Effect on Primary Dysmenorrhea

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

To investigate the potential benefits of a new oral contraceptive (SH T00658ID) on alleviating complaints of dysmenorrhea associated with oral contraceptive use.

Study Overview

• Status: Completed
• Conditions: Primary Dysmenorrhea
• Intervention / Treatment: Drug: Estradiol valerate, Dienogest (Natazia, Qlaira, BAY86-5027); Drug: Placebo Match to SH T00658ID; Drug: Ethinyl estradiol, Levonorgestrel (Miranova); Drug: Placebo Match to SH D593B

• Study Type: Interventional
• Enrollment (Actual): 507
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Langley, British Columbia, Canada, V3A 4H9
  • Ontario
    • Toronto, Ontario, Canada, M5C 2T2
  • Quebec
    • Pointe-Claire, Quebec, Canada, H9R 4S3
    • Ste-Foy, Quebec, Canada, G1V 4X7
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4P 3X1
• Chile
  • Santiago, Chile
  • Santiago de Chile, Chile
  • Talcahuano, Chile
  • Temuco, Chile, 4790711
• Germany
  • Hamburg, Germany, 22159
  • Baden-Württemberg
    • Freiburg, Baden-Württemberg, Germany, 79106
  • Nordrhein-Westfalen
    • Essen, Nordrhein-Westfalen, Germany, 45127
    • Köln, Nordrhein-Westfalen, Germany, 50931
  • Sachsen
    • Leipzig, Sachsen, Germany, 04207
  • Sachsen-Anhalt
    • Bernburg, Sachsen-Anhalt, Germany, 06406
    • Magdeburg, Sachsen-Anhalt, Germany, 39126
• Italy
  • Bologna, Italy, 40138
  • Brescia, Italy, 25123
  • Milano, Italy, 20121
  • Modena, Italy, 41124
  • Perugia, Italy, 06156
  • Roma, Italy, 00161
  • Siena, Italy, 53100
  • Torino, Italy, 10126
  • Udine, Italy, 33100
  • Brindisi
    • Francavilla Fontana, Brindisi, Italy, 72021
• Philippines
  • Cebu, Philippines
  • Cebu City, Philippines
  • Davao, Philippines
  • Metro Manila, Philippines, 1000
  • Metro Manila, Philippines
  • Quezon City, Philippines
• United States
  • Arizona
    • Tucson, Arizona, United States, 85741
  • California
    • San Diego, California, United States, 92108
  • Florida
    • Hialeah, Florida, United States, 33012
    • Leesburg, Florida, United States, 34748
  • Georgia
    • Sandy Springs, Georgia, United States, 30328
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
    • Pittsburgh, Pennsylvania, United States, 15206
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54691

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 50 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Otherwise healthy female subjects requesting contraception and suffering from primary dysmenorrhea with a sum score for dysmenorrheic pain intensity of >/= 8 over 2 baseline cycles documented by a prospective self-rated sum pain score
• Age: 14 - 50 years (inclusive; smokers must not be older than 30 years) at the time point of informed consent
• Normal cervical smear not requiring further follow-up (a cervical smear has to be taken at the screening visit, or a normal result has to be available that was documented within the last 6 months before the screening visit)
• Women with cyclic menstrual bleeding, defined by a cycle length between 25 and 35 days and no amenorrheic cycles or cycles without withdrawal bleeding during the last 3 months prior to visit 1.
• Able to tolerate ibuprofen and willing to use only Ibuprofen supplied for the study.

Exclusion Criteria:

• Pregnancy or lactation (delivery, abortion, or lactation within three cycles before the start of treatment)
• Obesity: body mass index (BMI) > 32 kg/m2
• Hypersensitivity to any of the study drug ingredients
• Any diseases or conditions that might interfere with the conduct of the study or the interpretation of the results
• Presence or a history of venous or arterial thrombotic / thromboembolic events (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction) or of a cerebrovascular accident, including prodromi (e.g. transient ischemic attack, angina pectoris), and conditions that could increase the risk of suffering from any of the above mentioned disorders, e.g. a family history indicating a hereditary predispositionUndiagnosed abnormal genital bleeding
• Abuse of alcohol, drugs, or medicines (e.g. laxatives)

• Other contraceptive methods:

  • Sterilization
  • Oral, vaginal or transdermal hormonal contraception during treatment
  • Intra-uterine devices (IUD) with or without hormone release still in place within 30 days of visit 1
• Simultaneous participation in another clinical trial or participation in another clinical trial prior to study entry that might have an impact on the study objectives at the discretion of the investigator
• Major surgery scheduled for the study period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Estradiol valerate, Dienogest (Natazia, Qlaira, BAY86-5027); 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	Drug: Estradiol valerate, Dienogest (Natazia, Qlaira, BAY86-5027); Daily oral administration of one tablet SH T00658ID for 28 days per cycle in the respective treatment period; no tablet-free interval; Drug: Placebo Match to SH T00658ID; Daily oral administration of one tablet placebo for 28 days without tablet-free interval for 3 treatment cycles.
ACTIVE_COMPARATOR: Ethinyl estradiol, Levonorgestrel (Miranova); Daily oral administration of one tablet placebo plus one tablet SH D593B (Miranova) for 28 days without tablet-free interval for 3 treatment cycles	Drug: Ethinyl estradiol, Levonorgestrel (Miranova); Daily oral administration of one tablet for 28 days per cycle in the respective treatment period; no tablet-free interval; Drug: Placebo Match to SH D593B; Daily oral administration of one tablet placebo for 28 days without tablet-free interval for 3 treatment cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change Between Baseline Evaluation Period and Treatment Evaluation Period in the Number of Days With Dysmenorrheic Pain	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).	baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change Between Baseline Evaluation Period and Treatment Evaluation Period in the Sum of Score Points of Dysmenorrheic Pain	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 min -168 (best), max 168 (worst)	baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)
Change Between Baseline Evaluation Period and Treatment Evaluation Period in Number of Days With Pelvic Pain Independent of Occurrence of Vaginal Bleeding	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).	baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)
Change Between Baseline Evaluation Period and Treatment Evaluation Period in Number of Days With Pelvic Pain During Unscheduled Bleeding	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).	baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)
Change Between Baseline Evaluation Period and Treatment Evaluation Period in Rescue Medication Use (Only Bleeding Episodes Used Including the Two Days Before the Episode)	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).	baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)
Change Between Baseline Evaluation Period and Treatment Evaluation Period in Rescue Medication Use (Entire Evaluation Period Used)	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).	baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)
Percentage of Participants With Interference of Dysmenorrheic Pain With Work/School and Social or Other Activity (Only Bleeding Episodes Used Including the Two Days Before)	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).	baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)
Percentage of Participants With Interference of Dysmenorrheic Pain With Work/School and Social or Other Activity (Entire Evaluation Period Used)	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).	baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)
Percentage of Participants Satisfied With Study Treatment	Participants were asked to express the degree of their satisfaction with study treatment.	From cycle 1 to cycle 3 (28 days per cycle)
Number of Days With Bleeding or Spotting	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.	From day 1 to day 90
Number of Episodes With Bleeding or Spotting	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.	From day 1 to day 90
Mean Length of Bleeding or Spotting Episodes	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.	From day 1 to day 90
Maximum Length of Bleeding or Spotting Episodes	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.	From day 1 to day 90
Difference in Duration Between Longest and Shortest Bleeding or Spotting Episode	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.	From day 1 to day 90
Number of Days With Spotting-only	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.	From day 1 to day 90
Number of Episodes With Spotting-only	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.	From day 1 to day 90
Mean Length of Spotting Only Episodes	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.	From day 1 to day 90
Maximum Length of Spotting Only Episodes	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.	From day 1 to day 90
Difference in Duration Between Longest and Shortest Spotting Only Episode	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.	From day 1 to day 90
Percentage of Participants With Withdrawal Bleeding at Cycle 1	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.	At cycle 1 (28 days per cycle)
Percentage of Participants With Withdrawal Bleeding at Cycle 3	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.	At cycle 3 (28 days per cycle)
Length of Withdrawal Bleeding Episodes at Cycle 1	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.	At cycle 1 (28 days per cycle)
Length of Withdrawal Bleeding Episodes at Cycle 3	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.	At cycle 3 (28 days per cycle)
Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 1	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. Intensity was defined as: 1 = none, 2 = spotting, 3 = light, 4 = normal, 5 = heavy.	At cycle 1 (28 days per cycle)
Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 3	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. Intensity was defined as: 1 = none, 2 = spotting, 3 = light, 4 = normal, 5 = heavy.	At cycle 3 (28 days per cycle)
Onset of Withdrawal Bleeding Episodes at Cycle 1	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.	At cycle 1 (28 days per cycle)
Onset of Withdrawal Bleeding Episodes at Cycle 3	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.	At cycle 3 (28 days per cycle)
Percentage of Participants With Intracyclic Bleeding at Cycle 1	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.	At cycle 1 (28 days per cycle)
Percentage of Participants With Intracyclic Bleeding at Cycle 3	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.	At cycle 3 (28 days per cycle)
Number of Intracyclic Bleeding Episodes at Cycle 1	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.	At cycle 1 (28 days per cycle)
Number of Intracyclic Bleeding Episodes at Cycle 3	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.	At cycle 3 (28 days per cycle)
Maximum Length of Intracyclic Bleeding Episodes at Cycle 1	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.	At cycle 1 (28 days per cycle)
Maximum Length of Intracyclic Bleeding Episodes at Cycle 3	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.	At cycle 3 (28 days per cycle)
Number of Intracyclic Bleeding Days at Cycle 1	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. The total number of days during intracyclic bleeding episodes was counted.	At cycle 1 (28 days per cycle)
Number of Intracyclic Bleeding Days at Cycle 3	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. The total number of days during intracyclic bleeding episodes was counted.	At cycle 3 (28 days per cycle)
Percentage of Participants With Maximum Intensity of Intracyclic Bleeding Episodes at Cycle 1	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. Intensity could be described as spotting, light, normal or heavy.	At cycle 1 (28 days per cycle)
Percentage of Participants With Maximum Intensity of Intracyclic Bleeding Episodes at Cycle 3	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. Intensity could be described as spotting, light, normal or heavy.	At cycle 3 (28 days per cycle)
Percentage of Participants Missing Time From Work Due to Dysmenorrheic Pain at Screening	The investigator was asked to interview the participant and record the number of missed hours/days from work due to dysmenorrheic pain in the previous menstrual cycle.	At screening (28 days)
Percentage of Participants Missing Time From Work Due to Dysmenorrheic Pain at Baseline Cycle	The investigator was asked to interview the participant and record the number of missed hours/days from work due to dysmenorrheic pain in the previous menstrual cycle.	At Baseline (28 days per cycle)
Percentage of Participants Missing Time From Work Due to Dysmenorrheic Pain at Cycle 2	The investigator was asked to interview the participant and record the number of missed hours/days from work due to dysmenorrheic pain in the previous menstrual cycle.	At cycle 2 (28 days per cycle)
Percentage of Participants Missing Time From Work Due to Dysmenorrheic Pain at Final Examination	The investigator was asked to interview the participant and record the number of missed hours/days from work due to dysmenorrheic pain in the previous menstrual cycle.	At final examination (28 days)
Own Costs of Physiotherapy Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire	The participants 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.	At screening (average over 3 months before screening)
Own Costs of Pain Medication Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire	The participants 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.	At screening (average over 3 months before screening)
Own Costs of Vitamins Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire	The participants 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.	At screening (average over 3 months before screening)
Own Costs of Massages Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire	The participants 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.	At screening (average over 3 months before screening)
Own Costs of Acupuncture Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire	The participants 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.	At screening (average over 3 months before screening)
Own Costs of Medical Counseling Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire	The participants were asked to complete a resource use questionnaire indicating their own costs of medical counseling per treatment of dysmenorrheic pain. Costs were converted to U.S. dollars.	At screening (average over 3 months before screening)
Own Costs of Alternative Medicine Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire	The participants were asked to complete a resource use questionnaire indicating their own costs of alternative medicine per treatment of dysmenorrheic pain. Costs were converted to U.S. dollars.	At screening (average over 3 months before screening)
Own Costs of Herbs/Teas Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire	The participants 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.	At screening (average over 3 months before screening)
Other Own Costs Per Treatment Converted to U.S. Dollars as Measured by Resource Use Questionnaire	The participants 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.	At screening (average over 3 months before screening)
Participants With Improvement in the Investigators' Assessment in the Clinical Global Impression	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 participants' improvement during the course of the study.	At cycle 2 (28 days per cycle)
Participants With Improvement in Participants' Assessment in the Clinical Global Impression	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. Participants were asked to rate their improvement during the course of the study.	At cycle 2 (28 days per cycle)
Physical Functioning as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle	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 participants 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)	At baseline cycle (28 days per cycle)
Physical Functioning as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination	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 participants 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)	at final examination (28 days)
Social Functioning as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle	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 participants 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)	At baseline cycle (28 days per cycle)
Social Functioning as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination	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 participants 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)	At final examination (28 days)
Mental Health as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle	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 participants 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)	At baseline cycle (28 days per cycle)
Mental Health as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination	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 participants 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)	At final examination (28 days)
Vitality as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle	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 participants 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)	At baseline cycle (28 days per cycle)
Vitality as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination	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 participants 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)	At final examination (28 days)
General Health as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle	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 participants 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)	At baseline cycle (28 days per cycle)
General Health as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination	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 participants 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)	At final examination (28 days)
Role Physical as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle	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 participants 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)	At baseline cycle (28 days per cycle)
Role Physical as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination	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 participants 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)	At final examination (28 days)
Role Emotional as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle	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 participants 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)	At baseline cycle (28 days per cycle)
Role Emotional as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination	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 participants 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)	At final examination (28 days)
Bodily Pain as Measured by General Health and Well-being Questionnaire SF-36 at Baseline Cycle	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 participants 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)	At baseline cycle (28 days per cycle)
Bodily Pain as Measured by General Health and Well-being Questionnaire SF-36 at Final Examination	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 participants 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)	At final examination (28 days)

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Petraglia F, Parke S, Serrani M, Mellinger U, Romer T. Estradiol valerate plus dienogest versus ethinylestradiol plus levonorgestrel for the treatment of primary dysmenorrhea. Int J Gynaecol Obstet. 2014 Jun;125(3):270-4. doi: 10.1016/j.ijgo.2013.11.017. Epub 2014 Mar 11.

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (ACTUAL): November 1, 2010
• Study Completion (ACTUAL): November 1, 2010

Study Registration Dates

• First Submitted: April 24, 2009
• First Submitted That Met QC Criteria: May 28, 2009
• First Posted (ESTIMATE): May 29, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): August 24, 2015
• Last Update Submitted That Met QC Criteria: August 6, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Primary Dysmenorrhea; Oral Contraception
• Additional Relevant MeSH Terms: Pathologic Processes; Pain; Neurologic Manifestations; Menstruation Disturbances; Pelvic Pain; Dysmenorrhea; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Estrogens; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Contraceptive Agents, Male; Levonorgestrel; Estradiol; Ethinyl Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate; Dienogest
• Other Study ID Numbers: 91781; 2008-005625-11 (EUDRACT_NUMBER); 312042 (OTHER: Bayer)