Dose-finding Study for the Ultralow-dose Levonorgestrel Intrauterine Contraceptive System (LCS)

Study Overview
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Brief Summary
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The purpose of this study is to investigate if drug doses lower than the one released from Mirena® would be as effective for contraception as Mirena®. Subjects participating in the study will be randomly assigned to be inserted with any of the three different intrauterine systems (IUSs). The IUSs are nearly alike except that the amount of hormone released from them is different.

Detailed Description
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The study has previously been posted by Schering AG, Germany. Schering AG, Germany has been renamed to Bayer Schering Pharma AG, Germany. Bayer Schering Pharma AG, Germany is the sponsor of the trial. Although the title of the study describes open, it was in fact single-blinded. Issues on side effects are addressed in the Adverse Event section.

Official Title
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Multi-center, Open, Randomized, Dose Finding Phase II Study to Investigate Ultra Low Dose Levonorgestrel Contraceptive Intrauterine Systems (LCS) Releasing Different Amounts of Levonorgestrel Compared to MIRENA in Nulliparous and Parous Women in Need of Contraception.

Conditions
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Contraception

Intervention / Treatment
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* Drug: Levonorgestrel IUS (BAY86-5028, G04209B)
* Drug: Levonorgestrel IUS (BAY86-5028, G04209C)
* Drug: Levonorgestrel IUS (Mirena, BAY86-5028)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with or without children and good general health and in need of contraception. Regular menstrual cycle without hormonal contraceptives. Exclusion Criteria: Pregnant or lactating. Last delivery or abortion less than 12 weeks ago. Previous pregnancies outside the womb. Previous pelvic infections. Abnormal bleeding. Abnormal uterine cavity. Climacteric signs. Genital cancer. Liver diseases. Alcoholism or drug abuse.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LCS12<br>Levonorgestrel intrauterine contraceptive system (LCS) releasing 12 microg/24h in vitro | Drug: Levonorgestrel IUS (BAY86-5028, G04209B)<br>* Levonorgestrel intrauterine contraception system (IUS) releasing 12 microg/24 h in vitro, to be used for three years<br>|
| Experimental: LCS16<br>Levonorgestrel intrauterine contraceptive system (LCS) releasing 16 microg/24h in vitro | Drug: Levonorgestrel IUS (BAY86-5028, G04209C)<br>* Levonorgestrel intrauterine contraception system (IUS) releasing 16 microg/24 h in vitro, to be used for three years<br>|
| Active Comparator: IUS20 (Mirena)<br>Levonorgestrel intrauterine system (IUS) releasing 20 microg/24h in vitro | Drug: Levonorgestrel IUS (Mirena, BAY86-5028)<br>* Levonorgestrel Intrauterine contraception system (IUS) releasing 20 microg/24 h to be used for three years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pearl Index | The Pearl Index (PI) is defined as the number of pregnancies per 100 woman years. The 3-year PI was obtained by dividing the number of pregnancies that occurred during the first three years of treatment by the time (in 100 women years) that the women were under risk of getting pregnant. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Total or Partial Expulsions | The numbers of subjects with partial or total IUS expulsions (device displaced from its correct position within the uterus) were to be given by treatment. | Up to 3 years | 
| Bleeding Pattern by 90-day Reference Periods - Reference Period 1 | Subjects kept a bleeding diary and recorded any bleeding every day by category: none, spotting, light, normal or heavy. Any missing data were obtained by direct questioning. | day 1 to day 90 | 
| Bleeding Pattern by 90-day Reference Periods - Reference Period 2 | Subjects kept a bleeding diary and recorded any bleeding every day by category: none, spotting, light, normal or heavy. Any missing data were obtained by direct questioning. | day 91 to day 180 | 
| Bleeding Pattern by 90-day Reference Periods - Reference Period 3 | Subjects kept a bleeding diary and recorded any bleeding every day by category: none, spotting, light, normal or heavy. Any missing data were obtained by direct questioning. | day 181 to day 270 | 
| Bleeding Pattern by 90-day Reference Periods - Reference Period 4 | Subjects kept a bleeding diary and recorded any bleeding every day by category: none, spotting, light, normal or heavy. Any missing data were obtained by direct questioning. | day 271 to day 360 | 
| Bleeding Pattern by 90-day Reference Periods - Reference Period 12 | Subjects kept a bleeding diary and recorded any bleeding every day by category: none, spotting, light, normal or heavy. Any missing data were obtained by direct questioning. | day 991 to day 1080 |