A Multicenter Study to Evaluate the Effects of a 91-Day Extended Cycle Oral Contraceptive on Hemostatic Parameters in Healthy Women

Study Overview
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Brief Summary
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This study is being conducted to evaluate the impact of a 91-day extended cycle oral contraceptive compared to two 28-day oral contraceptive regimens on hemostatic parameters in healthy women.

Official Title
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A Multinational, Multicenter, Randomized, Open-Label Study to Evaluate the Impact of a 91-Day Extended Cycle Oral Contraceptive Regimen, Compared to Two 28-day Standard Oral Contraceptive Regimens, on Hemostatic Parameters in Healthy Women.

Conditions
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Hemostasis, Oral Contraceptive

Intervention / Treatment
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* Drug: 91-day Levonorgestrel Oral Contraceptive
* Drug: 28-day Levonorgestrel Oral Contraceptive
* Drug: 28-day Desogestrel Oral Contraceptive


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Premenopausal, non-pregnant, non-lactating women age 18-40 years old Body Mass Index (BMI) ≥18 kg/m² and <30 kg/m² Regular spontaneous menstrual cycle Others as dictated by FDA-approved protocol Exclusion Criteria: Any condition which contraindicates the use of combination oral contraceptives Any history of, or active, deep vein thrombosis, pulmonary embolism, or arterial thromboembolic disease within one year of screening Any known genetic component for thrombophilia including Factor V Leiden mutation, prothrombin mutation, protein C deficiency, protein S deficience, or antithrombin III deficiency Others as dictated by FDA-approved protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 91-day Levonorgestrel Oral Contraceptive<br>Participants received 12 weeks (84 consecutive days) of active combination tablets containing 150 µg levonorgestrel (LNG)/30 µg ethinyl estradiol (EE), followed by 7 days of 10 µg EE monotherapy in each 91-day cycle for a total of two 91-day cycles. | Drug: 91-day Levonorgestrel Oral Contraceptive<br>* 91-day treatment consisting of 84 blue combination tablets containing 150 µg LNG/30 µg EE and 7 yellow tablets containing 10 µg EE.<br>* Other names: Seasonique®;|
| Active Comparator: 28-day Levonorgestrel Oral Contraceptive<br>Participants received 21 days of active combination tablets containing 150 µg LNG/30 µg EE, followed by no treatment for 7 days in each 28-day cycle for a total of six 28-day cycles. | Drug: 28-day Levonorgestrel Oral Contraceptive<br>* 21 combination tablets containing 150 µg LNG/30 µg EE.<br>* Other names: Minidril®;|
| Active Comparator: 28-day Desogestrel Oral Contraceptive<br>Participants received 21 days of active combination tablets (containing 150 µg desogestrel (DSG)/30 µg EE, followed by no treatment for 7 days in each 28-day cycle for a total of six 28-day cycles. | Drug: 28-day Desogestrel Oral Contraceptive<br>* 21 combination tablets containing 150 µg DSG/30 µg EE.<br>* Other names: Marvelon®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to End of Month 6 in Prothrombin Fragment 1+2 Levels | Prothrombin fragment 1+2 is a coagulation factor, released when prothrombin is cleaved by activated factor X. Elevated plasma levels of prothrombin fragment 1+2 indicate high risk of thrombosis. | Baseline to Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to End of Month 6 in D-dimer | D-dimer is the degradation product of cross-linked fibrin and is a marker of thrombin and fibrin formation and turnover. | Baseline to Month 6 | 
| Change From Baseline to End of Month 6 in Plasmin-Antiplasmin (PAP) Complex | The plasmin-antiplasmin (PAP) complex is a marker of thrombin and fibrin formation and turnover. | Baseline to Month 6 | 
| Change From Baseline to End of Month 6 in Activated Partial Thromboplastin Time (APTT) Based Activated Protein-C Resistance (APC) | The APC resistance assay is a clotting test that measures the ratio of APTT clotting times in the presence and absence of a standard amount of exogenous APC. APC resistance is calculated as the ratio of the clotting time after APC addition over the clotting time with no APC addition. APC resistance is defined as a poor anticoagulant response of plasma to APC (minimal prolongation of the APTT) and a correspondingly low ratio. | Baseline to Month 6 | 
| Change From Baseline to End of Month 6 in Endogenous Thrombin Potential (EPT) Based Activated Protein-C Resistance (APC) | This assay is based on measurement of the effect of activated protein C on the endogenous thrombin potential, the time integral of thrombin generation initiated in plasma through the extrinsic coagulation pathway. The APC resistance assay measures the ratio of endogenous thrombin potential in the presence and absence of a standard amount of exogenous APC. APC resistance is calculated as the ratio of EPT after APC addition over the EPT with no APC addition. APC resistance is defined as a poor anticoagulant response of plasma to APC (less inhibition of thrombin formation) and a correspondingly higher ratio. | Baseline to Month 6 | 
| Change From Baseline to End of Month 6 in Fibrinogen | Fibrinogen (factor I) is a glycoprotein that helps in the formation of blood clots. | Baseline to Month 6 | 
| Change From Baseline to End of Month 6 in Plasminogen | Plasminogen is the precursor of plasmin, which lyses fibrin clots. | Baseline to Month 6 | 
| Change From Baseline to End of Month 6 in Tissue Plasminogen Activator (t-PA) | Tissue plasminogen activator catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for the breakdown of blood clots. | Baseline to Month 6 | 
| Change From Baseline to End of Month 6 in Factor II | Clotting factor II, also called prothrombin, functions in blood coagulation. Results are reported as percent of normal plasma concentrations. By definition, normal plasma contains 100% (1 unit/mL) of each factor. The reference range is approximately 60% to 140% for adults. | Baseline to Month 6 | 
| Change From Baseline to End of Month 6 in Factor VII | Clotting factor VII, also called proconvertin or autoprothrombin I, functions in blood coagulation. Results are reported as percent of normal plasma concentrations. By definition, normal plasma contains 100% (1 unit/mL) of each factor. The reference range is approximately 60% to 140% for adults. | Baseline to Month 6 | 
| Change From Baseline to End of Month 6 in Factor VIII | Clotting factor VIII, also known as anti-hemophilic factor (AHF), functions in blood coagulation by stabilizing fibrin clots. Results are reported as a percent of the amount expected in normal plasma. By definition, the mean value in normal plasma is 100%. The reference range is approximately 70% to 140%.for adults. | Baseline to Month 6 | 
| Change From Baseline to End of Month 6 in Antithrombin | Antithrombin is a protein in the blood that naturally blocks blood clots from forming. Results are reported as a percent of the amount expected in normal plasma. By definition, the mean value in normal plasma is 100%. The reference range is approximately 80% to 130%.for adults. | Baseline to Month 6 | 
| Change From Baseline to End of Month 6 in Protein C Activity | Protein C helps to regulate blood clot formation. Activated Protein C (APC) combines with Protein S (a cofactor) to degrade coagulation factors VIIIa and Va, slowing down the generation of new thrombin and inhibiting further clotting. Results are reported as a percent of the amount expected in normal plasma. By definition, the mean value in normal plasma is 100%. The reference range is approximately 70% to 140% for adults. | Baseline to Month 6 | 
| Change From Baseline to End of Month 6 in Protein C Antigen | Protein C helps to regulate blood clot formation. Activated Protein C (APC) combines with Protein S (a cofactor) to degrade coagulation factors VIIIa and Va, slowing down the generation of new thrombin and inhibiting further clotting. Results are reported as a percent of the amount expected in normal plasma. By definition, the mean value in normal plasma is 100%. The reference range is approximately 70% to 140% in adults. | Baseline to Month 6 | 
| Change From Baseline to End of Month 6 in Free Protein S | Protein S helps to regulate blood clot formation. Protein S exists in two forms: a free form and a complex form. Free protein S combines with Protein C to degrade coagulation factors VIIIa and Va, slowing down the generation of new thrombin and inhibiting further clotting. Results are reported as a percent of the amount expected in normal plasma. By definition, the mean value in normal plasma is 100%. The reference range is approximately 70% to 140%; lower for women than for men. | Baseline to Month 6 | 
| Change From Baseline to End of Month 6 in Total Protein S | Protein S helps to regulate blood clot formation. Protein S exists in two forms: a free form and a complex form. Free protein S combines with activated protein C to degrade coagulation factors VIIIa and Va, slowing down the generation of new thrombin and inhibiting further clotting. Results are reported as a percent of the amount expected in normal plasma. By definition, the mean value in normal plasma is 100%. The reference range is approximately 70% to 140%; lower for women than for men. | Baseline to Month 6 | 
| Change From Baseline to End of Month 6 in Tissue Factor Pathway Inhibitor (TFPI) | Tissue Factor Pathway Inhibitor (TFPI) is an anti-coagulation protein that binds to activated protein X. | Baseline to Month 6 | 
| Change From Baseline to End of Month 6 in Thyroid Stimulating Hormone (TSH) |  | Baseline top Month 6 | 
| Change From Baseline to End of Month 6 in Total Cortisol |  | Baseline to Month 6 | 
| Change From Baseline to End of Month 6 in Corticosteroid Binding Globulin |  | Baseline to Month 6 | 
| Change From Baseline to End of Month 6 in Sex Hormone Binding Globulin (SHBG) |  | Baseline to Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Contraception, Hemostasis, Blood Coagulation