anticonceptie birthcontrol contraception
Conditions
Interventions
Each treatment cycle will be approximately 28-days.
* ENG-E2 vaginal ring group: 21 days with the ENG-E2 vaginal ring inserted,
followed by seven (7) days ring-free.
* LNG-EE tablet group: 21 days o
Sponsors
Merck Sharp & Dohme (MSD)
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: VISIT 1:;- Provide written informed consent for the trial. ;- Be a premenopausal female, aged * 18 to *50 years at the time of enrollment.;- If heterosexually active, agrees to have male partner use a condom during the trial period as applicable, unless the subject or her partner is surgically sterilized;- Have a body mass index (BMI) *18 and *35 kg/m2.;- Be in good physical and mental health.;- Be able and willing (in the opinion of the investigator) to adhere to study treatments and to all required study procedures, including study visits.;VISIT 2:;- Have had at least 1 menstruation since Visit 1. ;VISIT 3:;- Have a negative urine pregnancy test at Visit 3.;- Continue to meet all inclusion criteria.
Exclusion criteria
Exclusion criteria: - Is currently smoking or uses tobacco/nicotine containing products and is * 35 years of age.;- Has a history of venous thromboembolic (VTE) events (deep vein thrombosis, pulmonary embolism) or a history of arterial thrombotic or thromboembolic (ATE) events (myocardial infarction, stroke, or peripheral arterial events), or a history of transient ischemic attack, angina pectoris, claudication, or pulmonary hypertension.;- Is at higher risk of VTE events due to recent prolonged immobilization within 2 weeks prior to screening or has a hereditary or acquired predisposition or elevated risk for venous or arterial thrombosis;- Is <35 years of age and has a history of migraine with aura or focal neurological symptoms; or is *35 years of age and has a history of migraines (with or without aura or focal neurologic symptoms);- Has a history of severe dyslipoproteinemia;- Has diabetes mellitus or known insulin insensitivity;- Has clinically significant liver disease;- Has thyroid, adrenal or androgenic disorder (e.g., polycystic ovary syndrome, congenital adrenal hyperplasia, Cushing*s disease or syndrome, etc).;- Has received any treatment listed in protocol Table 1 more recently than the washout period indicated in Table 1 and/or needs to continue to receive any treatment listed in during the current trial.;NOTE: Refer to protocol for complete list
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The EMA requires that all new combined hormonal contraception (CHC) products assess the impact of treatment on hemostatic parameters by providing comparative pharmacodynamic data of the new CHC to a marketed EE-and levonorgestrel- or desogestrel-containing COC, with an established risk profile [3]. The EMA acknowledges that there are no generally accepted surrogate endpoints for rare risks associated with CHCs, such as cardiovascular events or VTE. The Guideline on Clinical Investigation of Steroid Contraceptives in Women (July 2005) [3], suggests that the biologic variables that may reflect pharmacodynamic alterations, possibly related to VTE risk, may include, prothrombin fragment 1+2, APC resistance (ETP-based and APTT-based), d-dimer, factor VII, factor VIII, factor II, antithrombin, protein S, protein C, and SHBG. For the current study, a subset of hemostatic parameters, those previously shown to be differentially altered by COCs containing EE or E2 based on published reports [1, 2, 11], were selected as the primary study endpoint. The hemostatic parameters selected to support the primary study objective include Tissue Factor Pathway Inhibitor antigen (TFPI), protein S antigen (total), antithrombin activity, d-dimer, and normalized Activated Protein C resistance ratio (nAPCrr). A combination of hemostatic parameters was selected considering that no individual hemostatic parameter has been established as the single-most predictor of VTE risk. The proposed duration for assessment of hemostatic parameters is after three cycles of treatment with the ENG-E2 vaginal ring. The change from baseline to end of Cycle 3 for each parameter will be determined and an estimate of the treatment differences provided, along with the 95% confidence interval (CI). Three months is considered to be a sufficient duration of time to detect hormonal effects on the specified hemostatic parameters. In the study by Agren et al., hemostatic parameters measured afte | — |
Secondary
| Measure | Time frame |
|---|---|
| A secondary objective of this study is to assess the effects of the ENG-E2 vaginal ring on additional hemostatic parameters, to ensure that a comprehensive characterization with respect to coagulation is provided, including those cited by the EMA for consideration in the evaluation of new CHCs. The additional hemostatic parameters include: prothrombin fragment 1+2, Protein S (free), APTT-based APCrr, Factor VII, Factor VIII, Factor II, and protein C. Similar to the primary objective, the change from baseline for each parameter after 3 months of treatment with the ENG-E2 vaginal ring will be compared with LNG-EE oral tablets. An additional secondary endpoint will include CRP and SHBG. C-reactive protein (CRP), a biomarker of inflammation and is considered to be an independent cardiovascular risk marker. CRP has been shown to become elevated after treatment with CHCs [1, 4]. Sex hormone binding globulin (SHBG) has been characterized as a *biomarker* of estrogen-related induction of hepatic protein synthesis, which includes procoagulant hemostatic parameters. In fact, the net SHBG change associated with a CHC depends on the estrogenic-androgenic balance, i.e., the extent to which the estrogen-induced increase is counteracted by the androgenic properties of the progestagen. The change from baseline for each parameter after 3 months of treatment with the ENG-E2 vaginal ring will be compared with the LNG-EE COC. In addition to assessing impact on hemostatic parameters relative to a CHC (LNG-EE), this study will evaluate whether there is any detectable alteration in hemostatic parameters relative to a non-treated control group. To accomplish this, the change from baseline during ENG-E2 treatment on all of the hemostatic parameters included as the primary or secondary objective will be compared with changes from baseline in these hemostatic factors in untreated women. Considering that E2 the concentration-time profile after vaginal administration | — |
Countries
Netherlands
Outcome results
None listed