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Trial record 41 of 2077 for:    ESTRADIOL

Estradiol/Norethindrone Acetate Tablets, 1/0.5 mg Under Fed Conditions

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01181726
Recruitment Status : Completed
First Posted : August 13, 2010
Results First Posted : October 7, 2010
Last Update Posted : December 8, 2010
Sponsor:
Information provided by:
Teva Pharmaceuticals USA

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label)
Condition Healthy
Interventions Drug: Estradiol/Norethindrone acetate
Drug: Activella®
Enrollment 40
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Estradiol/Norethindrone Acetate (Test) First Activella® (Reference) First
Hide Arm/Group Description 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. 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.
Period Title: First Intervention
Started 20 20
Completed 19 20
Not Completed 1 0
Reason Not Completed
Adverse Event             1             0
Period Title: Washout of 28 Days
Started 19 20
Completed 19 20
Not Completed 0 0
Period Title: Second Intervention
Started 19 20
Completed 19 20
Not Completed 0 0
Arm/Group Title Estradiol/Norethindrone Acetate (Test) First Activella® (Reference) First Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 20 20 40
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 20 participants 40 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
20
 100.0%
20
 100.0%
40
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 20 participants 40 participants
Female
20
 100.0%
20
 100.0%
40
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 20 participants 20 participants 40 participants
Caucasian 13 15 28
Hispanic 3 1 4
Black 2 2 4
Asian 2 1 3
American Indian 0 1 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Canada Number Analyzed 20 participants 20 participants 40 participants
20 20 40
1.Primary Outcome
Title Cmax of Norethindrone (Maximum Observed Concentration of Drug Substance in Plasma)
Hide Description Bioequivalence based on Norethindrone Cmax.
Time Frame Blood samples collected over a 36 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: ng/mL
6.54  (3.62) 6.06  (2.95)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 104.66
Confidence Interval (2-Sided) 90%
94.22 to 116.25
Estimation Comments Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference (R) and test (T) product fall within the interval of 80-125%.
2.Primary Outcome
Title AUC0-t of Norethindrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Hide Description Bioequivalence based on Norethindrone AUC0-t.
Time Frame Blood samples collected over a 36 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
45.03  (21.76) 46.13  (21.62)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 97.4
Confidence Interval (2-Sided) 90%
93.91 to 101.02
Estimation Comments Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference (R) and test (T) product fall within the interval of 80-125%.
3.Primary Outcome
Title AUC0-inf of Norethindrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
Hide Description Bioequivalence based on Norethindrone AUC0-inf.
Time Frame Blood samples collected over a 36 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
49.55  (23.08) 50.68  (22.78)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 97.60
Confidence Interval (2-Sided) 90%
94.05 to 101.30
Estimation Comments Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference (R) and test (T) product fall within the interval of 80-125%.
4.Primary Outcome
Title Cmax of Corrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma)
Hide Description Bioequivalence based on Corrected Total Estrone Cmax.
Time Frame Blood samples collected over a 72 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: pg/mL
27076.08  (11600.13) 27240.03  (11610.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 99.35
Confidence Interval (2-Sided) 90%
92.21 to 107.06
Estimation Comments Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference (R) and test (T) product fall within the interval of 80-125%.
5.Primary Outcome
Title AUC0-t of Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Hide Description Bioequivalence based on Corrected Total Estrone AUC0-t.
Time Frame Blood samples collected over a 72 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: pg*h/mL
384547.68  (185543.06) 407028.98  (191192.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 95.21
Confidence Interval (2-Sided) 90%
91.21 to 99.39
Estimation Comments Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference (R) and test (T) product fall within the interval of 80-125%.
6.Primary Outcome
Title AUC0-inf of Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
Hide Description Bioequivalence based on Corrected Total Estrone AUC0-inf.
Time Frame Blood samples collected over a 72 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: pg*h/mL
380131.12  (163543.17) 424801.99  (216597.41)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 95.25
Confidence Interval (2-Sided) 90%
91.18 to 99.51
Estimation Comments Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference (R) and test (T) product fall within the interval of 80-125%.
7.Secondary Outcome
Title Cmax of Uncorrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma)
Hide Description Informational comparison of Cmax values for Uncorrected Total Estrone.
Time Frame Blood samples collected over a 72 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: pg/mL
27256.41  (11652.78) 27430.77  (11674.97)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 99.33
Confidence Interval (2-Sided) 90%
92.21 to 107.00
Estimation Comments This analysis was for informational purposes only and was not used to establish bioequivalence.
8.Secondary Outcome
Title AUC0-t of Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Hide Description Informational comparison of AUC0-t values for Uncorrected Total Estrone.
Time Frame Blood samples collected over a 72 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: pg*h/mL
397537.88  (193337.67) 420763.02  (198975.61)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 95.19
Confidence Interval (2-Sided) 90%
91.18 to 99.38
Estimation Comments This analysis was for informational purposes only and was not used to establish bioequivalence.
9.Secondary Outcome
Title AUC0-inf of Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
Hide Description Informational comparison of AUC0-inf values for Uncorrected Total Estrone.
Time Frame Blood samples collected over a 72 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: pg*h/mL
398139.63  (173723.79) 425739.45  (198546.75)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 95.23
Confidence Interval (2-Sided) 90%
91.17 to 99.47
Estimation Comments This analysis was for informational purposes only and was not used to establish bioequivalence.
10.Secondary Outcome
Title Cmax of Uncorrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma)
Hide Description Informational comparison of Cmax values for Uncorrected Unconjugated Estradiol.
Time Frame Blood samples collected over a 72 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: pg/mL
59.24  (19.10) 60.33  (19.04)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 97.92
Confidence Interval (2-Sided) 90%
93.44 to 102.61
Estimation Comments This analysis was for informational purposes only and was not used to establish bioequivalence.
11.Secondary Outcome
Title AUC0-t of Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Hide Description Informational comparison of AUC0-t values for Uncorrected Unconjugated Estradiol.
Time Frame Blood samples collected over a 72 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: pg*h/mL
2016.26  (596.40) 2086.39  (746.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 97.77
Confidence Interval (2-Sided) 90%
93.92 to 101.78
Estimation Comments This analysis was for informational purposes only and was not used to establish bioequivalence.
12.Secondary Outcome
Title AUC0-inf of Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity)
Hide Description Informational comparison of AUC0-inf values for Uncorrected Unconjugated Estradiol.
Time Frame Blood samples collected over a 72 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: pg*h/mL
2301.59  (642.09) 2274.04  (784.48)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 99.71
Confidence Interval (2-Sided) 90%
94.42 to 105.30
Estimation Comments This analysis was for informational purposes only and was not used to establish bioequivalence.
13.Secondary Outcome
Title Cmax of Uncorrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma)
Hide Description Informational comparison of Cmax values for Uncorrected Unconjugated Estrone.
Time Frame Blood samples collected over a 72 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: pg/mL
513.56  (165.85) 529.23  (217.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 99.19
Confidence Interval (2-Sided) 90%
94.71 to 103.87
Estimation Comments This analysis was for informational purposes only and was not used to establish bioequivalence.
14.Secondary Outcome
Title AUC0-t of Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Hide Description Informational comparison of AUC0-t values for Uncorrected Unconjugated Estrone.
Time Frame Blood samples collected over a 72 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: pg*h/mL
12444.22  (4018.39) 12977.00  (5291.36)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 97.83
Confidence Interval (2-Sided) 90%
94.55 to 101.21
Estimation Comments This analysis was for informational purposes only and was not used to establish bioequivalence.
15.Secondary Outcome
Title AUC0-inf of Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
Hide Description Informational comparison of AUC0-inf values for Uncorrected Unconjugated Estrone.
Time Frame Blood samples collected over a 72 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: pg*h/mL
13592.44  (3686.14) 14155.46  (5300.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 98.01
Confidence Interval (2-Sided) 90%
94.54 to 101.60
Estimation Comments This analysis was for informational purposes only and was not used to establish bioequivalence.
16.Secondary Outcome
Title Cmax of Corrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma)
Hide Description Informational comparison of Cmax values for Corrected Unconjugated Estradiol.
Time Frame Blood samples collected over a 72 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: pg/mL
55.18  (19.31) 56.24  (19.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 97.87
Confidence Interval (2-Sided) 90%
93.22 to 102.74
Estimation Comments This analysis was for informational purposes only and was not used to establish bioequivalence.
17.Secondary Outcome
Title AUC0-t of Corrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Hide Description Informational comparison of AUC0-t values for Corrected Unconjugated Estradiol.
Time Frame Blood samples collected over a 72 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: pg*h/mL
1723.44  (540.76) 1793.04  (689.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 97.96
Confidence Interval (2-Sided) 90%
93.66 to 102.46
Estimation Comments This analysis was for informational purposes only and was not used to establish bioequivalence.
18.Secondary Outcome
Title AUC0-inf of Corrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity)
Hide Description Informational comparison of AUC0-inf values for Corrected Unconjugated Estradiol.
Time Frame Blood samples collected over a 72 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: pg*h/mL
1823.43  (551.11) 1871.56  (730.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 99.01
Confidence Interval (2-Sided) 90%
94.17 to 104.11
Estimation Comments This analysis was for informational purposes only and was not used to establish bioequivalence.
19.Secondary Outcome
Title Cmax of Corrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma)
Hide Description Informational comparison of Cmax values for Corrected Unconjugated Estrone.
Time Frame Blood samples collected over a 72 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: pg/mL
492.81  (166.57) 509.81  (217.80)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 99.13
Confidence Interval (2-Sided) 90%
94.39 to 104.10
Estimation Comments This analysis was for informational purposes only and was not used to establish bioequivalence.
20.Secondary Outcome
Title AUC0-t of Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Hide Description Informational comparison of AUC0-t values for Corrected Unconjugated Estrone.
Time Frame Blood samples collected over a 72 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: pg*h/mL
10952.25  (3887.84) 11369.60  (5058.92)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 97.72
Confidence Interval (2-Sided) 90%
94.03 to 101.56
Estimation Comments This analysis was for informational purposes only and was not used to establish bioequivalence.
21.Secondary Outcome
Title AUC0-inf of Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
Hide Description Informational comparison of AUC0-inf values for Corrected Unconjugated Estrone.
Time Frame Blood samples collected over a 72 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description:
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: pg*h/mL
11293.21  (3899.12) 11747.97  (5289.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol/Norethindrone Acetate (Test), Activella® (Reference)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Method of Estimation Estimation Parameter Ratio of the T/R geometric mean x 100
Estimated Value 97.99
Confidence Interval (2-Sided) 90%
94.11 to 102.02
Estimation Comments This analysis was for informational purposes only and was not used to establish bioequivalence.
Time Frame Adverse event data was collected over the course of the study, which was approximately 6 weeks in duration.
Adverse Event Reporting Description Volunteers were monitored throughout the study for any adverse experiences. AEs were collected through both solicited and unsolicited methods. The volunteers were encouraged to report signs, symptoms, and any changes in health to the clinic staff.
 
Arm/Group Title Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Hide Arm/Group Description 1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period. 1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
All-Cause Mortality
Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/40 (0.00%)      0/40 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Estradiol/Norethindrone Acetate (Test) Activella® (Reference)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/40 (2.50%)      2/40 (5.00%)    
General disorders     
Headache * 1  1/40 (2.50%)  1 2/40 (5.00%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (Unspecified)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Principal Investigator is not permitted to discuss or publish trial results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Associate Director, Biopharmaceutics
Organization: TEVA Pharmaceuticals, USA
Phone: 1-866-384-5525
EMail: clinicaltrialqueries@tevausa.com
Layout table for additonal information
ClinicalTrials.gov Identifier: NCT01181726     History of Changes
Other Study ID Numbers: 3252
First Submitted: August 11, 2010
First Posted: August 13, 2010
Results First Submitted: September 15, 2010
Results First Posted: October 7, 2010
Last Update Posted: December 8, 2010