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Drospirenone/Ethinyl Estradiol (3 mg/0.02 mg) Tablets Under Non-Fasting Conditions

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ClinicalTrials.gov Identifier: NCT01182207
Recruitment Status : Completed
First Posted : August 16, 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: Drospirenone/Ethinyl Estradiol (Gianvi®)
Drug: YAZ®
Enrollment 33
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Drospirenone/Ethinyl Estradiol (Test) First YAZ® (Reference) First
Hide Arm/Group Description 3 mg/0.02 mg Drospirenone/Ethinyl Estradiol Tablets test product dosed in first period followed by 3 mg/0.02 mg YAZ® Tablets reference product dosed in the second period. 3 mg/0.02 mg YAZ® Tablets reference product dosed in first period followed by 3 mg/0.02 mg Drospirenone/Ethinyl Estradiol test product dosed in the second period.
Period Title: First Intervention
Started 18 15
Completed 18 14
Not Completed 0 1
Reason Not Completed
Positive Hepatitis Results             0             1
Period Title: Washout of 28 Days
Started 18 14
Completed 18 14
Not Completed 0 0
Period Title: Second Intervention
Started 18 14
Completed 17 14
Not Completed 1 0
Reason Not Completed
Emeses within 1 hour of dosing             1             0
Arm/Group Title Drospirenone/Ethinyl Estradiol (Test) First YAZ® (Reference) First Total
Hide Arm/Group Description 3 mg/0.02 mg Drospirenone/Ethinyl Estradiol Tablets test product dosed in first period followed by 3 mg/0.02 mg YAZ® Tablets reference product dosed in the second period. 3 mg/0.02 mg YAZ® Tablets reference product dosed in first period followed by 3 mg/0.02 mg Drospirenone/Ethinyl Estradiol test product dosed in the second period. Total of all reporting groups
Overall Number of Baseline Participants 18 15 33
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 15 participants 33 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
18
 100.0%
15
 100.0%
33
 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 18 participants 15 participants 33 participants
Female
18
 100.0%
15
 100.0%
33
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 18 participants 15 participants 33 participants
Caucasian 17 13 30
Hispanic 0 1 1
More than One 1 0 1
American Indian 0 1 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 18 participants 15 participants 33 participants
18 15 33
1.Primary Outcome
Title Cmax of Drospirenone(Maximum Observed Concentration of Drug Substance in Plasma)
Hide Description Bioequivalence based on Drospirenone Cmax.
Time Frame Blood samples collected over a 120 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Drospirenone/Ethinyl Estradiol (Test) YAZ® (Reference)
Hide Arm/Group Description:
3 mg/0.02 mg Drospirenone/Ethinyl Estradiol Tablets test product dosed in either period.
3 mg/0.02 mg YAZ® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 31 31
Mean (Standard Deviation)
Unit of Measure: ng/mL
52.77  (15.77) 53.65  (13.82)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Drospirenone/Ethinyl Estradiol (Test), YAZ® (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 96.74
Confidence Interval (2-Sided) 90%
86.82 to 107.79
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 Drospirenone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Hide Description Bioequivalence based on Drospirenone AUC0-t.
Time Frame Blood samples collected over a 120 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Drospirenone/Ethinyl Estradiol (Test) YAZ® (Reference)
Hide Arm/Group Description:
3 mg/0.02 mg Drospirenone/Ethinyl Estradiol Tablets test product dosed in either period.
3 mg/0.02 mg YAZ® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 31 31
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
889.67  (187.51) 867.10  (207.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Drospirenone/Ethinyl Estradiol (Test), YAZ® (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 103.16
Confidence Interval (2-Sided) 90%
101.10 to 105.27
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 Drospirenone(Area Under the Concentration-time Curve From Time Zero to Infinity)
Hide Description Bioequivalence based on Drospirenone AUC0-inf.
Time Frame Blood samples collected over a 120 hour period.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Drospirenone/Ethinyl Estradiol (Test) YAZ® (Reference)
Hide Arm/Group Description:
3 mg/0.02 mg Drospirenone/Ethinyl Estradiol Tablets test product dosed in either period.
3 mg/0.02 mg YAZ® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 31 31
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
951.18  (226.13) 930.38  (236.38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Drospirenone/Ethinyl Estradiol (Test), YAZ® (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 102.72
Confidence Interval (2-Sided) 90%
100.67 to 104.80
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 Ethinyl Estradiol(Maximum Observed Concentration of Drug Substance in Plasma)
Hide Description Bioequivalence based on Ethinyl Estradiol 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 Drospirenone/Ethinyl Estradiol (Test) YAZ® (Reference)
Hide Arm/Group Description:
3 mg/0.02 mg Drospirenone/Ethinyl Estradiol Tablets test product dosed in either period.
3 mg/0.02 mg YAZ® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 31 31
Mean (Standard Deviation)
Unit of Measure: pg/mL
87.95  (29.22) 91.23  (36.79)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Drospirenone/Ethinyl Estradiol (Test), YAZ® (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%
89.45 to 106.50
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 Ethinyl Estradiol(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Hide Description Bioequivalence based on Ethinyl Estradiol 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 Drospirenone/Ethinyl Estradiol (Test) YAZ® (Reference)
Hide Arm/Group Description:
3 mg/0.02 mg Drospirenone/Ethinyl Estradiol Tablets test product dosed in either period.
3 mg/0.02 mg YAZ® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 31 31
Mean (Standard Deviation)
Unit of Measure: pg*h/mL
1066.24  (372.97) 1079.54  (344.21)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Drospirenone/Ethinyl Estradiol (Test), YAZ® (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 98.88
Confidence Interval (2-Sided) 90%
95.62 to 102.25
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%.
6.Primary Outcome
Title AUC0-inf of Ethinyl Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity)
Hide Description Bioequivalence based on Ethinyl Estradiol 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 Drospirenone/Ethinyl Estradiol (Test) YAZ® (Reference)
Hide Arm/Group Description:
3 mg/0.02 mg Drospirenone/Ethinyl Estradiol Tablets test product dosed in either period.
3 mg/0.02 mg YAZ® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 31 31
Mean (Standard Deviation)
Unit of Measure: pg*h/mL
1155.69  (394.56) 1175.76  (358.58)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Drospirenone/Ethinyl Estradiol (Test), YAZ® (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 98.20
Confidence Interval (2-Sided) 90%
95.36 to 101.12
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%.
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 Drospirenone/Ethinyl Estradiol (Test) YAZ® (Reference)
Hide Arm/Group Description 3 mg/0.02 mg Drospirenone/Ethinyl Estradiol Tablets test product dosed in either period. 3 mg/0.02 mg YAZ® Tablets reference product dosed in either period.
All-Cause Mortality
Drospirenone/Ethinyl Estradiol (Test) YAZ® (Reference)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Drospirenone/Ethinyl Estradiol (Test) YAZ® (Reference)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/33 (0.00%)      0/33 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Drospirenone/Ethinyl Estradiol (Test) YAZ® (Reference)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   21/33 (63.64%)      11/33 (33.33%)    
General disorders     
Nausea * 1  6/33 (18.18%)  7 4/33 (12.12%)  4
Dysmenorrhoea * 1  4/33 (12.12%)  4 2/33 (6.06%)  2
Metrorrhagia * 1  2/33 (6.06%)  2 3/33 (9.09%)  3
Abdominal Pain * 1  3/33 (9.09%)  4 4/33 (12.12%)  4
Vomitting * 1  3/33 (9.09%)  6 2/33 (6.06%)  2
Pharynogolaryngeal Pain * 1  3/33 (9.09%)  3 0/33 (0.00%)  0
Headache * 1  8/33 (24.24%)  9 3/33 (9.09%)  3
Sinus Headache * 1  2/33 (6.06%)  2 0/33 (0.00%)  0
Menstrual Disorder * 1  1/33 (3.03%)  1 2/33 (6.06%)  2
Stomach Discomfort * 1  2/33 (6.06%)  2 0/33 (0.00%)  0
Dizziness * 1  2/33 (6.06%)  2 4/33 (12.12%)  5
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (9.0)
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: NCT01182207     History of Changes
Other Study ID Numbers: R06-0632
First Submitted: August 12, 2010
First Posted: August 16, 2010
Results First Submitted: September 15, 2010
Results First Posted: October 7, 2010
Last Update Posted: December 8, 2010