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Losartan Potassium/Hydrochlorothiazide 100/25 mg Tablets in Healthy Subjects Under Non-Fasting Conditions

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ClinicalTrials.gov Identifier: NCT01149473
Recruitment Status : Completed
First Posted : June 23, 2010
Results First Posted : September 14, 2010
Last Update Posted : September 14, 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
Intervention Drug: Losartan potassium/Hydrochlorothiazide
Enrollment 80
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Losartan/HCTZ (Test) First Hyzaar® (Reference) First
Hide Arm/Group Description 100/25 mg Losartan potassium/Hydrochlorothiazide test product dosed in first period followed by 100/25 mg Hyzaar® Tablets reference product dosed in the second period. 100/25 mg Hyzaar® Tablets reference product dosed in first period followed by 100/25 mg Losartan potassium/Hydrochlorothiazide test product dosed in the second period.
Period Title: First Intervention
Started 40 40
Completed 39 39
Not Completed 1 1
Reason Not Completed
Adverse Event             1             1
Period Title: Washout of 7 Days
Started 39 39
Completed 38 38
Not Completed 1 1
Reason Not Completed
Withdrawal by Subject             1             1
Period Title: Second Intervention
Started 38 38
Completed 38 38
Not Completed 0 0
Arm/Group Title Losartan/HCTZ (Test) First Hyzaar® (Reference) First Total
Hide Arm/Group Description 100/25 mg Losartan potassium/Hydrochlorothiazide test product dosed in first period followed by 100/25 mg Hyzaar® Tablets reference product dosed in the second period. 100/25 mg Hyzaar® Tablets reference product dosed in first period followed by 100/25 mg Losartan potassium/Hydrochlorothiazide test product dosed in the second period. Total of all reporting groups
Overall Number of Baseline Participants 40 40 80
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 40 participants 80 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
40
 100.0%
39
  97.5%
79
  98.8%
>=65 years
0
   0.0%
1
   2.5%
1
   1.3%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 40 participants 80 participants
Female
7
  17.5%
7
  17.5%
14
  17.5%
Male
33
  82.5%
33
  82.5%
66
  82.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 40 participants 40 participants 80 participants
Asian 1 2 3
Black 3 2 5
Caucasian 35 36 71
Hispanic 1 0 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 40 participants 40 participants 80 participants
40 40 80
1.Primary Outcome
Title Cmax of Losartan(Maximum Observed Concentration of Drug Substance in Plasma)
Hide Description Bioequivalence based on Losartan Cmax.
Time Frame Blood samples collected over a 48 hour period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Losartan/HCTZ (Test) Hyzaar® (Reference)
Hide Arm/Group Description:
100/25 mg Losartan potassium/Hydrochlorothiazide test product dosed in either period.
100/25 mg Hyzaar® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 76 76
Mean (Standard Deviation)
Unit of Measure: ng/mL
458.29  (323.345) 409.324  (251.876)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Losartan/HCTZ (Test), Hyzaar® (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 109
Confidence Interval (2-Sided) 90%
98.1 to 120
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 Losartan(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Hide Description Bioequivalence based on Losartan AUC0-t.
Time Frame Blood samples collected over a 48 hour period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Losartan/HCTZ (Test) Hyzaar® (Reference)
Hide Arm/Group Description:
100/25 mg Losartan potassium/Hydrochlorothiazide test product dosed in either period.
100/25 mg Hyzaar® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 76 76
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
959.41  (480.988) 939.492  (465.001)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Losartan/HCTZ (Test), Hyzaar® (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
Confidence Interval (2-Sided) 90%
98.8 to 106
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 Losartan(Area Under the Concentration-time Curve From Time Zero to Infinity)
Hide Description Bioequivalence based on Losartan AUC0-inf.
Time Frame Blood samples collected over a 48 hour period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Losartan/HCTZ (Test) Hyzaar® (Reference)
Hide Arm/Group Description:
100/25 mg Losartan potassium/Hydrochlorothiazide test product dosed in either period.
100/25 mg Hyzaar® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 76 76
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
957.445  (465.781) 956.046  (467.567)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Losartan/HCTZ (Test), Hyzaar® (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 101
Confidence Interval (2-Sided) 90%
98.6 to 104
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 Hydrochlorothiazide(Maximum Observed Concentration of Drug Substance in Plasma)
Hide Description Bioequivalence based on Hydrochlorothiazide Cmax.
Time Frame Blood samples collected over a 48 hour period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Losartan/HCTZ (Test) Hyzaar® (Reference)
Hide Arm/Group Description:
100/25 mg Losartan potassium/Hydrochlorothiazide test product dosed in either period.
100/25 mg Hyzaar® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 76 76
Mean (Standard Deviation)
Unit of Measure: ng/mL
136.361  (33.311) 132.717  (35.468)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Losartan/HCTZ (Test), Hyzaar® (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
Confidence Interval (2-Sided) 90%
98.8 to 108
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 Hydrochlorothiazide(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Hide Description Bioequivalence based on Hydrochlorothiazide AUC0-t.
Time Frame Blood samples collected over a 48 hour period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Losartan/HCTZ (Test) Hyzaar® (Reference)
Hide Arm/Group Description:
100/25 mg Losartan potassium/Hydrochlorothiazide test product dosed in either period.
100/25 mg Hyzaar® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 76 76
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
917.034  (212.109) 919.631  (210.684)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Losartan/HCTZ (Test), Hyzaar® (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 99.7
Confidence Interval (2-Sided) 95%
98.6 to 101
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 Hydrochlorothiazide(Area Under the Concentration-time Curve From Time Zero to Infinity)
Hide Description Bioequivalence based on Hydrochlorothiazide AUC0-inf.
Time Frame Blood samples collected over a 48 hour period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants that completed the study had their samples analyzed.
Arm/Group Title Losartan/HCTZ (Test) Hyzaar® (Reference)
Hide Arm/Group Description:
100/25 mg Losartan potassium/Hydrochlorothiazide test product dosed in either period.
100/25 mg Hyzaar® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 76 76
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
943.22  (217.842) 945.592  (217.269)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Losartan/HCTZ (Test), Hyzaar® (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 99.7
Confidence Interval (2-Sided) 90%
98.7 to 101
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 2 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 Losartan/HCTZ (Test) Hyzaar® (Reference)
Hide Arm/Group Description 100/25 mg Losartan potassium/Hydrochlorothiazide test product dosed in either period. 100/25 mg Hyzaar® Tablets reference product dosed in either period.
All-Cause Mortality
Losartan/HCTZ (Test) Hyzaar® (Reference)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Losartan/HCTZ (Test) Hyzaar® (Reference)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/80 (0.00%)   0/80 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Losartan/HCTZ (Test) Hyzaar® (Reference)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/80 (0.00%)   0/80 (0.00%) 
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
Name/Title: Associate Director, Biopharmaceutics
Organization: TEVA Pharmaceuticals, USA
Phone: 1-866-384-5525
Responsible Party: Associate Director, Biopharmaceutics, Teva Pharmaceuticals USA
ClinicalTrials.gov Identifier: NCT01149473     History of Changes
Other Study ID Numbers: B046515
First Submitted: June 21, 2010
First Posted: June 23, 2010
Results First Submitted: August 16, 2010
Results First Posted: September 14, 2010
Last Update Posted: September 14, 2010