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

Overview

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.

Full Title of Study: “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.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Basic Science
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2011

Interventions

  • Drug: 91-day Levonorgestrel Oral Contraceptive
    • 91-day treatment consisting of 84 blue combination tablets containing 150 µg LNG/30 µg EE and 7 yellow tablets containing 10 µg EE.
  • Drug: 28-day Levonorgestrel Oral Contraceptive
    • 21 combination tablets containing 150 µg LNG/30 µg EE.
  • Drug: 28-day Desogestrel Oral Contraceptive
    • 21 combination tablets containing 150 µg DSG/30 µg EE.

Arms, Groups and Cohorts

  • Experimental: 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.
  • Active Comparator: 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.
  • Active Comparator: 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.

Clinical Trial Outcome Measures

Primary Measures

  • Change From Baseline to End of Month 6 in Prothrombin Fragment 1+2 Levels
    • Time Frame: 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 Measures

  • Change From Baseline to End of Month 6 in D-dimer
    • Time Frame: 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
    • Time Frame: 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)
    • Time Frame: 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)
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: Baseline to Month 6
    • Plasminogen is the precursor of plasmin, which lyses fibrin clots.
  • Change From Baseline to End of Month 6 in Tissue Plasminogen Activator (t-PA)
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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 Antithrombin
    • Time Frame: 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
    • Time Frame: 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 Protein C Antigen
    • Time Frame: 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
    • Time Frame: 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 Total Protein S
    • Time Frame: 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)
    • Time Frame: 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)
    • Time Frame: Baseline top Month 6
  • Change From Baseline to End of Month 6 in Total Cortisol
    • Time Frame: Baseline to Month 6
  • Change From Baseline to End of Month 6 in Corticosteroid Binding Globulin
    • Time Frame: Baseline to Month 6
  • Change From Baseline to End of Month 6 in Sex Hormone Binding Globulin (SHBG)
    • Time Frame: Baseline to Month 6

Participating in This Clinical Trial

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

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: 40 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Teva Women’s Health
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Teva Women’s Health Research Protocol Chair, Study Chair, Teva Women’s Health Research

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