Safety Study of Ethinylestradiol/Drospirenone in Dysmenorrhea

Dysmenorrhea Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00461305
• Other study ID #: 91616
• Secondary ID: 310284
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: April 17, 2007
• Last updated: January 22, 2013
• Start date: February 2007
• Est. completion date: August 2009

Study information

• Verified date: January 2013
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 420
• Est. completion date: August 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dysmenorrhea

Intervention

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)
• 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)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Intracyclic Bleeding at Cycle 6	Intracyclic bleedings were defined as bleedings while a participant takes active tablets.	Up to Cycle 6 (168 days) with 28 days per cycle	No
Secondary	Number of Participants With a Change in Total Dysmenorrhea Score From Baseline to Cycle 6	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.	From baseline up to Cycle 6 (168 days) with 28 days per cycle	No
Secondary	Number of Participants With a Change in Total Dysmenorrhea Score From Baseline to Cycle 13	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.	From baseline up to Cycle 13 (364 days) with 28 days per cycle	No
Secondary	Distribution of Total Dysmenorrhea Score at Cycle 6	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.	Up to Cycle 6 (168 days) with 28 days per cycle	No
Secondary	Distribution of Total Dysmenorrhea Score at Cycle 13	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.	Up to Cycle 13 (364 days) with 28 days per cycle	No
Secondary	Distribution of Severity of Lower Abdominal Pain During Menstruation at Cycle 6	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).	Up to Cycle 6 (168 days) with 28 days per cycle	No
Secondary	Distribution of Severity of Lower Abdominal Pain During Menstruation at Cycle 13	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).	Up to Cycle 13 (364 days) with 28 days per cycle	No
Secondary	Distribution of Severity of Lumbago During Menstruation at Cycle 6	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).	Up to Cycle 6 (168 days) with 28 days per cycle	No
Secondary	Distribution of Severity of Lumbago During Menstruation at Cycle 13	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).	Up to Cycle 13 (364 days) with 28 days per cycle	No
Secondary	Distribution of Severity of Headache During Menstruation at Cycle 6	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).	Up to Cycle 6 (168 days) with 28 days per cycle	No
Secondary	Distribution of Severity of Headache During Menstruation at Cycle 13	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).	Up to Cycle 13 (364 days) with 28 days per cycle	No
Secondary	Distribution of Severity of Nausea or Vomiting During Menstruation at Cycle 6	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).	Up to Cycle 6 (168 days) with 28 days per cycle	No
Secondary	Distribution of Severity of Nausea or Vomiting During Menstruation at Cycle 13	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).	Up to Cycle 13 (364 days) with 28 days per cycle	No
Secondary	Number of Participants With a Total Pelvic Pain Score of 0 up to 6 at Times Other Than During Menstruation at Cycle 6	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.	Up to Cycle 6 (168 days) with 28 days per cycle	No
Secondary	Number of Participants With a Total Pelvic Pain Score of 0 up to 6 at Times Other Than During Menstruation at Cycle 13	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.	Up to Cycle 13 (364 days) with 28 days per cycle	No
Secondary	Change in Visual Analogue Scale (VAS) for Dysmenorrhea at Times Other Than During Menstruation From Baseline to Cycle 6	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).	From baseline up to Cycle 6 (168 days) with 28 days per cycle	No
Secondary	Change in Visual Analogue Scale (VAS) for Dysmenorrhea at Times Other Than During Menstruation From Baseline to Cycle 13	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).	From baseline up to Cycle 13 (364 days) with 28 days per cycle	No
Secondary	Change in Visual Analogue Scale (VAS) for Pelvic Pain at Times Other Than During Menstruation From Baseline to Cycle 6	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).	From baseline up to Cycle 6 (168 days) with 28 days per cycle	No
Secondary	Change in Visual Analogue Scale (VAS) for Pelvic Pain at Times Other Than During Menstruation From Baseline to Cycle 13	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).	From baseline up to Cycle 13 (364 days) with 28 days per cycle	No
Secondary	Number of Any Bleeding Episodes From Cycle 1 to Cycle 6	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).	Up to Cycle 6 (168 days) with 28 days per cycle	No
Secondary	Number of Any Bleeding Episodes From Cycle 1 to Cycle 13	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).	Up to Cycle 13 (364 days) with 28 days per cycle	No
Secondary	Number of Any Bleeding Days From Cycle 1 to Cycle 6	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).	Up to Cycle 6 (168 days) with 28 days per cycle	No
Secondary	Number of Any Bleeding Days From Cycle 1 to Cycle 13	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).	Up to Cycle 13 (364 days) with 28 days per cycle	No
Secondary	Number of Participants With Intracyclic Bleeding From Cycle 1 to Cycle 6	Intracyclic bleedings were defined as bleedings while a participant takes active tablets.	Up to Cycle 6 (168 days) with 28 days per cycle	No
Secondary	Number of Participants With Intracyclic Bleeding From Cycle 1 to Cycle 13	Intracyclic bleedings were defined as bleedings while a participant takes active tablets.	Up to Cycle 13 (364 days) with 28 days per cycle	No
Secondary	Number of Participants With Withdrawal Bleeding From Cycle 1 to Cycle 6	Withdrawal bleedings were defined as bleedings while a participant takes placebo tablets.	Up to Cycle 6 (168 days) with 28 days per cycle	No
Secondary	Number of Participants With Withdrawal Bleeding From Cycle 1 to Cycle 13	Withdrawal bleedings were defined as bleedings while a participant takes placebo tablets.	Up to Cycle 13 (364 days) with 28 days per cycle	No
Secondary	Percentage of Participants With Non-heavy Intracyclic Bleeding From Cycle 1 to Cycle 6	Non-heavy bleeding was defined as those other than heavy bleeding (i.e. spotting, light, or normal bleeding).	Up to Cycle 6 (168 days) with 28 days per cycle	No
Secondary	Percentage of Participants With Non-heavy Intracyclic Bleeding From Cycle 1 to Cycle 13	Non-heavy bleeding was defined as those other than heavy bleeding (i.e. spotting, light, or normal bleeding).	Up to Cycle 13 (364 days) with 28 days per cycle	No
Secondary	Percentage of Participants With Non-heavy Withdrawal Bleeding From Cycle 1 to Cycle 6	Non-heavy bleeding was defined as those other than heavy bleeding (i.e. spotting, light, or normal bleeding).	Up to Cycle 6 (168 days) with 28 days per cycle	No
Secondary	Percentage of Participants With Non-heavy Withdrawal Bleeding From Cycle 1 to Cycle 13	Non-heavy bleeding was defined as those other than heavy bleeding (i.e. spotting, light, or normal bleeding).	Up to Cycle 13 (364 days) with 28 days per cycle	No
Secondary	Change in Serum Carbohydrate Antigen-125 (CA-125) From Baseline to Cycle 6	CA125 is a laboratory parameter giving an indication of having tumor, whose elevated levels that were defined by a lab suggest a potential tumor.	From baseline up to Cycle 6 (168 days) with 28 days per cycle	No
Secondary	Change in Serum CA-125 From Baseline to Cycle 13	CA125 is a laboratory parameter giving an indication of having tumor, whose elevated levels that were defined by a lab suggest a potential tumor.	From baseline up to Cycle 13 (364 days) with 28 days per cycle	No
Secondary	Change in Serum C-reactive Protein (CRP) From Baseline to Cycle 6	CRP is a laboratory parameter giving an indication of inflammation, whose elevated level suggests a potential inflammation.	From baseline up to Cycle 6 (168 days) with 28 days per cycle	No
Secondary	Change in Serum CRP From Baseline to Cycle 13	CRP is a laboratory parameter giving an indication of inflammation, whose elevated level suggests a potential inflammation.	From baseline up to Cycle 13 (364 days) with 28 days per cycle	No

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