LCS12 vs. ENG Subdermal Implant (Nexplanon) Discontinuation Rate Study

Study Overview
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Brief Summary
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The primary objective is to demonstrate that discontinuation rates in women (ages 18-35 years inclusive) using LCS12 are not higher than those seen in women using ENG subdermal implant over a period of 12 months. Secondary objectives are to observe the bleeding patterns, adverse event profiles and the occurrence of unintended pregnancies. Additionally, data on user satisfaction, IUS expulsions and implant site complications will be collected.

Official Title
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Multicenter, Open-label, Randomized, Controlled Parallel-group Study to Assess Discontinuation Rates, Bleeding Patterns, User Satisfaction and Adverse Event Profile of LCS12 in Comparison to Etonorgestrel Subdermal Implant Over 12 Months of Use in Women 18 to 35 Years of Age

Conditions
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Contraception

Intervention / Treatment
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* Drug: LNG-IUS (BAY 86-5028)
* Drug: 68 mg etonorgestrel implant for subdermal use (Nexplanon)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated the informed consent Healthy female subjects in need of contraception Age: between 18 and 35 years (inclusive) at Screening visit Normal or clinically insignificant cervical smear not requiring further follow up (a cervical smear has to be taken at screening visit or a normal result has to be documented within the previous six months). HPV testing in subjects with ASCUS can be used as an adjunctive test. Subjects with ASCUS can be included if they are negative for high-risk HPV strains. History of regular cyclic menstrual periods as determined by subject's history, subject has regular menstrual cycles (length of cycle 21 - 35 days). (Subject's history while not using hormonal contraceptives is sufficient, no washout period is required). Subject is willing and able to attend the scheduled study visits and to comply with the study procedures. Exclusion Criteria: Pregnancy or currently lactating Vaginal delivery, cesarean delivery or abortion within 6 weeks prior to Screening visit. Note: Postpartum LCS12 insertions should be postponed until uterus is fully involuted, however not earlier than 6 weeks after delivery. If involution is substantially delayed, consider waiting until 12 weeks postpartum. Infected abortion or postpartum endometritis within 3 months prior to the Screening visit. Undiagnosed abnormal genital bleeding. Acute lower genital tract infection (until successfully treated) Acute or history of recurrent, pelvic inflammatory disease. Congenital or acquired uterine anomaly or any distortion of the uterine cavity (e.g. by fibroids) that, in the opinion of the investigator or designee, would cause problems during insertion, retention, or removal of LCS12. (Note: a pre-insertion ultrasound is not necessary. However, if based on subject history or physical exam findings, there is a suspicion of uterine anomaly or any distortion of the uterine cavity, appropriate diagnostic measures should be taken prior to randomization) History of, diagnosed or suspected genital malignancy, and untreated cervical dysplasia. Clinically significant endometrial polyp(s) that, in the opinion of the investigator or designee, may interfere with the assessment of the bleeding profile during the study. (Note: a pre-insertion ultrasound is not necessary. However, if based on subject history or physical exam findings, there is a suspicion of polyps, appropriate diagnostic measures should be taken prior to randomization.) Has previously failed screening for this study Any disease or condition that may worsen under hormonal treatment according to the assessment and opinion of the investigator. The following are examples of such conditions or diseases: Cardiovascular Presence or a history of venous or arterial thrombotic/thromboembolic events (e.g., deep venous thrombosis, pulmonary embolism, myocardial infarction) or of a cerebrovascular accident, including prodromi (e.g. transient ischemic attack, angina pectoris) Repeated measurements of systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg. Liver Presence or history of liver tumors (benign or malignant) Presence or history of severe hepatic disease as long as liver function values have not returned to normal Jaundice and/or pruritus related to cholestasis (Gilbert's syndrome excepted) History of cholestatic jaundice associated with pregnancy or previous COC use - Other diseases: Malignant or premalignant disease (excluding melanoma) History of migraine with focal neurologic symptoms Any diseases or conditions that might interfere with the conduct of the study or the interpretation of the results Clinically significant ovarian cyst (defined as abnormal non-functional cysts) (Note: a pre-insertion ultrasound is not necessary. However, if based on subject history or physical exam findings, there is a suspicion of a clinically significant cyst, appropriate diagnostic measures should be taken prior to randomization.) Any diseases or conditions that can compromise the function of the body systems and could result in altered absorption, excessive accumulation, impaired metabolism or altered excretion of the study medication Other contraceptive methods: Sterilization Use of any long-acting injectable sex-hormone preparations within 10 months prior to the Randomization visit. The use of non study oral, vaginal, or transdermal hormonal contraception, intrauterine devices (IUDs) with or without hormonal release, and implants is prohibited during treatment.

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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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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: LNG-IUS (BAY 86-5028)<br>* LCS12 insertion will occur at randomization visit (Visit 2). Duration of study treatment is 12 months with an follow-up extension for up to 3 years<br>|
| Active Comparator: Arm 2<br> | Drug: 68 mg etonorgestrel implant for subdermal use (Nexplanon)<br>* Implant insertion will occur at randomization visit (Visit 2). Duration of study treatment is 12 months, may be continued up to 3 years under standard care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Discontinuation rate by treatment group |  | at 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Discontinuation rates by treatment group |  | at 6 months and by reason at 6 and 12 months | 
| Overall satisfaction rating and questionnaires on User satisfaction and bleeding and Contraceptive tolerability |  | at 6 and 12 months | 
| Pregnancy rate, as determined by Pearl index |  | at 12 months |