 230 (3.04%)	4 / 234 (1.71%)
occurrences all number	10	6

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

19 Feb 2009

Amendment 1 was globally implemented before the inclusion of the first subject in the study. As an adequate (re-)supply for the originally planned comparator (Alesse) was not considered feasible, Alesse was replaced by SH D593B (Miranova), and the originally intended encapsulation of tablets for blinding was replaced by a double-dummy design that was considered to have advantages for the subjects, study drug supply and the study as a whole.

26 Aug 2009

Amendment 2 was globally implemented to reflect revised rules to be observed in case of missed tablets to further improve readability. These revised rules had been submitted with the regulatory submission of SH T00658ID to the Food and Drug Administration (FDA) on 02 Jul 2009. In addition, according to the general recommendations for combined oral contraceptive users, the maximum age for smokers to be eligible for this study was changed from 30 to 35 years.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A multi-center, double-blind, double-dummy, randomized, controlled, parallel-group study to assess efficacy and safety of SH T00658ID compared to SH D593B in the treatment of primary dysmenorrhea

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change Between Baseline Evaluation Period and Treatment Evaluation Period in the Number of Days With Dysmenorrheic Pain

Primary: Change Between Baseline Evaluation Period and Treatment Evaluation Period in the Number of Days With Dysmenorrheic Pain

Secondary: Change Between Baseline Evaluation Period and Treatment Evaluation Period in the Sum of Score Points of Dysmenorrheic Pain

Secondary: Change Between Baseline Evaluation Period and Treatment Evaluation Period in the Sum of Score Points of Dysmenorrheic Pain

Secondary: Change Between Baseline Evaluation Period and Treatment Evaluation Period in Number of Days With Pelvic Pain Independent of Occurrence of Vaginal Bleeding

Secondary: Change Between Baseline Evaluation Period and Treatment Evaluation Period in Number of Days With Pelvic Pain Independent of Occurrence of Vaginal Bleeding

Secondary: Change Between Baseline Evaluation Period and Treatment Evaluation Period in Number of Days With Pelvic Pain During Unscheduled Bleeding

Secondary: Change Between Baseline Evaluation Period and Treatment Evaluation Period in Number of Days With Pelvic Pain During Unscheduled Bleeding

Secondary: Change Between Baseline Evaluation Period and Treatment Evaluation Period in Rescue Medication Use (Only Bleeding Episodes Used Including the Two Days Before the Episode)

Secondary: Change Between Baseline Evaluation Period and Treatment Evaluation Period in Rescue Medication Use (Only Bleeding Episodes Used Including the Two Days Before the Episode)

Secondary: Change Between Baseline Evaluation Period and Treatment Evaluation Period in Rescue Medication Use (Entire Evaluation Period Used)

Secondary: Change Between Baseline Evaluation Period and Treatment Evaluation Period in Rescue Medication Use (Entire Evaluation Period Used)

Secondary: Percentage of Subjects With Interference of Dysmenorrheic Pain With Work/School and Social or Other Activity (Only Bleeding Episodes Used Including the Two Days Before)

Secondary: Percentage of Subjects With Interference of Dysmenorrheic Pain With Work/School and Social or Other Activity (Only Bleeding Episodes Used Including the Two Days Before)

Secondary: Percentage of Subjects With Interference of Dysmenorrheic Pain With Work/School and Social or Other Activity (Entire Evaluation Period Used)

Secondary: Percentage of Subjects With Interference of Dysmenorrheic Pain With Work/School and Social or Other Activity (Entire Evaluation Period Used)

Secondary: Percentage of Subjects Satisfied With Study Treatment

Secondary: Percentage of Subjects Satisfied With Study Treatment

Secondary: Number of Days With Bleeding or Spotting

Secondary: Number of Days With Bleeding or Spotting

Secondary: Number of Episodes With Bleeding or Spotting

Secondary: Number of Episodes With Bleeding or Spotting

Secondary: Mean Length of Bleeding or Spotting Episodes

Secondary: Mean Length of Bleeding or Spotting Episodes

Secondary: Maximum Length of Bleeding or Spotting Episodes

Secondary: Maximum Length of Bleeding or Spotting Episodes

Secondary: Difference in Duration Between Longest and Shortest Bleeding or Spotting Episode

Secondary: Difference in Duration Between Longest and Shortest Bleeding or Spotting Episode

Secondary: Number of Days With Spotting-only

Secondary: Number of Days With Spotting-only

Secondary: Number of Episodes With Spotting-only

Secondary: Number of Episodes With Spotting-only

Secondary: Mean Length of Spotting Only Episodes

Secondary: Mean Length of Spotting Only Episodes

Secondary: Maximum Length of Spotting Only Episodes

Secondary: Maximum Length of Spotting Only Episodes

Secondary: Difference in Duration Between Longest and Shortest Spotting Only Episode

Secondary: Difference in Duration Between Longest and Shortest Spotting Only Episode

Secondary: Percentage of Subjects With Withdrawal Bleeding at Cycle 1

Secondary: Percentage of Subjects With Withdrawal Bleeding at Cycle 1

Secondary: Percentage of Subjects With Withdrawal Bleeding at Cycle 3

Secondary: Percentage of Subjects With Withdrawal Bleeding at Cycle 3

Secondary: Length of Withdrawal Bleeding Episodes at Cycle 1

Secondary: Length of Withdrawal Bleeding Episodes at Cycle 1

Secondary: Length of Withdrawal Bleeding Episodes at Cycle 3

Secondary: Length of Withdrawal Bleeding Episodes at Cycle 3

Secondary: Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 1

Secondary: Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 1

Secondary: Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 3

Secondary: Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 3

Secondary: Onset of Withdrawal Bleeding Episodes at Cycle 1

Secondary: Onset of Withdrawal Bleeding Episodes at Cycle 1

Secondary: Onset of Withdrawal Bleeding Episodes at Cycle 3

Secondary: Onset of Withdrawal Bleeding Episodes at Cycle 3

Secondary: Percentage of Subjects With Intracyclic Bleeding at Cycle 1

Secondary: Percentage of Subjects With Intracyclic Bleeding at Cycle 1

Secondary: Percentage of Subjects With Intracyclic Bleeding at Cycle 3

Secondary: Percentage of Subjects With Intracyclic Bleeding at Cycle 3

Secondary: Number of Intracyclic Bleeding Episodes at Cycle 1

Secondary: Number of Intracyclic Bleeding Episodes at Cycle 1

Secondary: Number of Intracyclic Bleeding Episodes at Cycle 3

Secondary: Number of Intracyclic Bleeding Episodes at Cycle 3

Secondary: Maximum Length of Intracyclic Bleeding Episodes at Cycle 1

Secondary: Maximum Length of Intracyclic Bleeding Episodes at Cycle 1

Secondary: Maximum Length of Intracyclic Bleeding Episodes at Cycle 3

Secondary: Maximum Length of Intracyclic Bleeding Episodes at Cycle 3

Secondary: Number of Intracyclic Bleeding Days at Cycle 1

Secondary: Number of Intracyclic Bleeding Days at Cycle 1

Secondary: Number of Intracyclic Bleeding Days at Cycle 3

Secondary: Number of Intracyclic Bleeding Days at Cycle 3

Clinical Trial Results:
A multi-center, double-blind, double-dummy, randomized, controlled, parallel-group study to assess efficacy and safety of SH T00658ID compared to SH D593B in the treatment of primary dysmenorrhea