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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Women's Health )
ClinicalTrials.gov Identifier:
NCT01252186
First received: November 30, 2010
Last updated: February 27, 2015
Last verified: February 2015
  Purpose

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.


Condition Intervention Phase
Hemostasis
Oral Contraceptive
Drug: 91-day Levonorgestrel Oral Contraceptive
Drug: 28-day Levonorgestrel Oral Contraceptive
Drug: 28-day Desogestrel Oral Contraceptive
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • Change From Baseline to End of Month 6 in Prothrombin Fragment 1+2 Levels [ Time Frame: Baseline to Month 6 ] [ Designated as safety issue: Yes ]
    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:
  • Change From Baseline to End of Month 6 in D-dimer [ Time Frame: Baseline to Month 6 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Change From Baseline to End of Month 6 in Total Cortisol [ Time Frame: Baseline to Month 6 ] [ Designated as safety issue: No ]
  • Change From Baseline to End of Month 6 in Corticosteroid Binding Globulin [ Time Frame: Baseline to Month 6 ] [ Designated as safety issue: No ]
  • Change From Baseline to End of Month 6 in Sex Hormone Binding Globulin (SHBG) [ Time Frame: Baseline to Month 6 ] [ Designated as safety issue: No ]

Enrollment: 265
Study Start Date: November 2010
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: Marvelon®

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01252186

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

No publications provided

Responsible Party: Teva Pharmaceutical Industries ( Teva Women's Health )
ClinicalTrials.gov Identifier: NCT01252186     History of Changes
Other Study ID Numbers: PSE-HSP-203, 2010-023215-34
Study First Received: November 30, 2010
Results First Received: February 27, 2015
Last Updated: February 27, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Teva Pharmaceutical Industries:
Contraception
Hemostasis
Blood Coagulation

Additional relevant MeSH terms:
Contraceptive Agents
Contraceptives, Oral
Desogestrel
Hemostatics
Levonorgestrel
Coagulants
Contraceptive Agents, Female
Contraceptives, Oral, Synthetic
Hematologic Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Progestins
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 28, 2015