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

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ClinicalTrials.gov Identifier: NCT01149486
Recruitment Status : Completed
First Posted : June 23, 2010
Results First Posted : September 14, 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: Losartan potassium/Hydrochlorothiazide
Drug: Hyzaar®
Enrollment 20
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 Tablets 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 Tablets test product dosed in the second period.
Period Title: First Intervention
Started 10 10
Completed 10 9
Not Completed 0 1
Reason Not Completed
Adverse Event             0             1
Period Title: Washout of 7 Days
Started 10 9
Completed 10 9
Not Completed 0 0
Period Title: Second Intervention
Started 10 9
Completed 10 9
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 Tablets 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 Tablets test product dosed in the second period. Total of all reporting groups
Overall Number of Baseline Participants 10 10 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
10
 100.0%
10
 100.0%
20
 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 10 participants 10 participants 20 participants
Female
2
  20.0%
1
  10.0%
3
  15.0%
Male
8
  80.0%
9
  90.0%
17
  85.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
American Indian 1 1 2
Black 0 1 1
Caucasian 9 8 17
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 10 participants 10 participants 20 participants
10 10 20
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 Tablets test product dosed in either period.
100/25 mg Hyzaar® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 19 19
Mean (Standard Deviation)
Unit of Measure: ng/mL
509.63  (314.75) 538.11  (298.89)
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 93.45
Confidence Interval (2-Sided) 90%
80.20 to 108.88
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 Tablets test product dosed in either period.
100/25 mg Hyzaar® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 19 19
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
866.88  (366.15) 865.00  (362.86)
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 99.45
Confidence Interval (2-Sided) 90%
93.15 to 106.18
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 Tablets test product dosed in either period.
100/25 mg Hyzaar® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 19 19
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
880.15  (368.58) 877.99  (362.75)
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 99.4
Confidence Interval (2-Sided) 90%
93.10 to 106.12
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%.
4.Primary Outcome
Title Cmax of Hydroclorothiazide(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 Tablets test product dosed in either period.
100/25 mg Hyzaar® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 19 19
Mean (Standard Deviation)
Unit of Measure: ng/mL
177.63  (48.09) 161.56  (53.75)
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 111.62
Confidence Interval (2-Sided) 90%
101.47 to 122.79
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%.
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 Tablets test product dosed in either period.
100/25 mg Hyzaar® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 19 19
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
1057.58  (231.26) 1001.54  (236.00)
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 105.8
Confidence Interval (2-Sided) 90%
99.58 to 112.41
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 Tablets test product dosed in either period.
100/25 mg Hyzaar® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 19 19
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
1087.64  (240.82) 1030.73  (238.96)
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 105.55
Confidence Interval (2-Sided) 90%
99.64 to 111.82
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 Losartan Carboxy Acid(Maximum Observed Concentration of Drug Substance in Plasma)
Hide Description Informational comparison of Cmax values for the metabolite Losartan Carboxy Acid.
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 Tablets test product dosed in either period.
100/25 mg Hyzaar® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 19 19
Mean (Standard Deviation)
Unit of Measure: ng/mL
726.85  (210.78) 675.54  (197.25)
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 106.78
Confidence Interval (2-Sided) 90%
98.96 to 115.23
Estimation Comments This analysis was for informational purposes only and was not used to establish bioequivalence.
8.Secondary Outcome
Title AUC0-t of Losartan Carboxy Acid(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Hide Description Informational comparison of AUC0-t values for the metabolite Losartan Carboxy Acid.
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 Tablets test product dosed in either period.
100/25 mg Hyzaar® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 19 19
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
4236.78  (1176.34) 4117.07  (1087.67)
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 102.37
Confidence Interval (2-Sided) 90%
98.75 to 106.14
Estimation Comments This analysis was for informational purposes only and was not used to establish bioequivalence.
9.Secondary Outcome
Title AUC0-inf of Losartan Carboxy Acid(Area Under the Concentration-time Curve From Time Zero to Infinity)
Hide Description Informational comparison of AUC0-inf values for the metabolite Losartan Carboxy Acid.
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 Tablets test product dosed in either period.
100/25 mg Hyzaar® Tablets reference product dosed in either period.
Overall Number of Participants Analyzed 19 19
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
4281.32  (1182.77) 4164.62  (1096.64)
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 102.3
Confidence Interval (2-Sided) 90%
98.72 to 106.01
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 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 Tablets 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 (%) # Events Affected / at Risk (%) # Events
Total   0/20 (0.00%)      0/20 (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 (%) # Events Affected / at Risk (%) # Events
Total   3/20 (15.00%)      6/20 (30.00%)    
General disorders     
Headache * 1  3/20 (15.00%)  3 3/20 (15.00%)  3
Pharyngitis * 1  0/20 (0.00%)  0 1/20 (5.00%)  1
Dizziness * 1  1/20 (5.00%)  1 1/20 (5.00%)  2
Sweaty * 1  1/20 (5.00%)  1 0/20 (0.00%)  0
Purpura * 1  1/20 (5.00%)  1 0/20 (0.00%)  0
Leg Muscles Tight * 1  0/20 (0.00%)  0 1/20 (5.00%)  1
Cut Forearm * 1  0/20 (0.00%)  0 1/20 (5.00%)  1
Fell * 1  0/20 (0.00%)  0 1/20 (5.00%)  1
Confussion * 1  0/20 (0.00%)  0 1/20 (5.00%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
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: NCT01149486     History of Changes
Other Study ID Numbers: R04-080
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: December 8, 2010