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Safety Study of Ethinylestradiol/Drospirenone in Dysmenorrhea

This study has been completed.
Sponsor:
Information provided by:
Bayer
ClinicalTrials.gov Identifier:
NCT00461305
First received: April 17, 2007
Last updated: January 22, 2013
Last verified: January 2013

April 17, 2007
January 22, 2013
February 2007
January 2009   (final data collection date for primary outcome measure)
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.
Incidence rate of intracyclic bleeding in 6th cycle
Complete list of historical versions of study NCT00461305 on ClinicalTrials.gov Archive Site
  • 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.
  • Change in the total dysmenorrheal score
  • Changes over time in total dysmenorrheal score
  • Change in severity of lower abdominal pain, lumbago, headache, and nausea or vomiting during menstruation
  • Change of pelvic pain score at pelvic pain score at times other than during menstruation periods
  • Change of VAS for dysmenorrhea and pelvic pain at pelvic pain score at times other than during menstruation periods
  • Status of vaginal bleeding
Not Provided
Not Provided
 
Safety Study of Ethinylestradiol/Drospirenone in Dysmenorrhea
A Multicenter, Single-blind, Randomized Study, to Investigate Efficacy of Ethinylestradiol for Intracyclic Bleeding Profile During 24 Weeks (6 Cycles) by Oral Administration of Drospirenone 3 mg/Ethinylestradiol 20 µg and Drospirenone 3 mg/ Ethinylestradiol 30 µg in Patients With Dysmenorrheal and to Investigate the Long Term Safety Oral Administration of Drospirenone 3 mg/Ethinylestradiol 20 µg Administered for 52 Weeks (13 Cycles)

The purpose of this study is to investigate efficacy of ethinylestradiol for intracyclic bleeding profile in patients with dysmenorrhea and to investigate the long term safety

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Dysmenorrhea
  • Drug: DRSP 3 mg/EE 20 µg (13 cycles)
    1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 µg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle; treatment duration 52 weeks (13 cycles)
  • Drug: DRSP 3 mg/EE 30 µg (6 cycles)
    1 tablet per day Drospirenone 3 mg/Ethinylestradiol 30 µg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle; treatment duration 24 weeks (6 cycles)
  • Experimental: DRSP 3 mg/EE 20 µg (13 cycles)
    1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 µg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle; treatment duration 52 weeks (13 cycles)
    Intervention: Drug: DRSP 3 mg/EE 20 µg (13 cycles)
  • Experimental: DRSP 3 mg/EE 30 µg (6 cycles)
    1 tablet per day Drospirenone 3 mg/Ethinylestradiol 30 µg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle; treatment duration 24 weeks (6 cycles)
    Intervention: Drug: DRSP 3 mg/EE 30 µg (6 cycles)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
420
August 2009
January 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients aged 20 years or older at obtaining informed consent
  • Patients having the normal menstrual cycle (25 to 38 days) in the latest two menses before the final enrollment
  • Patients having a total dysmenorrheal score of at least 3 points in twice of the latest menstruation before the final enrollment

Exclusion Criteria:

  • Patients with ovarian chocolate cysts
  • Patients with fibroid needed to be treated
  • Patients with estrogen-dependent tumors and patients with cervical cancer or suspected cervical cancer
  • Patients with undiagnosed abnormal vaginal bleeding
  • Patients with thrombophlebitis, pulmonary embolism, cerebrovascular disease, or coronary artery disease or a history of those diseases
  • Patients aged 35 years or older who smoke at least 15 cigarettes per day
  • Patients with migraine accompanied by prodromata
  • Patients with pulmonary hypertension or valvular heart disease
  • Patients who are regularly taking nutritional products that contain St. John's Wort
  • Patients who underwent surgical treatment for endometriosis within 2 months prior to screening
  • Patients who may need to regularly use analgesics for therapeutic objectives other than relief from the pain of dysmenorrhea during this study (occasional use permitted)
Female
20 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Japan
 
NCT00461305
91616, 310284
No
Therapeutic Area Head, Bayer Yakuhin, Ltd.
Bayer
Not Provided
Study Director: Bayer Study Director Bayer
Bayer
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP