Healthy
Conditions
Keywords
Healthy, Bioequivalence, Post-Menopausal
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 fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA Bioequivalence Statistical Methods
Interventions
1/0.5 mg Tablets
DRUGActivella®
1/0.5 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 \< 90 pmol/L and follicle-stimulating hormone (FSH) of \> 40 IU/L. * Body Mass Index greater than or equal to 19.0 and less than or equal to 32.0. * Normal findings in the physical examination, 12-lead electrocardiogram (ECG) and vital signs. * Hemoglobin \> 115 g/L * Normal Pap smear within 6 months. * 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 of the acceptable range as defined by BCR, unless the Principal Investigator or Sub-investigator decides that they are not clinically significant. * 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 to 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 evidence 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 NCS by the Principal Investigator or Sub-investigator. * Known history of liver, kidney, and/or gallbladder dysfunction/disease, chronic diarrhea or inflammatory bowel disease. * 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 the study, unless deemed NCS by the Principal Investigator or Sub-investigator. * Any history or evidence of psychiatric or psychological disease, unless deemed NCS by the Principal Investigator or Sub-investigator. * Any history of abnormal vaginal bleeding, unless deemed NCS by the Principal Investigator or 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 of 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 medication or any herbal supplement within the 7 days preceding this study (except for spermicidal/barrier contraceptive products). * Use of hormonal contraceptives within the 30 days before drug administration or a depot injection of progestogen drug within 1 year before drug administration. * Depot injection of any drug (other than progestogen) within 6 months. * Blood draws within 56 days preceding this study, during the conduct of any clinical study at a facility other than BCR, or within the lockout period specified by a previous study conducted at BCR. * 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 for Norethindrone(Maximum Observed Concentration of Drug Substance in Plasma) | Blood samples collected over a 36 hour period. | Bioequivalence based on Norethindrone Cmax. |
| AUC0-t for 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 for 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 for 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 for 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 for 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 for 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 for 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 for 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 for 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 for 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 for 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 for 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 for 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 for 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 for 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 for 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 for 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 for 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 for 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 for 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 1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in first period followed by 1/0.5 mg Activella® Tablets reference product dosed in the second period. | 18 |
| Activella® (Reference) First 1/0.5 mg Activella® Tablets reference product dosed in first period followed by 1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in the second period. | 18 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout of 28 Days | Adverse Event | 2 | 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 | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 35 Participants | 17 Participants |
| Race/Ethnicity, Customized American Indian | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 3 participants | 3 participants |
| Race/Ethnicity, Customized Black | 0 participants | 3 participants | 3 participants |
| Race/Ethnicity, Customized Caucasian | 14 participants | 26 participants | 12 participants |
| Race/Ethnicity, Customized Hispanic | 3 participants | 3 participants | 0 participants |
| Region of Enrollment Canada | 18 participants | 36 participants | 18 participants |
| Sex: Female, Male Female | 18 Participants | 36 Participants | 18 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 | 3 / 36 | 0 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 |
Outcome results
Primary
AUC0-inf for 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 for Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 375439.71 pg*h/mL | Standard Deviation 164404.58 |
| Activella® (Reference) | AUC0-inf for Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 384535.16 pg*h/mL | Standard Deviation 153333.46 |
90% CI: [92.62, 98.91]
Primary
AUC0-inf for 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 for Norethindrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 39.94 ng*h/mL | Standard Deviation 20.14 |
| Activella® (Reference) | AUC0-inf for Norethindrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 40.40 ng*h/mL | Standard Deviation 18.9 |
90% CI: [95.33, 102.26]
Primary
AUC0-t for 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 for Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 365242.88 pg*h/mL | Standard Deviation 155344.76 |
| Activella® (Reference) | AUC0-t for Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 374730.12 pg*h/mL | Standard Deviation 145770.97 |
90% CI: [92.6, 98.81]
Primary
AUC0-t for 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 for Norethindrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 36.59 ng*h/mL | Standard Deviation 19.54 |
| Activella® (Reference) | AUC0-t for Norethindrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 37.05 ng*h/mL | Standard Deviation 18.07 |
90% CI: [95.15, 101.76]
Primary
Cmax for 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 for Corrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | 43997.17 pg/mL | Standard Deviation 10387.84 |
| Activella® (Reference) | Cmax for Corrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | 47015.47 pg/mL | Standard Deviation 9894.22 |
90% CI: [88.64, 96.55]
Primary
Cmax for 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 for Norethindrone(Maximum Observed Concentration of Drug Substance in Plasma) | 10.08 ng/mL | Standard Deviation 3.32 |
| Activella® (Reference) | Cmax for Norethindrone(Maximum Observed Concentration of Drug Substance in Plasma) | 9.90 ng/mL | Standard Deviation 3.68 |
90% CI: [97.63, 108.55]
Secondary
AUC0-inf for 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 for Corrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity) | 1359.50 pg*h/mL | Standard Deviation 664.41 |
| Activella® (Reference) | AUC0-inf for Corrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity) | 1410.51 pg*h/mL | Standard Deviation 695.23 |
90% CI: [88.1, 103.81]
Secondary
AUC0-inf for 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 for Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 10267.03 pg*h/mL | Standard Deviation 4156.1 |
| Activella® (Reference) | AUC0-inf for Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 10214.23 pg*h/mL | Standard Deviation 4497.68 |
90% CI: [92.75, 100.93]
Secondary
AUC0-inf for 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 for Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 387085.29 pg*h/mL | Standard Deviation 172021.74 |
| Activella® (Reference) | AUC0-inf for Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 400726.94 pg*h/mL | Standard Deviation 160336.6 |
90% CI: [92.68, 98.88]
Secondary
AUC0-inf for 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 for Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity) | 1739.31 pg*h/mL | Standard Deviation 671.74 |
| Activella® (Reference) | AUC0-inf for Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity) | 1905.28 pg*h/mL | Standard Deviation 865.43 |
90% CI: [90.7, 104.76]
Secondary
AUC0-inf for 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 for Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 12387.14 pg*h/mL | Standard Deviation 4715.23 |
| Activella® (Reference) | AUC0-inf for Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity) | 12646.49 pg*h/mL | Standard Deviation 4673.97 |
90% CI: [93.62, 100.96]
Secondary
AUC0-t for 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 for Corrected Unconjugated Estradiol.(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 1267.50 pg*h/mL | Standard Deviation 574.02 |
| Activella® (Reference) | AUC0-t for Corrected Unconjugated Estradiol.(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 1323.70 pg*h/mL | Standard Deviation 615.33 |
90% CI: [88.37, 103.14]
Secondary
AUC0-t for 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 for Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 9409.59 pg*h/mL | Standard Deviation 4029.75 |
| Activella® (Reference) | AUC0-t for Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 9762.49 pg*h/mL | Standard Deviation 4170.35 |
90% CI: [92.14, 100.04]
Secondary
AUC0-t for 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 for Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 372088.37 pg*h/mL | Standard Deviation 159941.67 |
| Activella® (Reference) | AUC0-t for Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 385829.05 pg*h/mL | Standard Deviation 150207.71 |
90% CI: [92.68, 98.77]
Secondary
AUC0-t for 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 for Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 1575.01 pg*h/mL | Standard Deviation 670.36 |
| Activella® (Reference) | AUC0-t for Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 1656.16 pg*h/mL | Standard Deviation 680.55 |
90% CI: [89.04, 99.47]
Secondary
AUC0-t for 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 for Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 10870.03 pg*h/mL | Standard Deviation 4207.05 |
| Activella® (Reference) | AUC0-t for Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 11252.64 pg*h/mL | Standard Deviation 4220.2 |
90% CI: [92.73, 99.36]
Secondary
Cmax for 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 for Corrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma) | 47.80 pg/mL | Standard Deviation 19.05 |
| Activella® (Reference) | Cmax for Corrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma) | 51.59 pg/mL | Standard Deviation 18.77 |
90% CI: [84.46, 99.62]
Secondary
Cmax for 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 for Corrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | 455.16 pg/mL | Standard Deviation 153.38 |
| Activella® (Reference) | Cmax for Corrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | 481.46 pg/mL | Standard Deviation 163.19 |
90% CI: [89.56, 98.98]
Secondary
Cmax for 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 for Uncorrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | 43723.53 pg/mL | Standard Deviation 10562.4 |
| Activella® (Reference) | Cmax for Uncorrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | 47170.59 pg/mL | Standard Deviation 9913.52 |
90% CI: [88.65, 96.33]
Secondary
Cmax for 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 for Uncorrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma) | 52.09 pg/mL | Standard Deviation 19.78 |
| Activella® (Reference) | Cmax for Uncorrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma) | 56.26 pg/mL | Standard Deviation 18.96 |
90% CI: [84.62, 98.31]
Secondary
Cmax for 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 for Uncorrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | 475.44 pg/mL | Standard Deviation 155.4 |
| Activella® (Reference) | Cmax for Uncorrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma) | 502.24 pg/mL | Standard Deviation 163.45 |
90% CI: [89.78, 98.81]