Study in Women With Idiopathic Menorrhagia to Determine the Reduction in Menstrual Blood Loss (MBL) After Treatment With the Levonorgestrel-releasing Intrauterine System (IUS)

A Multicenter, Randomized, Open Label, Parallel Group, Active Control Study to Evaluate the Efficacy and Safety of LNG IUS (Mirena®) as Compared to Medroxyprogesterone Acetate During 6 Cycles of Treatment in Patients With Idiopathic Menorrhagia

The purpose of this study is to determine whether the levonorgestrel-releasing intrauterine system is effective in decreasing menstrual blood loss.

Study Overview

• Status: Completed
• Conditions: Menorrhagia
• Intervention / Treatment: Drug: Levonorgestrel IUS (Mirena, BAY86-5028); Drug: Medroxyprogesterone acetate

Detailed Description

Acronyms in the Adverse Event Section:

• IUCD Intrauterine Contraceptive Device
• MedDRA Medical Dictionary for Regulatory Activities

This study has previously been posted by Berlex, Inc. and Schering AG, Germany. Berlex, Inc. has been renamed to Bayer HealthCare Pharmaceuticals, Inc., Schering AG Germany has been renamed to Bayer HealthCare AG, Germany.

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1425
  • Buenos Aires, Argentina, C1181ACH
• Brazil
  • Parana
    • Curitiba, Parana, Brazil, 80030-220
  • Sao Paulo
    • Campinas, Sao Paulo, Brazil, 13083-970
• Canada
  • Quebec, Canada, G1S 2L6
  • New Brunswick
    • Bathurst, New Brunswick, Canada, E2A 4X7
  • Ontario
    • Ottawa, Ontario, Canada, K1H7W9
    • Toronto, Ontario, Canada, M4S 1Y2
  • Quebec
    • Mirabel, Quebec, Canada, J7J 1L2
    • Montreal, Quebec, Canada, H2X 1N8
    • Montreal, Quebec, Canada, H1T 1P6
    • Pointe-Claire, Quebec, Canada, H9R 4S3
    • Shawinigan, Quebec, Canada, G9N 2H6
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4S 0A2
• Mexico
  • Mexico Df, Mexico, 11000
  • México
    • Mexico, México, Mexico, 16720
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
  • California
    • Beverly Hills, California, United States, 90211
    • Carmichael, California, United States, 95608
    • San Diego, California, United States, 92103
    • San Diego, California, United States, 92108
    • Santa Monica, California, United States, 90403
    • Torrance, California, United States, 90509
  • Colorado
    • Littleton, Colorado, United States, 80122
  • Florida
    • Boynton Beach, Florida, United States, 33437
    • Jacksonville, Florida, United States, 32216
    • West Palm Beach, Florida, United States, 33409
  • Idaho
    • Boise, Idaho, United States, 83702
  • Illinois
    • Chicago, Illinois, United States, 60612
  • Indiana
    • Newburgh, Indiana, United States, 47630
    • South Bend, Indiana, United States, 46601
  • Louisiana
    • Amite, Louisiana, United States, 70422
    • Marrero, Louisiana, United States, 70072
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
  • Michigan
    • Saginaw, Michigan, United States, 48602
  • Missouri
    • Chesterfield, Missouri, United States, 63017
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
  • Nevada
    • Las Vegas, Nevada, United States
    • LasVegas, Nevada, United States, 89106
  • New Jersey
    • Moorestown, New Jersey, United States, 08057
    • New Brunswick, New Jersey, United States, 08901
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
  • Oregon
    • Medford, Oregon, United States, 97504
    • Portland, Oregon, United States, 97239
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
    • Pittsburgh, Pennsylvania, United States, 15206
  • South Carolina
    • Columbia, South Carolina, United States, 29201
  • Tennessee
    • Clarksville, Tennessee, United States, 37043
  • Texas
    • Houston, Texas, United States
    • Houston, Texas, United States, 77030
  • Vermont
    • Burlington, Vermont, United States, 05401
  • Virginia
    • Norfolk, Virginia, United States, 23507
  • Washington
    • Seattle, Washington, United States, 98105

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women who have >/= 80 mL blood loss during their menstrual cycles and desire contraception

Exclusion Criteria:

• Post menopausal menstrual cycle < 21 days or > 35 days
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levonorgestrel Intrauterine System (LNG IUS) 20µg per 24 hours; Initial release rate of 20µg Levonorgestrel IUS (Mirena, BAY86-5028) per day for 6 cycles.	Drug: Levonorgestrel IUS (Mirena, BAY86-5028); Initial release rate of 20µg Levonorgestrel IUS (Mirena, BAY86-5028) per day for 6 cycles.
Active Comparator: Medroxyprogesterone acetate (MPA); Medroxyprogesterone acetate (MPA, Provera), oral, 10mg per tablet on 10 consecutive days of each cycle for 6 cycles.	Drug: Medroxyprogesterone acetate; Medroxyprogesterone acetate (MPA, Provera), oral, 10mg per tablet on 10 consecutive days of each cycle for 6 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Change in Absolute Value From Baseline Menstrual Blood Loss (MBL) to the End-of-study MBL (Cycle 6)	The MBL for each cycle included intermenstrual bleeding in addition to withdrawal bleeding. Baseline MBL was the composite MBL measured during each of the cycles during the Screening Phase. End-of-study MBL was measured during Cycle 6 of the Treatment Phase.	Baseline and up to 6 months
Percentage of Patients With Successful Treatment	End-of-study MBL < 80 mL and a decrease to a value no greater than 50% of the Baseline MBL was considered to be treatment success.	At 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline MBL to End of Study MBL (Cycle 6)	The percent change = {(End of Study MBL - Baseline MBL)/Baseline MBL} x 100.	Baseline and up to 6 months
Absolute Change From Baseline MBL to Mid-study MBL (Cycle 3)	The MBL for each cycle included intermenstrual bleeding in addition to withdrawal bleeding. Mid-study MBL was measured during Cycle 3 of the Treatment Phase.	Baseline and up to 3 months
Percent Change From Baseline MBL to Mid-study MBL (Cycle 3)	The percent change = {(Mid-study MBL - Baseline MBL)/Baseline MBL} x 100.	Baseline and up to 3 months
Percentage of Subjects Who Completed the Study in Levonorgestrel Intrauterine System (LNG IUS) Group		Baseline and up to 6 months
Total Number of Bleeding Days	In the LNG IUS group, each cycle has 30 days. In the MPA group, each menstrual cycle starts on the 1st bleeding day (withdrawal bleeding) and lasts until the last non-bleeding day before next withdrawal bleeding starts.	Baseline and up to 6 months
Total Number of Spotting and Bleeding Days	In the LNG IUS group, each cycle has 30 days. In the MPA group, each menstrual cycle starts on the 1st bleeding day (withdrawal bleeding) and lasts until the last non-bleeding day before next withdrawal bleeding starts.	Baseline and up to 6 months
Total Number of Spotting Days	In the LNG IUS group, each cycle has 30 days. In the MPA group, each menstrual cycle starts on the 1st bleeding day (withdrawal bleeding) and lasts until the last non-bleeding day before next withdrawal bleeding starts.	Baseline and up to 6 months
Total Number of Bleeding Episodes	A bleeding episode is defined as a light, normal or heavy bleeding, during a minimum of one day. In the LNG IUS group, each cycle has 30 days. In the MPA group, each menstrual cycle starts on the 1st bleeding day (withdrawal bleeding) and lasts until the last non-bleeding day before next withdrawal bleeding starts.	Baseline and up to 6 months
Percent Change in Hemoglobin		Baseline and up to 6 months
Percent Change in Hematocrit		Baseline and up to 6 months
Percent Change in Serum Ferritin		Baseline and up to 6 months
Percentage of Patients With Improvement in the Investigator Global Assessment Scale	"Improved" is classified as 'very much improved', 'much improved', or 'improved' and "not improved" is classified as 'no change', 'worse', 'much worse', or 'very much worse'	Up to 6 months
Percentage of Patients With Improvement in the Patients Overall Assessment Scale	"Improved" is classified as 'very much improved', 'much improved', or 'improved' and "not improved" is classified as 'no change', 'worse', 'much worse', or 'very much worse'.	Up to 6 months

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Endrikat J, Vilos G, Muysers C, Fortier M, Solomayer E, Lukkari-Lax E. The levonorgestrel-releasing intrauterine system provides a reliable, long-term treatment option for women with idiopathic menorrhagia. Arch Gynecol Obstet. 2012 Jan;285(1):117-21. doi: 10.1007/s00404-011-1902-1. Epub 2011 Apr 8.
• Kaunitz AM, Bissonnette F, Monteiro I, Lukkari-Lax E, DeSanctis Y, Jensen J. Levonorgestrel-releasing intrauterine system for heavy menstrual bleeding improves hemoglobin and ferritin levels. Contraception. 2012 Nov;86(5):452-7. doi: 10.1016/j.contraception.2012.07.018. Epub 2012 Sep 7.
• Kaunitz AM, Bissonnette F, Monteiro I, Lukkari-Lax E, Muysers C, Jensen JT. Levonorgestrel-releasing intrauterine system or medroxyprogesterone for heavy menstrual bleeding: a randomized controlled trial. Obstet Gynecol. 2010 Sep;116(3):625-632. doi: 10.1097/AOG.0b013e3181ec622b. Erratum In: Obstet Gynecol. 2010 Oct;116(4):999.

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: August 2, 2006
• First Submitted That Met QC Criteria: August 2, 2006
• First Posted (Estimate): August 4, 2006

Study Record Updates

• Last Update Posted (Estimate): December 9, 2013
• Last Update Submitted That Met QC Criteria: November 14, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Idiopathic Menorrhagia
• Additional Relevant MeSH Terms: Pathologic Processes; Uterine Diseases; Hemorrhage; Menstruation Disturbances; Uterine Hemorrhage; Menorrhagia; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Contraceptive Agents, Male; Levonorgestrel; Medroxyprogesterone Acetate; Medroxyprogesterone
• Other Study ID Numbers: 91518; 309849 (Other Identifier: Bayer)