Safety Study of Ethinylestradiol/Drospirenone in Dysmenorrhea

• Number of Participants With Intracyclic Bleeding at Cycle 6 [ Time Frame: Up to Cycle 6 (168 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Intracyclic bleedings were defined as bleedings while a participant takes active tablets.
  
  

• Number of Participants With a Change in Total Dysmenorrhea Score From Baseline to Cycle 6 [ Time Frame: From baseline up to Cycle 6 (168 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Total dysmenorrheal score was defined as sum of 2 sub-scores: severity of dysmenorrhea (none: 0, mild: 1, moderate: 2, severe: 3) and use of analgesics (none: 0, mild: 1, moderate: 2, severe: 3). Note: used with permission of Nobelpharma Co., Ltd. from the phase 3 clinical study protocol of IKH-01 in dysmenorrhea (associated with endometriosis) (Nobelpharma Co., Ltd.). Changed total dysmenorrheal scores: -6 to -1 mean improvement, 1 to 6 mean worsening, 0 means no change.
  
  
• Number of Participants With a Change in Total Dysmenorrhea Score From Baseline to Cycle 13 [ Time Frame: From baseline up to Cycle 13 (364 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Total dysmenorrheal score was defined as sum of 2 sub-scores: severity of dysmenorrhea (none: 0, mild: 1, moderate: 2, severe: 3) and use of analgesics (none: 0, mild: 1, moderate: 2, severe: 3). Note: used with permission of Nobelpharma Co., Ltd. from the phase 3 clinical study protocol of IKH-01 in dysmenorrhea (associated with endometriosis) (Nobelpharma Co., Ltd.). Changed total dysmenorrheal scores: -6 to -1 mean improvement, 1 to 6 mean worsening, 0 means no change.
  
  
• Distribution of Total Dysmenorrhea Score at Cycle 6 [ Time Frame: Up to Cycle 6 (168 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Total dysmenorrhea score was defined as sum of 2 sub-scores: severity of dysmenorrhea and use of analgesics. Higher score means it is more severe. 0=None, 6=Severest.
  
  
• Distribution of Total Dysmenorrhea Score at Cycle 13 [ Time Frame: Up to Cycle 13 (364 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Total dysmenorrhea score was defined as sum of 2 sub-scores: severity of dysmenorrhea and use of analgesics. Higher score means it is more severe. 0=None, 6=Severest.
  
  
• Distribution of Severity of Lower Abdominal Pain During Menstruation at Cycle 6 [ Time Frame: Up to Cycle 6 (168 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Severity of lower abdominal pain during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).
  
  
• Distribution of Severity of Lower Abdominal Pain During Menstruation at Cycle 13 [ Time Frame: Up to Cycle 13 (364 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Severity of lower abdominal pain during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).
  
  
• Distribution of Severity of Lumbago During Menstruation at Cycle 6 [ Time Frame: Up to Cycle 6 (168 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Severity of lumbago during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).
  
  
• Distribution of Severity of Lumbago During Menstruation at Cycle 13 [ Time Frame: Up to Cycle 13 (364 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Severity of lumbago during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).
  
  
• Distribution of Severity of Headache During Menstruation at Cycle 6 [ Time Frame: Up to Cycle 6 (168 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Severity of headache during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).
  
  
• Distribution of Severity of Headache During Menstruation at Cycle 13 [ Time Frame: Up to Cycle 13 (364 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Severity of headache during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).
  
  
• Distribution of Severity of Nausea or Vomiting During Menstruation at Cycle 6 [ Time Frame: Up to Cycle 6 (168 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Severity of nausea or vomiting during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).
  
  
• Distribution of Severity of Nausea or Vomiting During Menstruation at Cycle 13 [ Time Frame: Up to Cycle 13 (364 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Severity of nausea or vomiting during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).
  
  
• Number of Participants With a Total Pelvic Pain Score of 0 up to 6 at Times Other Than During Menstruation at Cycle 6 [ Time Frame: Up to Cycle 6 (168 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Total pelvic pain score was defined as sum of 2 sub-scores: severity of dysmenorrhea and use of analgesics. Higher score means it is more severe. 0=None, 6=Severest.
  
  
• Number of Participants With a Total Pelvic Pain Score of 0 up to 6 at Times Other Than During Menstruation at Cycle 13 [ Time Frame: Up to Cycle 13 (364 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Total pelvic pain score was defined as sum of 2 sub-scores: severity of dysmenorrhea and use of analgesics. Higher score means it is more severe. 0=None, 6=Severest.
  
  
• Change in Visual Analogue Scale (VAS) for Dysmenorrhea at Times Other Than During Menstruation From Baseline to Cycle 6 [ Time Frame: From baseline up to Cycle 6 (168 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  VAS is an unmarked scale on a line 100 mm in length, indicating from 0 mm (no pain) to 100 mm (worst pain a participant has ever experienced).
  
  
• Change in Visual Analogue Scale (VAS) for Dysmenorrhea at Times Other Than During Menstruation From Baseline to Cycle 13 [ Time Frame: From baseline up to Cycle 13 (364 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  VAS is an unmarked scale on a line 100 mm in length, indicating from 0 mm (no pain) to 100 mm (worst pain a participant has ever experienced).
  
  
• Change in Visual Analogue Scale (VAS) for Pelvic Pain at Times Other Than During Menstruation From Baseline to Cycle 6 [ Time Frame: From baseline up to Cycle 6 (168 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  VAS is an unmarked scale on a line 100 mm in length, indicating from 0 mm (no pain) to 100 mm (worst pain a participant has ever experienced).
  
  
• Change in Visual Analogue Scale (VAS) for Pelvic Pain at Times Other Than During Menstruation From Baseline to Cycle 13 [ Time Frame: From baseline up to Cycle 13 (364 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  VAS is an unmarked scale on a line 100 mm in length, indicating from 0 mm (no pain) to 100 mm (worst pain a participant has ever experienced).
  
  
• Number of Any Bleeding Episodes From Cycle 1 to Cycle 6 [ Time Frame: Up to Cycle 6 (168 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Vaginal bleeding was rated as none, spotting, light, normal, or heavy based on the participant's experience. A reference period is about 3 cycles (90 days): reference period 1 is from Cycle 1 to Cycle 3 (the 1st 90 days), reference period 2 is from Cycle 4 to Cycle 6 (the 2nd 90 days).
  
  
• Number of Any Bleeding Episodes From Cycle 1 to Cycle 13 [ Time Frame: Up to Cycle 13 (364 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Vaginal bleeding was rated as none, spotting, light, normal, or heavy based on the participant's experience. A reference period is about 3 cycles (90 days): reference period 1 is from Cycle 1 to Cycle 3 (the 1st 90 days), reference period 2 is from Cycle 4 to Cycle 6 (the 2nd 90 days), reference period 3 is from Cycle 7 to Cycle 9 (the 3rd 90 days), reference period 4 is from Cycle 10 to Cycle 12 (the 4th 90 days).
  
  
• Number of Any Bleeding Days From Cycle 1 to Cycle 6 [ Time Frame: Up to Cycle 6 (168 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Vaginal bleeding was rated as none, spotting, light, normal, or heavy based on the participant's experience. A reference period is about 3 cycles (90 days): reference period 1 is from Cycle 1 to Cycle 3 (the 1st 90 days), reference period 2 is from Cycle 4 to Cycle 6 (the 2nd 90 days).
  
  
• Number of Any Bleeding Days From Cycle 1 to Cycle 13 [ Time Frame: Up to Cycle 13 (364 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Vaginal bleeding was rated as none, spotting, light, normal, or heavy based on the participant's experience. A reference period is about 3 cycles (90 days): reference period 1 is from Cycle 1 to Cycle 4 (the 1st 90 days), reference period 2 is from Cycle 4 to Cycle 6 (the 2nd 90 days), reference period 3 is from Cycle 7 to Cycle 9 (the 3rd 90 days), reference period 4 is from Cycle 10 to Cycle 12 (the 4th 90 days).
  
  
• Number of Participants With Intracyclic Bleeding From Cycle 1 to Cycle 6 [ Time Frame: Up to Cycle 6 (168 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Intracyclic bleedings were defined as bleedings while a participant takes active tablets.
  
  
• Number of Participants With Intracyclic Bleeding From Cycle 1 to Cycle 13 [ Time Frame: Up to Cycle 13 (364 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Intracyclic bleedings were defined as bleedings while a participant takes active tablets.
  
  
• Number of Participants With Withdrawal Bleeding From Cycle 1 to Cycle 6 [ Time Frame: Up to Cycle 6 (168 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Withdrawal bleedings were defined as bleedings while a participant takes placebo tablets.
  
  
• Number of Participants With Withdrawal Bleeding From Cycle 1 to Cycle 13 [ Time Frame: Up to Cycle 13 (364 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Withdrawal bleedings were defined as bleedings while a participant takes placebo tablets.
  
  
• Percentage of Participants With Non-heavy Intracyclic Bleeding From Cycle 1 to Cycle 6 [ Time Frame: Up to Cycle 6 (168 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Non-heavy bleeding was defined as those other than heavy bleeding (i.e. spotting, light, or normal bleeding).
  
  
• Percentage of Participants With Non-heavy Intracyclic Bleeding From Cycle 1 to Cycle 13 [ Time Frame: Up to Cycle 13 (364 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Non-heavy bleeding was defined as those other than heavy bleeding (i.e. spotting, light, or normal bleeding).
  
  
• Percentage of Participants With Non-heavy Withdrawal Bleeding From Cycle 1 to Cycle 6 [ Time Frame: Up to Cycle 6 (168 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Non-heavy bleeding was defined as those other than heavy bleeding (i.e. spotting, light, or normal bleeding).
  
  
• Percentage of Participants With Non-heavy Withdrawal Bleeding From Cycle 1 to Cycle 13 [ Time Frame: Up to Cycle 13 (364 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  Non-heavy bleeding was defined as those other than heavy bleeding (i.e. spotting, light, or normal bleeding).
  
  
• Change in Serum Carbohydrate Antigen-125 (CA-125) From Baseline to Cycle 6 [ Time Frame: From baseline up to Cycle 6 (168 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  CA125 is a laboratory parameter giving an indication of having tumor, whose elevated levels that were defined by a lab suggest a potential tumor.
  
  
• Change in Serum CA-125 From Baseline to Cycle 13 [ Time Frame: From baseline up to Cycle 13 (364 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  CA125 is a laboratory parameter giving an indication of having tumor, whose elevated levels that were defined by a lab suggest a potential tumor.
  
  
• Change in Serum C-reactive Protein (CRP) From Baseline to Cycle 6 [ Time Frame: From baseline up to Cycle 6 (168 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  CRP is a laboratory parameter giving an indication of inflammation, whose elevated level suggests a potential inflammation.
  
  
• Change in Serum CRP From Baseline to Cycle 13 [ Time Frame: From baseline up to Cycle 13 (364 days) with 28 days per cycle ] [ Designated as safety issue: No ]
  CRP is a laboratory parameter giving an indication of inflammation, whose elevated level suggests a potential inflammation.
  
  

The "drospirenone 3 mg/ethinylestradiol 20 μg (13 cycles)" group is to be treated by oral administration for 52 weeks, 13 cycles. The "drospirenone 3 mg/ethinylestradiol 30 μg (6 cycles)" group is to be treated by oral administration for 24 weeks, 6 cycles.

The trial is sponsored by Bayer Yakuhin, Ltd.