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
  Purpose

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


Condition Intervention Phase
Dysmenorrhea
Drug: DRSP 3 mg/EE 20 µg (13 cycles)
Drug: DRSP 3 mg/EE 30 µg (6 cycles)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 420
Study Start Date: February 2007
Study Completion Date: August 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
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)
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)
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)

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00461305

Locations
Japan
Nagoya, Aichi, Japan, 460-0007
Nagoya, Aichi, Japan, 464-0066
Nagoya, Aichi, Japan, 460-0011
Maebashi, Gunma, Japan, 371-0024
Takasaki, Gunma, Japan, 370-0883
Kobe, Hyogo, Japan, 650-0021
Nishinomiya, Hyogo, Japan, 663-8204
Yamato, Kanagawa, Japan, 242-0007
Yokohama, Kanagawa, Japan, 231-0861
Sendai, Miyagi, Japan, 981-0933
Sendai, Miyagi, Japan, 984-0042
Sendai, Miyagi, Japan, 980-0021
Toyonaka, Osaka, Japan, 560-0022
Chuo-ku, Tokyo, Japan, 104-0061
Hachioji, Tokyo, Japan, 192-0046
Machida, Tokyo, Japan, 194-0022
Musashino, Tokyo, Japan, 180-0003
Ota-ku, Tokyo, Japan, 144-0052
Setagaya-ku, Tokyo, Japan, 157-0066
Setagaya-ku, Tokyo, Japan, 156-0042
Shibuya-ku, Tokyo, Japan, 150-0013
Shinagawa-ku, Tokyo, Japan, 140-0013
Suginami-ku, Tokyo, Japan, 167-0051
Toshima-ku, Tokyo, Japan, 171-0021
Osaka, Japan, 530-0013
Osaka, Japan, 534-0014
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Therapeutic Area Head, Bayer Yakuhin, Ltd.
ClinicalTrials.gov Identifier: NCT00461305     History of Changes
Other Study ID Numbers: 91616, 310284
Study First Received: April 17, 2007
Results First Received: September 10, 2010
Last Updated: January 22, 2013
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Bayer:
Dysmenorrhea
Intracyclic bleeding
Drospirenone (DRSP)
Ethinylestradiol

Additional relevant MeSH terms:
Dysmenorrhea
Menstruation Disturbances
Pathologic Processes
Pelvic Pain
Pain
Signs and Symptoms
Ethinyl Estradiol
Drospirenone
Drospirenone and ethinyl estradiol combination
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Aldosterone Antagonists
Hormone Antagonists
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014