Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study was to determine and compare the rate and extent of absorption of norethindrone and unconjugated estradiol from a test formulation of Estradiol/Norethindrone Acetate Tablets, 1 mg/0.5 mg versus the reference Activella® (1 mg estradiol/0.5 mg norethindrone acetate) Tablets under fed conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA Bioequivalence Statistical Methods
Interventions
1 mg/0.5 mg Tablets
DRUGActivella®
1 mg/0.5 mg Tablets
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Non-smoking or smoking (up to 10 cigarettes/day), physiologically or surgically post-menopausal female within the age range of 18-65 years. * 17β-estradiol serum levels of ≤ 92 pmol/L and follicle-stimulating hormone (FSH) of ≥ 40 IU/L. * Body Mass Index (BMI) greater than or equal to 19.0 kg/m2 and less than or equal to 30.0 kg/m2. * Normal findings in the physical examination, 12-lead electrocardiogram (ECG) and vital signs. * Hemoglobin ≥ 115 g/L. * Normal pap smear. * Normal mammogram within 1 year for subjects who are over the age of 50 years. * Negative for drugs of abuse and alcohol. * Negative for hepatitis B-surface antigen, hepatitis C, and Human Immunodeficiency Virus (HIV). * No clinical laboratory values outside the acceptable range unless the Principal Investigator or Sub-Investigator decides that they are not clinically significant (NCS). * Negative for pregnancy. * Subjects who are surgically post-menopausal with an intact uterus (i.e. bilateral oophorectomy) for at least 6 months, or physiologically post-menopausal (i.e. spontaneous amenorrhea) for at least 1 year, and who will adhere to contraceptive requirements from at least 10 days before Period I check-in, during the study and up until 1 month after the end of the study. * Availability of the subject for the entire study period and willingness of the subject to adhere to protocol requirements, as evidenced by a signed ICF.
Exclusion criteria
* Known history of hypersensitivity to norethindrone and estradiol combinations and/or norethindrone, and/or estradiol. * Known history or presence of cardiac, pulmonary, gastrointestinal, endocrine, musculoskeletal, neurological, or hematological diseases, malignancies, or migraines, unless deemed not clinically significant by the Principal Investigator or Sub-Investigator. * Known history of liver, kidney, and/or gallbladder dysfunction/disease, chronic diarrhea, or inflammatory bowel diseases. * Known history or presence of cerebrovascular diseases or venous thromboembolic events, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis. * Any history of stroke. * Presence of any significant physical or organ abnormality. * History of osteoporosis. * History or presence of fibrocystic breast disease. * History or presence of breast, endometrial, cervical, and/or uterine carcinoma. * Any illness during the 4 weeks before this study, unless deemed not clinically significant by the Principal Investigator or Sub-Investigator. * Any history or evidence of psychiatric or psychological disease, unless deemed not clinically significant by the Principal Investigator or the Sub-Investigator. * Any history or abnormal vaginal bleeding, unless deemed not clinically significant by the Principal Investigator or the Sub-Investigator. * Any history of asthma (after 12 years of age). * Evidence of pregnancy or lactation. * Any history of severe allergic reaction (including drugs, food, insect bites, environmental allergens). * Known history or presence of food allergies, or any condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs. * Any history or drug abuse. * Any recent history of alcohol abuse (less than 1 year). * Use of any prescription medication within 30 days preceding this study. * Use of hormone replacement therapy within 30 days before drug administration. * Use of over-the-counter (OTC) medication or any herbal supplement within the 7 days preceding this study. * Use of hormonal contraceptives, oral, transdermal, implant within 30 days before drug administration or a depot injection or progestogen drug within 1 year before the drug administration. * Depot injection of any drug within 6 months. * Blood draws within 56 days preceding this study, during the conduct of any clinical study at another facility, or within the lockout period specified by previous study. * Blood donations within 56 days preceding this study. * Participation as a plasma donor in a plasmapheresis program within 7 days preceding this study. * Participation in a clinical trial with an investigational drug within 30 days preceding this study. * Intolerance to venipuncture.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Norethindrone (Maximum Observed Concentration of Drug Substance in Plasma) | Blood samples collected over a 36 hour period. | Bioequivalence based on Norethindrone Cmax. |
| AUC0-t of Norethindrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | Blood samples collected over a 36 hour period. | Bioequivalence based on Norethindrone AUC0-t. |
| AUC0-inf of Norethindrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | Blood samples collected over a 36 hour period. | Bioequivalence based on Norethindrone AUC0-inf. |
| Cmax of Corrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | Blood samples collected over a 72 hour period. | Bioequivalence based on Corrected Total Estrone Cmax. |
| AUC0-t of Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | Blood samples collected over a 72 hour period. | Bioequivalence based on Corrected Total Estrone AUC0-t. |
| AUC0-inf of Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | Blood samples collected over a 72 hour period. | Bioequivalence based on Corrected Total Estrone AUC0-inf. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Uncorrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | Blood samples collected over a 72 hour period. | Informational comparison of Cmax values for Uncorrected Unconjugated Estrone. |
| AUC0-t of Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | Blood samples collected over a 72 hour period. | Informational comparison of AUC0-t values for Uncorrected Unconjugated Estrone. |
| AUC0-inf of Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | Blood samples collected over a 72 hour period. | Informational comparison of AUC0-inf values for Uncorrected Unconjugated Estrone. |
| Cmax of Corrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma) | Blood samples collected over a 72 hour period. | Informational comparison of Cmax values for Corrected Unconjugated Estradiol. |
| Cmax of Uncorrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | Blood samples collected over a 72 hour period. | Informational comparison of Cmax values for Uncorrected Total Estrone. |
| AUC0-inf of Corrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity) | Blood samples collected over a 72 hour period. | Informational comparison of AUC0-inf values for Corrected Unconjugated Estradiol. |
| Cmax of Corrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | Blood samples collected over a 72 hour period. | Informational comparison of Cmax values for Corrected Unconjugated Estrone. |
| AUC0-t of Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | Blood samples collected over a 72 hour period. | Informational comparison of AUC0-t values for Corrected Unconjugated Estrone. |
| AUC0-inf of Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | Blood samples collected over a 72 hour period. | Informational comparison of AUC0-inf values for Corrected Unconjugated Estrone. |
| AUC0-t of Corrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | Blood samples collected over a 72 hour period. | Informational comparison of AUC0-t values for Corrected Unconjugated Estradiol. |
| AUC0-t of Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | Blood samples collected over a 72 hour period. | Informational comparison of AUC0-t values for Uncorrected Total Estrone. |
| AUC0-inf of Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | Blood samples collected over a 72 hour period. | Informational comparison of AUC0-inf values for Uncorrected Total Estrone. |
| Cmax of Uncorrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma) | Blood samples collected over a 72 hour period. | Informational comparison of Cmax values for Uncorrected Unconjugated Estradiol. |
| AUC0-t of Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | Blood samples collected over a 72 hour period. | Informational comparison of AUC0-t values for Uncorrected Unconjugated Estradiol. |
| AUC0-inf of Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity) | Blood samples collected over a 72 hour period. | Informational comparison of AUC0-inf values for Uncorrected Unconjugated Estradiol. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Estradiol/Norethindrone Acetate (Test) First 1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in first period followed by 1 mg/0.5 mg Activella® Tablets reference product dosed in the second period. | 20 |
| Activella® (Reference) First 1 mg/0.5 mg Activella® Tablets reference product dosed in first period followed by 1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in the second period. | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Activella® (Reference) First | Total | Estradiol/Norethindrone Acetate (Test) First |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 40 Participants | 20 Participants |
| Race/Ethnicity, Customized American Indian | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 1 participants | 3 participants | 2 participants |
| Race/Ethnicity, Customized Black | 2 participants | 4 participants | 2 participants |
| Race/Ethnicity, Customized Caucasian | 15 participants | 28 participants | 13 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 4 participants | 3 participants |
| Region of Enrollment Canada | 20 participants | 40 participants | 20 participants |
| Sex: Female, Male Female | 20 Participants | 40 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 40 | 2 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 |
Outcome results
Primary
AUC0-inf of Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
Bioequivalence based on Corrected Total Estrone AUC0-inf.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | AUC0-inf of Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 380131.12 pg*h/mL | Standard Deviation 163543.17 |
| Activella® (Reference) | AUC0-inf of Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 424801.99 pg*h/mL | Standard Deviation 216597.41 |
90% CI: [91.18, 99.51]
Primary
AUC0-inf of Norethindrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
Bioequivalence based on Norethindrone AUC0-inf.
Time frame: Blood samples collected over a 36 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | AUC0-inf of Norethindrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 49.55 ng*h/mL | Standard Deviation 23.08 |
| Activella® (Reference) | AUC0-inf of Norethindrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 50.68 ng*h/mL | Standard Deviation 22.78 |
90% CI: [94.05, 101.3]
Primary
AUC0-t of Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Bioequivalence based on Corrected Total Estrone AUC0-t.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | AUC0-t of Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 384547.68 pg*h/mL | Standard Deviation 185543.06 |
| Activella® (Reference) | AUC0-t of Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 407028.98 pg*h/mL | Standard Deviation 191192.18 |
90% CI: [91.21, 99.39]
Primary
AUC0-t of Norethindrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Bioequivalence based on Norethindrone AUC0-t.
Time frame: Blood samples collected over a 36 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | AUC0-t of Norethindrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 45.03 ng*h/mL | Standard Deviation 21.76 |
| Activella® (Reference) | AUC0-t of Norethindrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 46.13 ng*h/mL | Standard Deviation 21.62 |
90% CI: [93.91, 101.02]
Primary
Cmax of Corrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma)
Bioequivalence based on Corrected Total Estrone Cmax.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | Cmax of Corrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | 27076.08 pg/mL | Standard Deviation 11600.13 |
| Activella® (Reference) | Cmax of Corrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | 27240.03 pg/mL | Standard Deviation 11610.7 |
90% CI: [92.21, 107.06]
Primary
Cmax of Norethindrone (Maximum Observed Concentration of Drug Substance in Plasma)
Bioequivalence based on Norethindrone Cmax.
Time frame: Blood samples collected over a 36 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | Cmax of Norethindrone (Maximum Observed Concentration of Drug Substance in Plasma) | 6.54 ng/mL | Standard Deviation 3.62 |
| Activella® (Reference) | Cmax of Norethindrone (Maximum Observed Concentration of Drug Substance in Plasma) | 6.06 ng/mL | Standard Deviation 2.95 |
90% CI: [94.22, 116.25]
Secondary
AUC0-inf of Corrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity)
Informational comparison of AUC0-inf values for Corrected Unconjugated Estradiol.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | AUC0-inf of Corrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity) | 1823.43 pg*h/mL | Standard Deviation 551.11 |
| Activella® (Reference) | AUC0-inf of Corrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity) | 1871.56 pg*h/mL | Standard Deviation 730.51 |
90% CI: [94.17, 104.11]
Secondary
AUC0-inf of Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
Informational comparison of AUC0-inf values for Corrected Unconjugated Estrone.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | AUC0-inf of Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 11293.21 pg*h/mL | Standard Deviation 3899.12 |
| Activella® (Reference) | AUC0-inf of Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 11747.97 pg*h/mL | Standard Deviation 5289.05 |
90% CI: [94.11, 102.02]
Secondary
AUC0-inf of Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
Informational comparison of AUC0-inf values for Uncorrected Total Estrone.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | AUC0-inf of Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 398139.63 pg*h/mL | Standard Deviation 173723.79 |
| Activella® (Reference) | AUC0-inf of Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 425739.45 pg*h/mL | Standard Deviation 198546.75 |
90% CI: [91.17, 99.47]
Secondary
AUC0-inf of Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity)
Informational comparison of AUC0-inf values for Uncorrected Unconjugated Estradiol.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | AUC0-inf of Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity) | 2301.59 pg*h/mL | Standard Deviation 642.09 |
| Activella® (Reference) | AUC0-inf of Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity) | 2274.04 pg*h/mL | Standard Deviation 784.48 |
90% CI: [94.42, 105.3]
Secondary
AUC0-inf of Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
Informational comparison of AUC0-inf values for Uncorrected Unconjugated Estrone.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | AUC0-inf of Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 13592.44 pg*h/mL | Standard Deviation 3686.14 |
| Activella® (Reference) | AUC0-inf of Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 14155.46 pg*h/mL | Standard Deviation 5300.06 |
90% CI: [94.54, 101.6]
Secondary
AUC0-t of Corrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Informational comparison of AUC0-t values for Corrected Unconjugated Estradiol.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | AUC0-t of Corrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 1723.44 pg*h/mL | Standard Deviation 540.76 |
| Activella® (Reference) | AUC0-t of Corrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 1793.04 pg*h/mL | Standard Deviation 689.12 |
90% CI: [93.66, 102.46]
Secondary
AUC0-t of Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Informational comparison of AUC0-t values for Corrected Unconjugated Estrone.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | AUC0-t of Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 10952.25 pg*h/mL | Standard Deviation 3887.84 |
| Activella® (Reference) | AUC0-t of Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 11369.60 pg*h/mL | Standard Deviation 5058.92 |
90% CI: [94.03, 101.56]
Secondary
AUC0-t of Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Informational comparison of AUC0-t values for Uncorrected Total Estrone.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | AUC0-t of Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 397537.88 pg*h/mL | Standard Deviation 193337.67 |
| Activella® (Reference) | AUC0-t of Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 420763.02 pg*h/mL | Standard Deviation 198975.61 |
90% CI: [91.18, 99.38]
Secondary
AUC0-t of Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Informational comparison of AUC0-t values for Uncorrected Unconjugated Estradiol.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | AUC0-t of Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 2016.26 pg*h/mL | Standard Deviation 596.4 |
| Activella® (Reference) | AUC0-t of Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 2086.39 pg*h/mL | Standard Deviation 746.24 |
90% CI: [93.92, 101.78]
Secondary
AUC0-t of Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Informational comparison of AUC0-t values for Uncorrected Unconjugated Estrone.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | AUC0-t of Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 12444.22 pg*h/mL | Standard Deviation 4018.39 |
| Activella® (Reference) | AUC0-t of Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 12977.00 pg*h/mL | Standard Deviation 5291.36 |
90% CI: [94.55, 101.21]
Secondary
Cmax of Corrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma)
Informational comparison of Cmax values for Corrected Unconjugated Estradiol.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | Cmax of Corrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma) | 55.18 pg/mL | Standard Deviation 19.31 |
| Activella® (Reference) | Cmax of Corrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma) | 56.24 pg/mL | Standard Deviation 19.26 |
90% CI: [93.22, 102.74]
Secondary
Cmax of Corrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma)
Informational comparison of Cmax values for Corrected Unconjugated Estrone.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | Cmax of Corrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | 492.81 pg/mL | Standard Deviation 166.57 |
| Activella® (Reference) | Cmax of Corrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | 509.81 pg/mL | Standard Deviation 217.8 |
90% CI: [94.39, 104.1]
Secondary
Cmax of Uncorrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma)
Informational comparison of Cmax values for Uncorrected Total Estrone.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | Cmax of Uncorrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | 27256.41 pg/mL | Standard Deviation 11652.78 |
| Activella® (Reference) | Cmax of Uncorrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | 27430.77 pg/mL | Standard Deviation 11674.97 |
90% CI: [92.21, 107]
Secondary
Cmax of Uncorrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma)
Informational comparison of Cmax values for Uncorrected Unconjugated Estradiol.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | Cmax of Uncorrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma) | 59.24 pg/mL | Standard Deviation 19.1 |
| Activella® (Reference) | Cmax of Uncorrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma) | 60.33 pg/mL | Standard Deviation 19.04 |
90% CI: [93.44, 102.61]
Secondary
Cmax of Uncorrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma)
Informational comparison of Cmax values for Uncorrected Unconjugated Estrone.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | Cmax of Uncorrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | 513.56 pg/mL | Standard Deviation 165.85 |
| Activella® (Reference) | Cmax of Uncorrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | 529.23 pg/mL | Standard Deviation 217.12 |
90% CI: [94.71, 103.87]