Levonorgestrel Contraceptive Intrauterine Systems (LCS) Pearl Index Study

Study Overview
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Brief Summary
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This is a study on a new low dose levonorgestrel contraceptive intrauterine systems (LCS). The purpose of the study is to investigate which of the 2 administered doses is the lowest effective intrauterine dose of Levonorgestrel (LNG) administered via the LCS for contraception during 3 years. The study was amended: the LCS16 arm will be extended up to 5 years

Detailed Description
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Drop out-rate will be covered in Participant flow section.

Official Title
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Multi-Center, Open-Label, Randomized Study to Assess the Safety and Contraceptive Efficacy of Two Doses ( in vitro12 µg/24h and 16 µg/24h) of the Ultra Low Dose Levonorgestrel Contraceptive Intrauterine Systems (LCS) for a Maximum of 3 Years in Women 18 to 35 Years of Age and an Extension Phase of the 16µg/24h Dose Group (LCS16 Arm) up to 5 Years

Conditions
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Contraception

Intervention / Treatment
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* Drug: LCS12
* Drug: LCS16


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 35 years (inclusive), in good general health and requesting contraception. Has regular menstrual cycles (length of cycle 21-35 days) (i.e., endogenous cyclicity without hormonal contraceptive use). Exclusion Criteria: Known or suspected pregnancy or is lactating. History of ectopic pregnancies. Any genital infection (until successfully treated). Abnormal uterine bleeding of unknown origin.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LCS12<br>Intrauterine levonorgestrel contraceptive system (LCS), releasing levonorgestrel (LNG) 12 microg/24 h in vitro | Drug: LCS12<br>* Intrauterine system (IUS) with Levonorgestrel, in vitro releasing rate 12 microg/24 h<br>|
| Experimental: LCS16<br>Intrauterine levonorgestrel contraceptive system (LCS), releasing levonorgestrel (LNG) 16 microg/24 h in vitro | Drug: LCS16<br>* Intrauterine system (IUS) with Levonorgestrel, in vitro releasing rate 16 microg/24 h<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pearl Index up to 3 Years | The unadjusted 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 at risk of getting pregnant. | Up to 3 years | 
| Pearl Index for LCS16 up to 5 Years | The unadjusted Pearl Index (PI) is defined as the number of pregnancies per 100 woman years. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 1 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. | Day 1 to Day 90 | 
| Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 2 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. | Day 91 to Day 180 | 
| Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 3 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. | Day 181 to Day 270 | 
| Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 4 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. | Day 271 to Day 360 | 
| Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 12 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. | Day 991 to Day 1080 | 
| Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 1 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. | Day 1 to Day 30 | 
| Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 2 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. | Day 31 to Day 60 | 
| Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 3 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. | Day 61 to Day 90 | 
| Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 4 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. | Day 91 to Day 120 | 
| Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 12 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. | Day 331 to Day 360 | 
| Number of Participants With/Without Ovulation - Year 1 | Serum concentrations of progesterone were analyzed. All subjects with progesterone values equal to or greater than 2.5 ng/ml were assessed as having an ovulation. | For six weeks in the second half of Year 1 | 
| Number of Participants With/Without Ovulation - Year 2 | Serum concentrations of progesterone were analyzed. All subjects with progesterone values equal to or greater than 2.5 ng/ml were assessed as having an ovulation. | For six weeks in the second half of Year 2 | 
| Number of Participants With/Without Ovulation - Year 3 | Serum concentrations of progesterone were analyzed. All subjects with progesterone values equal to or greater than 2.5 ng/ml were assessed as having an ovulation. | For six weeks in the second half of Year 3 | 
| Average Total Cervical Score - Year 1 | Cervical mucus samples were analyzed to determine any effects of progesterone on the cervical mucus. Range of score: 0 (high contraceptive efficacy) to 12 (low contraceptive efficacy) | For six weeks in the second half of Year 1 | 
| Average Total Cervical Score - Year 2 | Cervical mucus samples were analyzed to determine any effects of progesterone on the cervical mucus. Range of score: 0 (high contraceptive efficacy) to 12 (low contraceptive efficacy) | For six weeks in the second half of Year 2 | 
| Average Total Cervical Score - Year 3 | Cervical mucus samples were analyzed to determine any effects of progesterone on the cervical mucus. Range of score: 0 (high contraceptive efficacy) to 12 (low contraceptive efficacy) | For six weeks in the second half of Year 3 | 
| Classification of Endometrium - Year 1 | The histological evaluation of the endometrium examined the effects of progesterone on the endometrium | At Year 1 | 
| Classification of Endometrium - Year 2 | The histological evaluation of the endometrium examined the effects of progesterone on the endometrium | At Year 2 | 
| Classification of Endometrium - Year 3 / End of Study | The histological evaluation of the endometrium examined the effects of progesterone on the endometrium | At Year 3 / End of study | 
| Degree of User Overall Satisfaction With Study Treatment | Overall user satisfaction was assessed by a questionnaire given to participants at the end of the study. The questionnaire was only given to participants whose end-of-study visit occurred after implementation of Protocol Amendment 3. | At the end of study/Year 3 | 
| Number of Participants With Partial or Total Expulsion | If LCS was displaced, but still in the cervical canal, it was assessed as being partially displaced. If LCS was expelled from the uterus, it was assessed as a total expulsion. | Up to 3 years | 
| Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 13 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. | Day 1081 to Day 1170 | 
| Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 20 | The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience. | Day 1711 to Day 1800 | 
| Degree of User Overall Satisfaction With Study Treatment up to 5 Years | Overall user satisfaction was assessed by a questionnaire given to participants at the end of the study. The questionnaire was only given to participants whose end-of-study visit occurred after implementation of Protocol Amendment 3. | At the end of study/Year 5 | 
| Number of Participants With Partial or Total Expulsion up to 5 Years | If LCS was displaced, but still in the cervical canal, it was assessed as being partially displaced. If LCS was expelled from the uterus, it was assessed as a total expulsion. | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Contraception, Intrauterine, IUD, IUS