Hemostasis, Oral Contraceptive
Conditions
Keywords
Contraception, Hemostasis, Blood Coagulation
Brief summary
This study is being conducted to evaluate the impact of DR-102, a 28-day oral contraceptive compared to a standard 28-day oral contraceptive regimen on hemostatic parameters in healthy women.
Interventions
DRUGdesogestrel/ethinyl estradiol
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
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 * Thrombophlebitis or thromboembolic disorders; known or suspected clotting disorders; thrombogenetic valvulopathies or rhythm disorders * Others as dictated by FDA-approved protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Prothrombin Fragment 1 + 2 Levels | Baseline through Month 6 | Normal range for this hemostatic parameter was 41 to 372 pmol/L. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean Change From Baseline Over the 6-Month Period in Protein S Total Antigen | Baseline through Month 6 | The normal range for this hemostatic parameter was 50% to 147%. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction. |
| Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Protein C Activity | Baseline through Month 6 | The normal range for this hemostatic parameter was 70% to 180%. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction. |
| Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Antithrombin | Baseline through Month 6 | Normal range for this hemostatic parameter was 75% to 130%. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction. |
| Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Factor II Activity | Baseline through Month 6 | Normal range for this hemostatic parameter was 70% to 150%. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction. |
| Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Factor VII | Baseline through Month 6 | Normal range for this hemostatic parameter was 60% to 150%. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction. |
| Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Factor VIII | Baseline through Month 6 | Normal range for this hemostatic parameter was 50% to 180%. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction. |
| Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in D-Dimer | Baseline through Month 6 | Normal range for this hemostatic parameter was 0 to 729 mcg/L. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction. |
| Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Endogenous Thrombin Potential (EPT)-Based Activated Protein-C (APC) Resistance | Baseline through Month 6 | This hemostatic parameter is calculated by dividing the clotting time with APC by the clotting time without APC. Normal range for this measure was defined as a ratio of 0.32 to 1.79. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction. |
| Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Corticosteroid-Binding Globulin | Baseline through Month 6 | Normal range for this adrenal parameter was 1906.448 to 4520.504 mg/L. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction. |
| Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Serum Random Total Cortisol | Baseline through Month 6 | Normal range for this adrenal parameter was 85.6 to 618.2 nmol/L. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction. |
| Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Thyroid-Stimulating Hormone (TSH) | Baseline through Month 6 | Normal range for this parameter was 0.35 to 5.5 mIU/L. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction. |
| Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Sex Hormone Binding Globulin | Baseline through Month 6 | Normal range for this parameter was 28 to 146 nmol/L. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction. |
| Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Activated Partial Thromboplastin Time (APTT)-Based Activated Protein-C (APC) Resistance | Baseline through Month 6 | This hemostatic parameter is calculated by dividing the clotting time with APC by the clotting time without APC. Normal range for this measure was defined as a ratio of 2.00 to 3.36. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction. |
Countries
Germany, Israel, Italy, Spain
Participant flow
Recruitment details
Of the 351 healthy women screened for enrollment, 293 at 26 centers in the European Union (EU) (21 centers) and Israel (5 centers) met entry criteria and were considered to be eligible for this study.
Pre-assignment details
Of the 58 women who were screened but not randomly assigned to receive treatment, 10 were excluded on the basis of inclusion/exclusion criteria, 32 withdrew consent, and 6 were lost to follow-up before the baseline visit. An additional 10 participants were not randomly assigned to treatment for other reasons.
Participants by arm
| Arm | Count |
|---|---|
| Treatment I: (DR-102) 21 days of combination active pills (containing 150 mcg desogestrel \[DSG\]/20 mcg ethinyl estradiol \[EE\]), followed by 7 days of 10 mcg EE, taken orally for 6 consecutive 28-day cycles | 145 |
| Treatment II 21 days combination active pills (containing 150 mcg DSG/20 mcg EE), taken orally and followed by 7 days of no treatment for a total of 6 consecutive 28-day cycles | 142 |
| Total | 287 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 9 |
| Overall Study | Lost to Follow-up | 4 | 3 |
| Overall Study | Noncompliance | 2 | 0 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Sponsor Request | 9 | 7 |
| Overall Study | Withdrawal by Subject | 6 | 10 |
Baseline characteristics
| Characteristic | Treatment I: (DR-102) | Treatment II | Total |
|---|---|---|---|
| Age, Continuous | 26.4 years STANDARD_DEVIATION 4.98 | 27.0 years STANDARD_DEVIATION 5.26 | 26.7 years STANDARD_DEVIATION 5.12 |
| Body Mass Index (BMI) | 22.9 kg/m^2 STANDARD_DEVIATION 3.62 | 22.4 kg/m^2 STANDARD_DEVIATION 3.06 | 22.6 kg/m^2 STANDARD_DEVIATION 3.36 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Other | 4 participants | 3 participants | 7 participants |
| Race/Ethnicity, Customized White | 140 participants | 136 participants | 276 participants |
| Sex: Female, Male Female | 145 Participants | 142 Participants | 287 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Weight | 61.6 kg STANDARD_DEVIATION 10.35 | 60.1 kg STANDARD_DEVIATION 9.36 | 60.9 kg STANDARD_DEVIATION 9.89 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 84 / 145 | 66 / 142 |
| serious Total, serious adverse events | 0 / 145 | 1 / 142 |
Outcome results
Primary
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Prothrombin Fragment 1 + 2 Levels
Normal range for this hemostatic parameter was 41 to 372 pmol/L. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.
Time frame: Baseline through Month 6
Population: Per-protocol (PP) population. PP population included all data from intent-to-treat (ITT) participants obtained prior to any major protocol violations. PP participants were analyzed according to the treatment actually received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment I: (DR-102) | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Prothrombin Fragment 1 + 2 Levels | 45.0 pmol/L | Standard Error 15.24 |
| Treatment II | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Prothrombin Fragment 1 + 2 Levels | 56.8 pmol/L | Standard Error 15.6 |
p-value: 0.589295% CI: [-54.75, 31.17]ANCOVA
Secondary
Least Squares Mean Change From Baseline Over the 6-Month Period in Protein S Total Antigen
The normal range for this hemostatic parameter was 50% to 147%. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.
Time frame: Baseline through Month 6
Population: Per protocol (PP) population with BL and at least 1 post-BL value for this measurement. PP population included all data from intent-to-treat (ITT) participants obtained prior to any major protocol violations. PP participants were analyzed according to the treatment actually received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment I: (DR-102) | Least Squares Mean Change From Baseline Over the 6-Month Period in Protein S Total Antigen | -11.4 percentage of normal 50% to 147% | Standard Error 1.09 |
| Treatment II | Least Squares Mean Change From Baseline Over the 6-Month Period in Protein S Total Antigen | -6.6 percentage of normal 50% to 147% | Standard Error 1.1 |
p-value: 0.002195% CI: [-7.87, -1.77]ANCOVA
Secondary
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Activated Partial Thromboplastin Time (APTT)-Based Activated Protein-C (APC) Resistance
This hemostatic parameter is calculated by dividing the clotting time with APC by the clotting time without APC. Normal range for this measure was defined as a ratio of 2.00 to 3.36. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.
Time frame: Baseline through Month 6
Population: Per protocol (PP) population with BL and at least 1 post-BL value for this measurement. PP population included all data from intent-to-treat (ITT) participants obtained prior to any major protocol violations. PP participants were analyzed according to the treatment actually received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment I: (DR-102) | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Activated Partial Thromboplastin Time (APTT)-Based Activated Protein-C (APC) Resistance | -0.3 ratio | Standard Error 0.02 |
| Treatment II | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Activated Partial Thromboplastin Time (APTT)-Based Activated Protein-C (APC) Resistance | -0.4 ratio | Standard Error 0.02 |
p-value: 0.045995% CI: [0, 0.14]ANCOVA
Secondary
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Antithrombin
Normal range for this hemostatic parameter was 75% to 130%. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.
Time frame: Baseline through Month 6
Population: Per protocol (PP) population with BL and at least 1 post-BL value for this measurement. PP population included all data from intent-to-treat (ITT) participants obtained prior to any major protocol violations. PP participants were analyzed according to the treatment actually received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment I: (DR-102) | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Antithrombin | -1.6 percentage of normal | Standard Error 1.17 |
| Treatment II | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Antithrombin | -3.2 percentage of normal | Standard Error 1.18 |
p-value: 0.34495% CI: [-1.7, 4.85]ANCOVA
Secondary
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Corticosteroid-Binding Globulin
Normal range for this adrenal parameter was 1906.448 to 4520.504 mg/L. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.
Time frame: Baseline through Month 6
Population: Per protocol (PP) population with BL and at least 1 post-BL value for this measurement. PP population included all data from intent-to-treat (ITT) participants obtained prior to any major protocol violations. PP participants were analyzed according to the treatment actually received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment I: (DR-102) | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Corticosteroid-Binding Globulin | 4083.3 mg/L | Standard Error 159.45 |
| Treatment II | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Corticosteroid-Binding Globulin | 3721.8 mg/L | Standard Error 162.95 |
p-value: 0.114895% CI: [-88.45, 811.61]ANCOVA
Secondary
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in D-Dimer
Normal range for this hemostatic parameter was 0 to 729 mcg/L. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.
Time frame: Baseline through Month 6
Population: Per protocol (PP) population with BL and at least 1 post-BL value for this measurement. PP population included all data from intent-to-treat (ITT) participants obtained prior to any major protocol violations. PP participants were analyzed according to the treatment actually received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment I: (DR-102) | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in D-Dimer | 16.4 mcg/L | Standard Error 10.29 |
| Treatment II | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in D-Dimer | 13.4 mcg/L | Standard Error 10.46 |
p-value: 0.83995% CI: [-25.96, 31.94]ANCOVA
Secondary
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Endogenous Thrombin Potential (EPT)-Based Activated Protein-C (APC) Resistance
This hemostatic parameter is calculated by dividing the clotting time with APC by the clotting time without APC. Normal range for this measure was defined as a ratio of 0.32 to 1.79. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.
Time frame: Baseline through Month 6
Population: Per protocol (PP) population with BL and at least 1 post-BL value for this measurement. PP population included all data from intent-to-treat (ITT) participants obtained prior to any major protocol violations. PP participants were analyzed according to the treatment actually received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment I: (DR-102) | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Endogenous Thrombin Potential (EPT)-Based Activated Protein-C (APC) Resistance | 0.8 ratio | Standard Error 0.04 |
| Treatment II | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Endogenous Thrombin Potential (EPT)-Based Activated Protein-C (APC) Resistance | 0.7 ratio | Standard Error 0.04 |
p-value: 0.031895% CI: [0.01, 0.26]ANCOVA
Secondary
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Factor II Activity
Normal range for this hemostatic parameter was 70% to 150%. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.
Time frame: Baseline through Month 6
Population: Per protocol (PP) population with BL and at least 1 post-BL value for this measurement. PP population included all data from intent-to-treat (ITT) participants obtained prior to any major protocol violations. PP participants were analyzed according to the treatment actually received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment I: (DR-102) | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Factor II Activity | 3.3 percentage of normal | Standard Error 0.21 |
| Treatment II | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Factor II Activity | 3.0 percentage of normal | Standard Error 0.21 |
p-value: 0.252295% CI: [-0.24, 0.92]ANCOVA
Secondary
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Factor VII
Normal range for this hemostatic parameter was 60% to 150%. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.
Time frame: Baseline through Month 6
Population: Per protocol (PP) population with BL and at least 1 post-BL value for this measurement. PP population included all data from intent-to-treat (ITT) participants obtained prior to any major protocol violations. PP participants were analyzed according to the treatment actually received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment I: (DR-102) | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Factor VII | 17.9 percentage of normal | Standard Error 0.81 |
| Treatment II | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Factor VII | 15.1 percentage of normal | Standard Error 0.82 |
p-value: 0.014395% CI: [0.58, 5.13]ANCOVA
Secondary
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Factor VIII
Normal range for this hemostatic parameter was 50% to 180%. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.
Time frame: Baseline through Month 6
Population: Per protocol (PP) population with BL and at least 1 post-BL value for this measurement. PP population included all data from intent-to-treat (ITT) participants obtained prior to any major protocol violations. PP participants were analyzed according to the treatment actually received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment I: (DR-102) | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Factor VIII | 11.1 percentage of normal | Standard Error 1.92 |
| Treatment II | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Factor VIII | 10.6 percentage of normal | Standard Error 1.95 |
p-value: 0.850795% CI: [-4.87, 5.91]ANCOVA
Secondary
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Protein C Activity
The normal range for this hemostatic parameter was 70% to 180%. Participants were in a fasting state and had refrained from moderate to vigorous exercise prior to phlebotomy on the day of this lab draw. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.
Time frame: Baseline through Month 6
Population: Per protocol (PP) population with BL and at least 1 post-BL value for this measurement. PP population included all data from intent-to-treat (ITT) participants obtained prior to any major protocol violations. PP participants were analyzed according to the treatment actually received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment I: (DR-102) | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Protein C Activity | 16.3 percentage of normal | Standard Error 1.9 |
| Treatment II | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Protein C Activity | 13.0 percentage of normal | Standard Error 1.93 |
p-value: 0.231295% CI: [-2.08, 8.58]ANCOVA
Secondary
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Serum Random Total Cortisol
Normal range for this adrenal parameter was 85.6 to 618.2 nmol/L. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.
Time frame: Baseline through Month 6
Population: Per protocol (PP) population with BL and at least 1 post-BL value for this measurement. PP population included all data from intent-to-treat (ITT) participants obtained prior to any major protocol violations. PP participants were analyzed according to the treatment actually received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment I: (DR-102) | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Serum Random Total Cortisol | 239.0 nmol/L | Standard Error 15.67 |
| Treatment II | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Serum Random Total Cortisol | 230.8 nmol/L | Standard Error 16.03 |
p-value: 0.713695% CI: [-35.92, 52.39]ANCOVA
Secondary
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Sex Hormone Binding Globulin
Normal range for this parameter was 28 to 146 nmol/L. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.
Time frame: Baseline through Month 6
Population: Per protocol (PP) population with BL and at least 1 post-BL value for this measurement. PP population included all data from intent-to-treat (ITT) participants obtained prior to any major protocol violations. PP participants were analyzed according to the treatment actually received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment I: (DR-102) | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Sex Hormone Binding Globulin | 163.4 nmol/L | Standard Error 7.29 |
| Treatment II | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Sex Hormone Binding Globulin | 149.1 nmol/L | Standard Error 7.46 |
p-value: 0.173195% CI: [-6.29, 34.8]ANCOVA
Secondary
Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Thyroid-Stimulating Hormone (TSH)
Normal range for this parameter was 0.35 to 5.5 mIU/L. Change from baseline was analyzed using a repeated measures analysis of covariance with covariate adjustment for baseline, treatment, month, and the treatment by month interaction.
Time frame: Baseline through Month 6
Population: Per protocol (PP) population with BL and at least 1 post-BL value for this measurement. PP population included all data from intent-to-treat (ITT) participants obtained prior to any major protocol violations. PP participants were analyzed according to the treatment actually received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment I: (DR-102) | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Thyroid-Stimulating Hormone (TSH) | 0.2 mIU/L | Standard Error 0.07 |
| Treatment II | Least Squares Mean Change From Baseline Over the 6-Month Treatment Period in Thyroid-Stimulating Hormone (TSH) | 0.3 mIU/L | Standard Error 0.07 |
p-value: 0.390395% CI: [-0.29, 0.11]ANCOVA