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

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.

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.

Study Overview

• Status: Completed
• Conditions: Oral Contraceptive; Hemostasis
• Intervention / Treatment: Drug: 91-day Levonorgestrel Oral Contraceptive; Drug: 28-day Levonorgestrel Oral Contraceptive; Drug: 28-day Desogestrel Oral Contraceptive

• Study Type: Interventional
• Enrollment (Actual): 265
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Cagliari, Italy, 09124
    • Teva Investigational Site
  • Modena, Italy, 41100
    • Teva Investigational Site
  • Pavia, Italy, 27100
    • Teva Investigational Site
• United States
  • California
    • San Diego, California, United States, 92103
      • Teva Investigational Site
    • San Diego, California, United States, 92108
      • Teva Investigational Site
    • San Diego, California, United States, 92123
      • Teva Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20036
      • Teva Investigational Site
  • Florida
    • Miami, Florida, United States, 33186
      • Teva Investigational Site
    • West Palm Beach, Florida, United States, 33409
      • Teva Investigational Site
  • Georgia
    • Sandy Springs, Georgia, United States, 30328
      • Teva Investigational Site
  • New Jersey
    • Edison, New Jersey, United States, 08817
      • Teva Investigational Site
    • Plainsboro, New Jersey, United States, 08536
      • Teva Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Teva Investigational Site
  • New York
    • Port Jefferson, New York, United States, 11777
      • Teva Investigational Site
    • Rochester, New York, United States, 14609
      • Teva Investigational Site
  • North Carolina
    • Winston Salem, North Carolina, United States, 27103
      • Teva Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
      • Teva Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15206
      • Teva Investigational Site
    • Uniontown, Pennsylvania, United States, 15401
      • Teva Investigational Site
  • Texas
    • Dallas, Texas, United States, 75234
      • Teva Investigational Site
    • Houston, Texas, United States, 77054
      • Teva Investigational Site
    • San Antonio, Texas, United States, 78258
      • Teva Investigational Site
  • Virginia
    • Richmond, Virginia, United States, 23233
      • Teva Investigational Site
  • Washington
    • Seattle, Washington, United States, 98105
      • Teva Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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.; Other Names: Seasonique®
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.	Drug: 28-day Levonorgestrel Oral Contraceptive; 21 combination tablets containing 150 µg LNG/30 µg EE.; Other Names: Minidril®
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.	Drug: 28-day Desogestrel Oral Contraceptive; 21 combination tablets containing 150 µg DSG/30 µg EE.; Other Names: Marvelon®

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Teva Women's Health
• Investigators: Study Chair: Teva Women's Health Research Protocol Chair, Teva Women's Health Research

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: November 30, 2010
• First Submitted That Met QC Criteria: November 30, 2010
• First Posted (Estimate): December 2, 2010

Study Record Updates

• Last Update Posted (Estimate): March 13, 2015
• Last Update Submitted That Met QC Criteria: February 27, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: Contraception; Hemostasis; Blood Coagulation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Contraceptive Agents, Hormonal; Reproductive Control Agents; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Progestins; Levonorgestrel; Contraceptive Agents; Contraceptives, Oral; Desogestrel
• Other Study ID Numbers: PSE-HSP-203; 2010-023215-34 (EudraCT Number)