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

This study has been completed.
Sponsor:
Information provided by:
Teva Pharmaceuticals USA
ClinicalTrials.gov Identifier:
NCT01157182
First received: July 2, 2010
Last updated: November 22, 2010
Last verified: November 2010
Results First Received: September 15, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Bio-equivalence Study;   Intervention Model: Crossover Assignment;   Masking: Open Label
Condition: Healthy
Interventions: Drug: Estradiol/Norethindrone acetate
Drug: Activella®

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
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.
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.

Participant Flow for 3 periods

Period 1:   First Intervention
    Estradiol/Norethindrone Acetate (Test) First     Activella® (Reference) First  
STARTED     18     18  
COMPLETED     18     18  
NOT COMPLETED     0     0  

Period 2:   Washout of 28 Days
    Estradiol/Norethindrone Acetate (Test) First     Activella® (Reference) First  
STARTED     18     18  
COMPLETED     16     18  
NOT COMPLETED     2     0  
Adverse Event                 2                 0  

Period 3:   Second Intervention
    Estradiol/Norethindrone Acetate (Test) First     Activella® (Reference) First  
STARTED     16     18  
COMPLETED     16     18  
NOT COMPLETED     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.
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.
Total Total of all reporting groups

Baseline Measures
    Estradiol/Norethindrone Acetate (Test) First     Activella® (Reference) First     Total  
Number of Participants  
[units: participants]
  18     18     36  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     17     18     35  
>=65 years     1     0     1  
Gender  
[units: participants]
     
Female     18     18     36  
Male     0     0     0  
Race/Ethnicity, Customized  
[units: participants]
     
Caucasian     12     14     26  
Hispanic     0     3     3  
Black     3     0     3  
Asian     3     0     3  
American Indian     0     1     1  
Region of Enrollment  
[units: participants]
     
Canada     18     18     36  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Cmax for Norethindrone(Maximum Observed Concentration of Drug Substance in Plasma)   [ Time Frame: Blood samples collected over a 36 hour period. ]

2.  Primary:   AUC0-t for Norethindrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)   [ Time Frame: Blood samples collected over a 36 hour period. ]

3.  Primary:   AUC0-inf for Norethindrone(Area Under the Concentration-time Curve From Time Zero to Infinity)   [ Time Frame: Blood samples collected over a 36 hour period. ]

4.  Primary:   Cmax for Corrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma)   [ Time Frame: Blood samples collected over a 72 hour period. ]
  Hide Outcome Measure 4

Measure Type Primary
Measure Title Cmax for Corrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma)
Measure Description Bioequivalence based on Corrected Total Estrone Cmax.
Time Frame Blood samples collected over a 72 hour period.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants that completed the study had their samples analyzed.

Reporting Groups
  Description
Estradiol/Norethindrone Acetate (Test) 1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
Activella® (Reference) 1/0.5 mg Activella® Tablets reference product dosed in either period.

Measured Values
    Estradiol/Norethindrone Acetate (Test)     Activella® (Reference)  
Number of Participants Analyzed  
[units: participants]
  34     34  
Cmax for Corrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma)  
[units: pg/mL]
Mean ± Standard Deviation
  43997.17  ± 10387.84     47015.47  ± 9894.22  


Statistical Analysis 1 for Cmax for Corrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma)
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Ratio of the T/R geometric mean x 100 [3] 92.51
90% Confidence Interval ( 88.64 to 96.55 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  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).
[3] Other relevant estimation information:
  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:   AUC0-t for Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)   [ Time Frame: Blood samples collected over a 72 hour period. ]

6.  Primary:   AUC0-inf for Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)   [ Time Frame: Blood samples collected over a 72 hour period. ]

7.  Secondary:   Cmax for Uncorrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma)   [ Time Frame: Blood samples collected over a 72 hour period. ]

8.  Secondary:   AUC0-t for Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)   [ Time Frame: Blood samples collected over a 72 hour period. ]

9.  Secondary:   AUC0-inf for Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)   [ Time Frame: Blood samples collected over a 72 hour period. ]

10.  Secondary:   Cmax for Uncorrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma)   [ Time Frame: Blood samples collected over a 72 hour period. ]

11.  Secondary:   AUC0-t for Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)   [ Time Frame: Blood samples collected over a 72 hour period. ]

12.  Secondary:   AUC0-inf for Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity)   [ Time Frame: Blood samples collected over a 72 hour period. ]

13.  Secondary:   Cmax for Uncorrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma)   [ Time Frame: Blood samples collected over a 72 hour period. ]

14.  Secondary:   AUC0-t for Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)   [ Time Frame: Blood samples collected over a 72 hour period. ]

15.  Secondary:   AUC0-inf for Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)   [ Time Frame: Blood samples collected over a 72 hour period. ]

16.  Secondary:   Cmax for Corrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma)   [ Time Frame: Blood samples collected over a 72 hour period. ]

17.  Secondary:   AUC0-t for Corrected Unconjugated Estradiol.(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)   [ Time Frame: Blood samples collected over a 72 hour period. ]

18.  Secondary:   AUC0-inf for Corrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity)   [ Time Frame: Blood samples collected over a 72 hour period. ]

19.  Secondary:   Cmax for Corrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma)   [ Time Frame: Blood samples collected over a 72 hour period. ]

20.  Secondary:   AUC0-t for Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)   [ Time Frame: Blood samples collected over a 72 hour period. ]

21.  Secondary:   AUC0-inf for Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)   [ Time Frame: Blood samples collected over a 72 hour period. ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Associate Director, Biopharmaceutics
Organization: TEVA Pharmaceuticals, USA
phone: 1-866-384-5525
e-mail: clinicaltrialqueries@tevausa.com


No publications provided


Responsible Party: Associate Director, Biopharmaceutics, TEVA Pharmaceuticals, USA
ClinicalTrials.gov Identifier: NCT01157182     History of Changes
Other Study ID Numbers: 3251
Study First Received: July 2, 2010
Results First Received: September 15, 2010
Last Updated: November 22, 2010
Health Authority: United States: Institutional Review Board