Management of Initial Bleeding/Spotting Associated With the Levonorgestrel-releasing Intrauterine System (MIRENA)

Study Overview
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Brief Summary
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The purpose of the study is to investigate if the study drugs (tranexamic acid or mefenamic acid) can control irregular bleeding during the first 3 months of using Mirena. The study drugs tested are tested against placebo (dummy medication not containing any active drug). Treatment period is followed by a one-month period when study drugs are not taken but Mirena use is continued.

Official Title
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International, Prospective, Double-blind, 3-arm Comparative, Randomized, Placebo-controlled Phase IV Study on the Effect of Counseling and Either Tranexamic Acid or Mefenamic Acid or Placebo, on the Management of Bleeding/Spotting in Women Using the Levonorgestrel-releasing Intrauterine System (MIRENA) for Contraception.

Conditions
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Uterine Hemorrhage

Intervention / Treatment
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* Drug: Tranexamic acid
* Drug: Mefenamic acid
* Drug: Placebo
* Drug: Mirena (Levonorgestrel IUS, BAY86-5028)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent Healthy female subjects requesting contraception Age: 18 - 45 years inclusive Successful interval insertion of MIRENA History of regular cyclic menstrual periods Normal or clinically insignificant cervical smear not requiring further follow up Exclusion Criteria: Pregnancy or lactation Climacteric symptoms prior to the screening visit Known or suspected clinically significant ovarian cysts, endometrial polyps, fibroids, or other genital organ pathology, that, in the opinion of the investigator, may interfere with the assessment of the bleeding profile during the study Undiagnosed abnormal genital bleeding Current or history of thrombembolic disease, or established risk factors for venous thromboembolism Current migraine, focal migraine with asymmetrical visual loss or other symptoms indicating transient cerebral ischemia, or exceptionally severe headaches Hypersensitivity to any ingredient of the investigational medicinal products or the non-investigational medicinal product Daily or frequent use of a nonsteroidal anti-inflammatory drug (NSAIDs) for any condition Not willing to use nonsteroidal anti-inflammatory drug (NSAIDs) medication as pain medication during the double blind treatment period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tranexamic acid + Mirena (Levonorgestrel IUS, BAY86-5028)<br>Subjects with successful MIRENA insertion will receive treatments with tranexamic acid | Drug: Tranexamic acid<br>* 500 mg 3 times daily per oral during bleeding/spotting episodes<br>Drug: Mirena (Levonorgestrel IUS, BAY86-5028)<br>* In vitro release rate 20 microgram/24 hours. Intrauterine system<br>|
| Experimental: mefenamic acid + Mirena (Levonorgestrel IUS, BAY86-5028)<br>Subjects with successful MIRENA insertion will receive treatments with mefenamic acid | Drug: Mefenamic acid<br>* 500 mg 3 times daily per oral during bleeding/spotting episodes<br>Drug: Mirena (Levonorgestrel IUS, BAY86-5028)<br>* In vitro release rate 20 microgram/24 hours. Intrauterine system<br>|
| Placebo Comparator: placebo + Mirena (Levonorgestrel IUS, BAY86-5028)<br>Subjects with successful MIRENA insertion will receive placebo | Drug: Placebo<br>* 3 times daily per oral during bleeding/spotting episodes<br>Drug: Mirena (Levonorgestrel IUS, BAY86-5028)<br>* In vitro release rate 20 microgram/24 hours. Intrauterine system<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary efficacy variable will be the cumulative number of bleeding / spotting days |  | During 90 day double-blind treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To describe and compare the bleeding patterns observed in women during treatment period |  | 90 day treatment period | 
| To describe and compare the bleeding patterns observed in women during follow-up period |  | During the 30 day follow-up period | 
| Satisfaction with oral blinded study drug treatment for bleeding / spotting |  | 90 day treatment period | 
| Occurrence of dysmenorrhea |  | During 120 day study period | 
| Continuation rate with study drug |  | During the 90 day treatment period | 
| Continuation rate with Mirena |  | During 120 day study period | 
| Adverse Events Collection |  | Until day 120 | 
| Number of spotting-only days |  | During the 90-day treatment period | 
| Number of bleeding / spotting episodes |  | During the 90-day treatment period | 
| Length of bleeding / spotting episodes |  | During the 90-day treatment period | 
| Number of bleeding days with heavy intensity |  | During the 90-day treatment period | 
| Change in the number of B/S days between Day 60 and Day 90 of MIRENA use and the 30-day follow-up period |  | Up to day 120 | 
| Satisfaction with levonorgestrel-releasing intrauterine system |  | Up to day 120 | 
| Number of days of pain medication for dysmenorrhea during the 90 day treatment period |  | During the 90-day treatment period | 
| Number of bleeding-only days |  | During the 90-day treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uterine Hemorrhage, Contraception, Contraceptive Methods, Intrauterine devices, Mirena