A pivotal, multicentre, randomised, open-label, parallel-group trial on contraceptive efficacy, safety and tolerability of LVDS (Levonorgestrel Vaginal Delivery System) during 9 cycles in comparison with Desogestrel tablets 0.075 mg.

The primary objective of this pivotal, multicentre, randomised, open-label, parallel-group trial is to demonstrate the **contraceptive efficacy** of the Levonorgestrel Vaginal Delivery System (LVDS) over nine cycles, in comparison with Desogestrel tablets 0.075 mg. This objective is clinically relevant as it addresses the prevention of pregnancy, providing an alternative contraceptive method that may offer different benefits in terms of administration and patient compliance.

Secondary objectives include:

• To demonstrate the contraceptive efficacy of LVDS, further supporting its primary objective.
• To assess the safety and tolerability of LVDS, ensuring that the system is not only effective but also safe and well-tolerated by users.

The clinical trial focuses on the **prevention of pregnancy** and involves a study population consisting exclusively of sexually active, postmenarcheal, and premenopausal female subjects aged 18 years and older. The trial does not include male participants. The participants are at risk of pregnancy, including breastfeeding women, and are required to have a systolic blood pressure of ≤ 140 mm Hg and diastolic blood pressure of ≤ 90 mm Hg, with controlled hypertension being permissible. The trial population was selected based on specific criteria, including women who have never used hormonal contraceptives, those who have had a hormonal contraceptive-free period, or those who directly switch from another hormonal contraceptive. Participants must be willing to use the trial contraception method they are randomized to, either a vaginal ring or oral tablet, for nine 28-day cycles. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is a pivotal, multicentre, **randomised**, open-label, parallel-group study designed to evaluate the contraceptive efficacy, safety, and tolerability of the **Levonorgestrel Vaginal Delivery System** (LVDS) compared to **Desogestrel** tablets. The trial will span nine cycles, with an estimated completion date of March 30, 2025. Participants will be randomly assigned to either the LVDS or Desogestrel group, with the primary objective being to demonstrate the contraceptive efficacy of LVDS. The primary endpoint is the overall Pearl Index in non-breastfeeding women aged 35 years or younger at the time of trial enrolment. Secondary endpoints include various efficacy and safety measures, such as the Pearl Index in different age groups, method failure rates, and adverse events.

Study visits are structured to ensure comprehensive data collection and participant safety. The inclusion visit, or screening visit, will confirm eligibility based on criteria such as age, sexual activity, and health status. Participants must be sexually active, postmenarcheal, and premenopausal females aged 18 years or older, at risk of pregnancy, and willing to use the assigned trial contraception for nine 28-day cycles. Follow-up visits will occur throughout the trial to monitor efficacy and safety, including assessments of vital signs, physical and gynecological examinations, and laboratory tests. The end-of-study visit will conclude the trial, with final evaluations and data collection.

The expected duration of participant involvement is approximately 252 days, corresponding to the nine-cycle treatment period. Conditions that may lead to early termination from the study include non-compliance with the trial protocol, adverse events, or withdrawal of consent. Participants are required to agree not to participate in other clinical trials during the study, although participation in non-interventional studies is permitted. The trial is not classified as a low-intervention study and falls under category 2, indicating a phase III trial to demonstrate the efficacy, safety, and tolerability of the test product in the target population.

The clinical trial involves the administration of two experimental medications to evaluate their contraceptive efficacy, safety, and tolerability. The first medication is **Desogestrel**, marketed under the name "Desirett 75 Mikrogramm Filmtabletten." This medication is presented in the form of film-coated tablets, with each tablet containing 75 micrograms of the active substance desogestrel. The route of administration is oral, and the dosage regimen involves a daily intake of one tablet. The maximum treatment period for this medication is 252 days, corresponding to nine menstrual cycles. The product is manufactured by Exeltis Germany GmbH and is classified under the ATC code G03AC09. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence.

The second experimental medication is the **Levonorgestrel Vaginal Delivery System 75**, identified by the sponsor product code CH211-75. This product is a vaginal delivery system containing 75 micrograms of the active substance levonorgestrel. The administration route is vaginal, and the system is designed to release the active substance consistently over the treatment period. Similar to the desogestrel tablets, the maximum treatment duration is 252 days, covering nine menstrual cycles. This product is manufactured by Exeltis France. Participant compliance with the use of the vaginal delivery system is closely monitored to ensure proper usage and effectiveness.

Both medications are chemically derived and are not classified as orphan drugs. The trial is structured as a pivotal, multicentre, randomised, open-label, parallel-group study. The primary objective is to demonstrate the contraceptive efficacy of the Levonorgestrel Vaginal Delivery System in comparison to the Desogestrel tablets. No non-experimental treatments, such as standard-of-care therapy or placebo, are utilized in this study. The trial does not involve any paediatric formulations, and the products are not intended for paediatric use.

The clinical trial aims to assess the contraceptive efficacy of the Levonorgestrel Vaginal Delivery System (LVDS) compared to Desogestrel tablets. The primary efficacy endpoint is the Overall **Pearl Index** (PI) in non-breastfeeding women aged ≤ 35 years at the time of trial enrollment. Secondary efficacy endpoints include the overall PI in women aged ≤ 35 years and those > 35 years, PI after correction for back-up contraception and sexual activity, PI for method failure, and pregnancy ratio by life table analysis. These endpoints will be evaluated in both age groups.

Secondary safety and tolerability endpoints include adverse events, vital signs, physical and gynecological examinations, mastodynia/mastalgia/dysmenorrhea, and various bleeding parameters such as the proportion of subjects with bleeding during Cycles 2-9, bleeding/spotting in each cycle, absence of bleeding, and prolonged bleeding. Additional assessments include the number of days per cycle with bleeding/spotting, number of bleeding/spotting episodes, and duration of these episodes. Clinical laboratory parameters, including haematology, biochemistry, and specific biomarkers, will also be evaluated. The trial will utilize the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) to assess the acceptability of the investigational product.