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

Phase 2

Completed

Conditions: Oral Contraceptive
Hemostasis

Interventions: Drug: 28-day Levonorgestrel Oral Contraceptive
Drug: 91-day Levonorgestrel Oral Contraceptive
Drug: 28-day Desogestrel Oral Contraceptive

Registration Number: NCT01252186

Lead Sponsor: Teva Women's Health

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 265

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
28-day Levonorgestrel Oral Contraceptive	28-day Levonorgestrel Oral Contraceptive	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.
91-day Levonorgestrel Oral Contraceptive	91-day Levonorgestrel Oral Contraceptive	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.
28-day Desogestrel Oral Contraceptive	28-day Desogestrel Oral Contraceptive	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline to End of Month 6 in Prothrombin Fragment 1+2 Levels	Baseline to Month 6	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to End of Month 6 in Protein C Antigen	Baseline to Month 6	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.
Change From Baseline to End of Month 6 in Free Protein S	Baseline to Month 6	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.
Change From Baseline to End of Month 6 in Tissue Plasminogen Activator (t-PA)	Baseline to Month 6	Tissue plasminogen activator catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for the breakdown of blood clots.
Change From Baseline to End of Month 6 in Factor II	Baseline to Month 6	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.
Change From Baseline to End of Month 6 in Factor VII	Baseline to Month 6	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.
Change From Baseline to End of Month 6 in Factor VIII	Baseline to Month 6	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.
Change From Baseline to End of Month 6 in D-dimer	Baseline to Month 6	D-dimer is the degradation product of cross-linked fibrin and is a marker of thrombin and fibrin formation and turnover.
Change From Baseline to End of Month 6 in Plasmin-Antiplasmin (PAP) Complex	Baseline to Month 6	The plasmin-antiplasmin (PAP) complex is a marker of thrombin and fibrin formation and turnover.
Change From Baseline to End of Month 6 in Activated Partial Thromboplastin Time (APTT) Based Activated Protein-C Resistance (APC)	Baseline to Month 6	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.
Change From Baseline to End of Month 6 in Endogenous Thrombin Potential (EPT) Based Activated Protein-C Resistance (APC)	Baseline to Month 6	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.
Change From Baseline to End of Month 6 in Fibrinogen	Baseline to Month 6	Fibrinogen (factor I) is a glycoprotein that helps in the formation of blood clots.
Change From Baseline to End of Month 6 in Plasminogen	Baseline to Month 6	Plasminogen is the precursor of plasmin, which lyses fibrin clots.
Change From Baseline to End of Month 6 in Antithrombin	Baseline to Month 6	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.
Change From Baseline to End of Month 6 in Protein C Activity	Baseline to Month 6	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.
Change From Baseline to End of Month 6 in Total Protein S	Baseline to Month 6	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.
Change From Baseline to End of Month 6 in Tissue Factor Pathway Inhibitor (TFPI)	Baseline to Month 6	Tissue Factor Pathway Inhibitor (TFPI) is an anti-coagulation protein that binds to activated protein X.
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