Hemostasis, Oral Contraceptive
Conditions
Keywords
Contraception, Hemostasis, Blood Coagulation
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.
Interventions
91-day treatment consisting of 84 blue combination tablets containing 150 µg LNG/30 µg EE and 7 yellow tablets containing 10 µg EE.
21 combination tablets containing 150 µg LNG/30 µg EE.
DRUG28-day Desogestrel Oral Contraceptive
21 combination tablets containing 150 µg DSG/30 µg EE.
Sponsors
Teva Women's Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 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 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 | — |
| 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. |
Countries
Italy, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 75 |
| 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. | 80 |
| 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. | 71 |
| Total | 226 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 6 | 8 |
| Overall Study | Lost to Follow-up | 10 | 10 | 11 |
| Overall Study | Non-compliance | 0 | 3 | 4 |
| Overall Study | Other - Miscellaneous Reasons | 5 | 5 | 7 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Pregnancy | 2 | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Sponsor Request | 2 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 5 | 2 |
Baseline characteristics
| Characteristic | 91-day Levonorgestrel Oral Contraceptive | 28-day Levonorgestrel Oral Contraceptive | 28-day Desogestrel Oral Contraceptive | Total |
|---|---|---|---|---|
| Age, Continuous | 27.3 years STANDARD_DEVIATION 5.87 | 26.8 years STANDARD_DEVIATION 6.22 | 27.0 years STANDARD_DEVIATION 5.75 | 27.0 years STANDARD_DEVIATION 5.94 |
| Race/Ethnicity, Customized Asian | 1 participants | 5 participants | 3 participants | 9 participants |
| Race/Ethnicity, Customized Black or African-American | 18 participants | 15 participants | 9 participants | 42 participants |
| Race/Ethnicity, Customized Caucasian | 42 participants | 39 participants | 40 participants | 121 participants |
| Race/Ethnicity, Customized Hispanic | 13 participants | 20 participants | 19 participants | 52 participants |
| Race/Ethnicity, Customized Other | 1 participants | 1 participants | 0 participants | 2 participants |
| Sex: Female, Male Female | 75 Participants | 80 Participants | 71 Participants | 226 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 16 / 83 | 10 / 89 | 17 / 80 |
| serious Total, serious adverse events | 0 / 83 | 0 / 89 | 0 / 80 |
Outcome results
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.
Time frame: Baseline to Month 6
Population: Per-Protocol (PP) Population included all data from ITT participants obtained prior to experiencing major protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Prothrombin Fragment 1+2 Levels | 169.53 pmol/L | Standard Error 155.15 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Prothrombin Fragment 1+2 Levels | 157.99 pmol/L | Standard Error 150.11 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Prothrombin Fragment 1+2 Levels | 592.29 pmol/L | Standard Error 160.32 |
Comparison: The primary endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.95895% CI: [-440.1, 417]Mixed Models Analysis
Comparison: The primary endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.0695% CI: [-18.3, 863.8]Mixed Models Analysis
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.
Time frame: Baseline to Month 6
Population: Per-protocol population with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Activated Partial Thromboplastin Time (APTT) Based Activated Protein-C Resistance (APC) | -0.12 ratio | Standard Error 0.04 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Activated Partial Thromboplastin Time (APTT) Based Activated Protein-C Resistance (APC) | -0.15 ratio | Standard Error 0.03 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Activated Partial Thromboplastin Time (APTT) Based Activated Protein-C Resistance (APC) | -0.27 ratio | Standard Error 0.04 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.42895% CI: [-0.1, 0.1]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.00295% CI: [-0.3, -0.1]Mixed Models Analysis
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.
Time frame: Baseline to Month 6
Population: Per-protocol population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Antithrombin | 2.36 percentage of normal | Standard Error 1 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Antithrombin | -0.05 percentage of normal | Standard Error 0.98 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Antithrombin | -0.83 percentage of normal | Standard Error 1.03 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.08895% CI: [-5.2, 0.4]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.02895% CI: [-6, -0.3]Mixed Models Analysis
Secondary
Change From Baseline to End of Month 6 in Corticosteroid Binding Globulin
Time frame: Baseline to Month 6
Population: Per-protocol population with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Corticosteroid Binding Globulin | 576.33 nmol/L | Standard Error 45.37 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Corticosteroid Binding Globulin | 563.85 nmol/L | Standard Error 43.41 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Corticosteroid Binding Globulin | 634.64 nmol/L | Standard Error 46.74 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.84395% CI: [-136.4, 111.4]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.37695% CI: [-71.3, 187.9]Mixed Models Analysis
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.
Time frame: Baseline to Month 6
Population: Per-protocol population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in D-dimer | 86.74 ng/mL | Standard Error 31.49 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in D-dimer | 72.43 ng/mL | Standard Error 30.18 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in D-dimer | 158.05 ng/mL | Standard Error 32.07 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.74595% CI: [-100.8, 72.2]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.11595% CI: [-17.5, 160.1]Mixed Models Analysis
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.
Time frame: Baseline to Month 6
Population: Per-protocol population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Endogenous Thrombin Potential (EPT) Based Activated Protein-C Resistance (APC) | 0.38 ratio | Standard Error 0.05 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Endogenous Thrombin Potential (EPT) Based Activated Protein-C Resistance (APC) | 0.37 ratio | Standard Error 0.05 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Endogenous Thrombin Potential (EPT) Based Activated Protein-C Resistance (APC) | 0.57 ratio | Standard Error 0.05 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.86895% CI: [-0.2, 0.1]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.01295% CI: [0, 0.3]Mixed Models Analysis
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.
Time frame: Baseline to Month 6
Population: Per-protocol population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Factor II | 6.89 percentage of normal | Standard Error 1.73 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Factor II | 7.98 percentage of normal | Standard Error 1.65 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Factor II | 8.57 percentage of normal | Standard Error 1.76 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.64895% CI: [-3.6, 5.8]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.49695% CI: [-3.2, 6.6]Mixed Models Analysis
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.
Time frame: Baseline to Month 6
Population: Per-protocol population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Factor VII | 14.27 percentage of normal | Standard Error 7.52 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Factor VII | 22.98 percentage of normal | Standard Error 7.18 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Factor VII | 43.22 percentage of normal | Standard Error 7.67 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.40595% CI: [-11.9, 29.3]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.00895% CI: [7.7, 50.2]Mixed Models Analysis
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.
Time frame: Baseline to Month 6
Population: Per-protocol population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Factor VIII | -3.23 percentage of normal | Standard Error 2.98 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Factor VIII | 0.08 percentage of normal | Standard Error 2.87 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Factor VIII | 5.53 percentage of normal | Standard Error 3.05 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.425195% CI: [-4.9, 11.5]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.04195% CI: [0.3, 17.2]Mixed Models Analysis
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.
Time frame: Baseline to Month 6
Population: Per-protocol population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Fibrinogen | 0.12 g/L | Standard Error 0.07 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Fibrinogen | 0.22 g/L | Standard Error 0.06 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Fibrinogen | -0.04 g/L | Standard Error 0.07 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.31795% CI: [-0.1, 0.3]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.08195% CI: [-0.4, 0]Mixed Models Analysis
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.
Time frame: Baseline to Month 6
Population: Per-protocol population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Free Protein S | 2.96 percentage of normal | Standard Error 2.13 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Free Protein S | 4.62 percentage of normal | Standard Error 2.03 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Free Protein S | -18.2 percentage of normal | Standard Error 2.17 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.57295% CI: [-4.1, 7.5]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: <0.00195% CI: [-27, -15]Mixed Models Analysis
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.
Time frame: Baseline to Month 6
Population: Per-protocol population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Plasmin-Antiplasmin (PAP) Complex | 10.72 ng/mL | Standard Error 44.55 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Plasmin-Antiplasmin (PAP) Complex | -6.42 ng/mL | Standard Error 43.11 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Plasmin-Antiplasmin (PAP) Complex | 107.81 ng/mL | Standard Error 45.97 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.78295% CI: [-139.4, 105.1]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.13195% CI: [-29.2, 223.4]Mixed Models Analysis
Secondary
Change From Baseline to End of Month 6 in Plasminogen
Plasminogen is the precursor of plasmin, which lyses fibrin clots.
Time frame: Baseline to Month 6
Population: Per-protocol population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Plasminogen | 0.04 g/L | Standard Error 0 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Plasminogen | 0.04 g/L | Standard Error 0 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Plasminogen | 0.04 g/L | Standard Error 0 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.33195% CI: [-0.013, 0.004]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.17395% CI: [-0.015, 0.003]Mixed Models Analysis
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.
Time frame: Baseline to Month 6
Population: Per-protocol population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Protein C Activity | -6.15 percentage of normal | Standard Error 2.62 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Protein C Activity | -4.39 percentage of normal | Standard Error 2.53 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Protein C Activity | -2.41 percentage of normal | Standard Error 2.7 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.63195% CI: [-5.4, 8.9]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.32395% CI: [-3.7, 11.2]Mixed Models Analysis
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.
Time frame: Baseline to Month 6
Population: Per-protocol population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Protein C Antigen | 12.83 percentage of normal | Standard Error 2.26 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Protein C Antigen | 11.97 percentage of normal | Standard Error 2.17 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Protein C Antigen | 10.00 percentage of normal | Standard Error 2.32 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.783595% CI: [-7, 5.3]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.38495% CI: [-9.2, 3.6]Mixed Models Analysis
Secondary
Change From Baseline to End of Month 6 in Sex Hormone Binding Globulin (SHBG)
Time frame: Baseline to Month 6
Population: Per-protocol population with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Sex Hormone Binding Globulin (SHBG) | 34.87 mIU/L | Standard Error 8.4 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Sex Hormone Binding Globulin (SHBG) | 30.85 mIU/L | Standard Error 8.08 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Sex Hormone Binding Globulin (SHBG) | 165.01 mIU/L | Standard Error 8.67 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.73195% CI: [-27, 19]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: <0.00195% CI: [106.2, 154.1]Mixed Models Analysis
Secondary
Change From Baseline to End of Month 6 in Thyroid Stimulating Hormone (TSH)
Time frame: Baseline top Month 6
Population: Per-protocol population with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Thyroid Stimulating Hormone (TSH) | -0.22 mIU/L | Standard Error 0.13 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Thyroid Stimulating Hormone (TSH) | 0.10 mIU/L | Standard Error 0.13 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Thyroid Stimulating Hormone (TSH) | 0.22 mIU/L | Standard Error 0.13 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.07695% CI: [0, 0.7]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.02195% CI: [0.1, 0.8]Mixed Models Analysis
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.
Time frame: Baseline to Month 6
Population: Per-protocol population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Tissue Factor Pathway Inhibitor (TFPI) | 4.65 ng/mL | Standard Error 1.26 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Tissue Factor Pathway Inhibitor (TFPI) | 2.54 ng/mL | Standard Error 1.21 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Tissue Factor Pathway Inhibitor (TFPI) | -1.34 ng/mL | Standard Error 1.3 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.22795% CI: [-5.6, 1.3]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.00195% CI: [-9.6, -2.4]Mixed Models Analysis
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.
Time frame: Baseline to Month 6
Population: Per-protocol population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Tissue Plasminogen Activator (t-PA) | -0.91 µg/L | Standard Error 0.32 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Tissue Plasminogen Activator (t-PA) | -1.48 µg/L | Standard Error 0.3 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Tissue Plasminogen Activator (t-PA) | -9.3 µg/L | Standard Error 0.32 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.19495% CI: [-1.4, 0.3]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.96795% CI: [-0.9, 0.9]Mixed Models Analysis
Secondary
Change From Baseline to End of Month 6 in Total Cortisol
Time frame: Baseline to Month 6
Population: Per-protocol population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Total Cortisol | 217.94 nmol/L | Standard Error 24.39 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Total Cortisol | 262.40 nmol/L | Standard Error 23.39 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Total Cortisol | 227.68 nmol/L | Standard Error 24.96 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.1995% CI: [-22.3, 111.2]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.78195% CI: [-59.4, 78.9]Mixed Models Analysis
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.
Time frame: Baseline to Month 6
Population: Per-protocol population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Total Protein S | -11.06 percentage of normal | Standard Error 1.51 |
| 28-day Levonorgestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Total Protein S | -11.48 percentage of normal | Standard Error 1.45 |
| 28-day Desogestrel Oral Contraceptive | Change From Baseline to End of Month 6 in Total Protein S | -21.59 percentage of normal | Standard Error 1.55 |
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: 0.84195% CI: [-4.6, 3.7]Mixed Models Analysis
Comparison: The endpoint was analyzed using a maximum likelihood-based mixed model repeated measures (MMRM) analysis of covariance (ANCOVA) with covariate adjustment for baseline, treatment, month, and the treatment-by-month interaction.p-value: <0.00195% CI: [-14.8, -6.3]Mixed Models Analysis