Study of a 4-phasic Oral Contraceptive for the Treatment of Heavy Menstrual Bleeding

A Multicenter, Double-blind, Randomized, Parallel-group, Placebo-controlled, 7 Cycle Duration (196 Days), Phase 3 Study to Investigate the Efficacy and Safety of Oral Estradiol Valerate / Dienogest Tablets for the Treatment of Heavy Menstrual Bleeding

To evaluate efficacy and safety of a combined oral contraceptive of estradiol valerate and dienogest in the treatment of heavy menstrual bleeding

Study Overview

• Status: Completed
• Conditions: Metrorrhagia
• Intervention / Treatment: Drug: EV/DNG (Qlaira, Natazia, BAY86-5027); Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 339
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100044
  • Beijing, China, 100730
  • Beijing, China, 100026
  • Beijing, China, 100034
  • Changchun, China
  • Chongqing, China, 400010
  • Qingdao, China, 266071
  • Shanghai, China, 200030
  • Shanghai, China, 2100129
  • Tianjin, China, 300211
  • Tianjin, China, 300193
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
  • Guangxi
    • Nanning, Guangxi, China, 530021
  • Hebei
    • Shijiazhuang, Hebei, China, 050051
  • Hubei
    • Wuhan, Hubei, China, 430032
    • Wuhan, Hubei, China, 430030
  • Hunan
    • Changsha, Hunan, China, 410013
    • Hengyang, Hunan, China, 421001
  • Liaoning
    • Dalian, Liaoning, China, 116011
    • Shenyang, Liaoning, China, 110004
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
  • Shandong
    • Jinan, Shandong, China, 250012
  • Sichuan
    • Chengdu, Sichuan, China, 610041
    • Chengdu, Sichuan, China, 610072
• Philippines
  • Manila, Philippines
  • Quezon City, Philippines
• Russian Federation
  • Irkutsk, Russian Federation, 664003
  • Ivanovo, Russian Federation, 153045
  • Krasnodar, Russian Federation, 350012
  • Moscow, Russian Federation, 117049
  • Moscow, Russian Federation, 117415
  • St. Petersburg, Russian Federation, 194354
  • St. Petersburg, Russian Federation, 199034
• Singapore
  • Singapore, Singapore, 169608
  • Singapore, Singapore, 229899
• Taiwan
  • Taichung, Taiwan, 40705
  • Tainan, Taiwan
  • Taipei, Taiwan, 100
  • Taipei, Taiwan, 11217
• Thailand
  • Bangkok, Thailand, 10700
  • Bangkok, Thailand, 10330

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women 18 years or older in generally good health with a diagnosis of heavy menstrual bleeding without organic pathology, requesting contraception
• Willingness to use barrier contraception (e.g., condoms) from screening to study completion
• Willingness to use and collect sanitary protection (pads and tampons) provided by the sponsor and compatible with the alkaline hematin test throughout study completion

Exclusion Criteria:

• Current diagnosis of organic uterine bleeding
• History of endometrial ablation, or dilatation and curettage within 2 months of Visit 1.
• Clinically significant pelvic findings (whether or not confirmed by transvaginal ultrasound [TVU]).
• Clinically significant abnormal results of breast examination (breast palpation).
• Positive pregnancy test at Visit 1
• Less than three months since delivery, abortion, or lactation before to start Visit 1
• Other contraceptive methods
• Any disease or condition that may worsen under hormonal treatment
• Smokers over the age of 35
• Body mass index >32

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1	Drug: EV/DNG (Qlaira, Natazia, BAY86-5027); 2 days of 3 mg estradiol valerate (EV);5 days of 2 mg EV + 2 mg dienogest (DNG);17 days of 2 mg EV + 3 mg DNG;2 days of 1 mg EV;2 days of placebo. A blister card consists of 28 pills, taken orally once a day for 7 cycles of 28 days each.
Placebo Comparator: Arm 2	Drug: placebo; Matching placebo to be taken orally daily for 7 cycles of 28 days each.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Absolute change in Menstrual Blood Loss (MBL) at baseline and 90 days	90 day baseline period and 90 days during treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with successful treatment	Successful treatment is defined as no bleeding episode with MBL of 80 mL or more and a decrease to a value </=50% of MBL compared to 90 day run-in period	90 days during treatment phase
Percent change of MBL at baseline and 90 day period during treatment phase		Baseline and 90 days during treatment phase
Absolute change of average MBL at baseline and up to cycle 7 (one cycle = 28 days)		Baseline and cycle 1, cycle 2, cycle 3, cycle 4, cycle 5, cycle 6, cycle 7
Proportion of subjects with improvement in the investigator's global assessment scale on Day 84	Investigator's global assessment scale: 0 = not assessed; 1 = very much improved; 2 = much improved; 3 = improved; 4 = no change; 5 = worse; 6 = much worse; 7 = very much worse; Improvement is defined as the assessment score = 1, 2, or 3.	Treatment day 84
Proportion of subjects with improvement in the investigator's global assessment scale on Day 196	Investigator's global assessment scale: 0 = not assessed; 1 = very much improved; 2 = much improved; 3 = improved; 4 = no change; 5 = worse; 6 = much worse; 7 = very much worse; Improvement is defined as the assessment score = 1, 2, or 3.	Treatment day 196
Proportion of subjects with improvement in the subject's global assessment scale on Day 84	Subject's global assessment scale: 0 = not assessed; 1 = very much improved; 2 = much improved; 3 = improved; 4 = no change; 5 = worse; 6 = much worse; 7 = very much worse; Improvement is defined as the assessment score = 1, 2, or 3.	Treatment day 84
Proportion of subjects with improvement in the subject's global assessment scale on Day 196	Subject's global assessment scale: 0 = not assessed; 1 = very much improved; 2 = much improved; 3 = improved; 4 = no change; 5 = worse; 6 = much worse; 7 = very much worse; Improvement is defined as the assessment score = 1, 2, or 3.	Treatment day 196
Number of participants with adverse events as a measure of safety and tolerability		Up to 12 months

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: June 20, 2012
• First Submitted That Met QC Criteria: July 10, 2012
• First Posted (Estimate): July 12, 2012

Study Record Updates

• Last Update Posted (Estimate): July 10, 2015
• Last Update Submitted That Met QC Criteria: July 8, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Oral contraceptive; Dienogest; Heavy Menstrual Bleeding; Estradiol valerate
• Additional Relevant MeSH Terms: Pathologic Processes; Uterine Diseases; Menstruation Disturbances; Uterine Hemorrhage; Hemorrhage; Metrorrhagia; Menorrhagia
• Other Study ID Numbers: 91774; X311965 (Other Identifier: Company Internal)