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

Hemostasis Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01252186
• Other study ID #: PSE-HSP-203
• Secondary ID: 2010-023215-34
• Status: Completed
• Phase: Phase 2
• First received: November 30, 2010
• Last updated: February 27, 2015
• Start date: November 2010
• Est. completion date: December 2011

Study information

• Verified date: February 2015
• Source: Teva Pharmaceutical Industries
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 265
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Hemostasis
• Oral Contraceptive

Intervention

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.
• 28-day Levonorgestrel Oral Contraceptive
21 combination tablets containing 150 µg LNG/30 µg EE.
• 28-day Desogestrel Oral Contraceptive
21 combination tablets containing 150 µg DSG/30 µg EE.

Locations

Country	Name	City	State
Italy	Teva Investigational Site	Cagliari
Italy	Teva Investigational Site	Modena
Italy	Teva Investigational Site	Pavia
United States	Teva Investigational Site	Albuquerque	New Mexico
United States	Teva Investigational Site	Dallas	Texas
United States	Teva Investigational Site	Edison	New Jersey
United States	Teva Investigational Site	Houston	Texas
United States	Teva Investigational Site	Miami	Florida
United States	Teva Investigational Site	Philadelphia	Pennsylvania
United States	Teva Investigational Site	Pittsburgh	Pennsylvania
United States	Teva Investigational Site	Plainsboro	New Jersey
United States	Teva Investigational Site	Port Jefferson	New York
United States	Teva Investigational Site	Richmond	Virginia
United States	Teva Investigational Site	Rochester	New York
United States	Teva Investigational Site	San Antonio	Texas
United States	Teva Investigational Site	San Diego	California
United States	Teva Investigational Site	San Diego	California
United States	Teva Investigational Site	San Diego	California
United States	Teva Investigational Site	Sandy Springs	Georgia
United States	Teva Investigational Site	Seattle	Washington
United States	Teva Investigational Site	Uniontown	Pennsylvania
United States	Teva Investigational Site	Washington	District of Columbia
United States	Teva Investigational Site	West Palm Beach	Florida
United States	Teva Investigational Site	Winston Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Teva Women's Health

Countries where clinical trial is conducted

United States,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	No
Secondary	Change From Baseline to End of Month 6 in Plasminogen	Plasminogen is the precursor of plasmin, which lyses fibrin clots.	Baseline to Month 6	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	No
Secondary	Change From Baseline to End of Month 6 in Thyroid Stimulating Hormone (TSH)		Baseline top Month 6	No
Secondary	Change From Baseline to End of Month 6 in Total Cortisol		Baseline to Month 6	No
Secondary	Change From Baseline to End of Month 6 in Corticosteroid Binding Globulin		Baseline to Month 6	No
Secondary	Change From Baseline to End of Month 6 in Sex Hormone Binding Globulin (SHBG)		Baseline to Month 6	No