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Trial record 27 of 71 for:    TELMISARTAN AND HYDROCHLOROTHIAZIDE

Bioequivalence Study of Telmisartan Between T80/A5/H12.5 mg FDC Tablet and T80/A5 mg Tab and H12.5 mg Tab Concomitant Use

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ClinicalTrials.gov Identifier: NCT02121535
Recruitment Status : Completed
First Posted : April 23, 2014
Results First Posted : April 12, 2017
Last Update Posted : April 12, 2017
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Healthy
Interventions Drug: T80/A5 mg FDC tablet
Drug: H12.5 mg tablet
Drug: T80/A5/H12.5 ng FDC tablet
Drug: H12.5 mf tablet
Drug: T80/A5/H12.5 mg FDC tablet
Enrollment 72
Recruitment Details The trial was performed as an open-label, randomised, single-dose, two-sequence, four period replicated crossover design. A total of 72 healthy male subjects were randomised to 2 groups (Treatment sequences 1 or 2).
Pre-assignment Details  
Arm/Group Title Sequence TRRT Sequence RTTR
Hide Arm/Group Description

Oral administration of study drugs in the following order: T (period 1) - R(period 2) - R (period 3) - T (period 4).

T: telmisartan 80mg+amlodipine 5mg+ hydrochlorothiazide (HCTZ) 12.5mg fix dose tab, once daily; R: telmisartan 80mg+amlodipine 5mg fixed dose combination (FDC) + HCTZ 12.5mg tablet , once daily.

The washout period between drug administrations had to be at least 14 days from the study drug administration of the previous period.

Oral administration of study drugs in the following order: R (period 1) - T (period 2) - T (period 3) - R (period 4).

T: telmisartan 80mg+amlodipine 5mg+HCTZ 12.5mg fix dose tab, once daily; R: telmisartan 80mg+amlodipine 5mg FDC + HCTZ 12.5mg tablet , once daily. The washout period between drug administrations had to be at least 14 days from the study drug administration of the previous period.

Period Title: Period 1 (8 Trial Days)
Started 36 36
Completed 36 35 [1]
Not Completed 0 1
Reason Not Completed
Withdrawal by Subject             0             1
[1]
1 subject withdrew his consent during the washout period between Period 1 and 2.
Period Title: Period 2 (8 Trial Days)
Started 36 35
Completed 36 35
Not Completed 0 0
Period Title: Period 3 (8 Trial Days)
Started 36 35
Completed 35 [1] 35
Not Completed 1 0
Reason Not Completed
Withdrawal by Subject             1             0
[1]
1 subject withdrew consent during the washout period between Period 3 and 4.
Period Title: Period 4 (8 Trial Days)
Started 35 35
Completed 35 35
Not Completed 0 0
Arm/Group Title Sequence TRRT Sequence RTTR Total
Hide Arm/Group Description

Oral administration of study drugs in the following order: T (period 1) - R(period 2) - R (period 3) - T (period 4).

T: telmisartan 80mg+amlodipine 5mg+ hydrochlorothiazide (HCTZ) 12.5mg fix dose tab, once daily; R: telmisartan 80mg+amlodipine 5mg fixed dose combination (FDC) + HCTZ 12.5mg tablet , once daily.

The washout period between drug administrations had to be at least 14 days from the study drug administration of the previous period.

Oral administration of study drugs in the following order: R (period 1) - T (period 2) - T (period 3) - R (period 4). T: telmisartan 80mg+amlodipine 5mg+HCTZ 12.5mg fix dose tab, once daily; R: telmisartan 80mg+amlodipine 5mg FDC + HCTZ 12.5mg tablet , once daily. The washout period between drug administrations had to be at least 14 days from the study drug administration of the previous period. Total of all reporting groups
Overall Number of Baseline Participants 36 36 72
Hide Baseline Analysis Population Description
Treated set (TS): TS included all subjects who were dispensed with the study drugs and were documented to have taken at least 1 dose of the study drugs. Safety analyses were conducted on the TS.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 36 participants 36 participants 72 participants
26.3  (4.7) 27.2  (5.0) 26.7  (4.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 36 participants 72 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
36
 100.0%
36
 100.0%
72
 100.0%
1.Primary Outcome
Title Area Under the Concentration-time Curve of the Telmisartan in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point (AUC0-tz)
Hide Description Area under the concentration-time curve of the telmisartan in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz)
Time Frame 3hours(h) before drug administration and 15minutes (m), 30m, 45m, 1h, 1h30m, 2h, 2h30m, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h, 72h after drug administration
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Hide Analysis Population Description

Pharmacokinetic set (PKS):

included all subjects in the TS who had evaluable pharmacokinetic (PK) variables for both test drug and reference drugs. Subjects who had an important protocol violation (PV) for relevant PK evaluation were excluded from the PKS.

Arm/Group Title Test Treatment Reference Treatment
Hide Arm/Group Description:
Oral administration of telmisartan 80mg+amlodipine 5mg+HCTZ 12.5mg fixed dose combination (FDC), once daily;
Oral administration of telmisartan 80mg+amlodipine 5mg FDC + HCTZ 12.5mg tablet , once daily.
Overall Number of Participants Analyzed 71 71
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
2850
(52.0%)
2790
(54.9%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Test Treatment, Reference Treatment
Comments The statistical model used for the analysis of AUC0-tz was a mixed effect model on the logarithmic scale.
Type of Statistical Test Non-Inferiority or Equivalence
Comments To determine whether the 2-sided 90% confidence interval (CI) for the intra-subject ratio of the AUC0-tz were contained in the acceptance range of 80% to 125% for bioequivalence.
Method of Estimation Estimation Parameter Adjusted Mean Ratio
Estimated Value 101.97
Confidence Interval (2-Sided) 90%
98.94 to 105.08
Estimation Comments Adjusted Mean Ratio (Test/Reference)
2.Primary Outcome
Title Cmax for Telmisartan
Hide Description Cmax (maximum measured concentration of the analyte in plasma)
Time Frame 3hours(h) before drug administration and 15minutes (m), 30m, 45m, 1h, 1h30m, 2h, 2h30m, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h, 72h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Test Treatment Reference Treatment
Hide Arm/Group Description:
Oral administration of telmisartan 80mg+amlodipine 5mg+HCTZ 12.5mg fixed dose combination (FDC), once daily;
Oral administration of telmisartan 80mg+amlodipine 5mg FDC + HCTZ 12.5mg tablet , once daily.
Overall Number of Participants Analyzed 71 71
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
718
(56.4%)
694
(55.2%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Test Treatment, Reference Treatment
Comments The statistical model used for the analysis of Cmax was a mixed effect model on the logarithmic scale.
Type of Statistical Test Non-Inferiority or Equivalence
Comments To determine whether the 2-sided 90% CI for the intra-subject ratio of the Cmax were contained in the acceptance range of 80% to 125% for bioequivalence.
Method of Estimation Estimation Parameter Adjusted Mean Ratio
Estimated Value 103.77
Confidence Interval (2-Sided) 90%
97.03 to 110.99
Estimation Comments Adjusted Mean Ratio (Test/Reference)
3.Primary Outcome
Title AUC0-tz for Amlodipine
Hide Description AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)
Time Frame 3hours(h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h, 72h, 96h, 120h, 144h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Test Treatment Reference Treatment
Hide Arm/Group Description:
Oral administration of telmisartan 80mg+amlodipine 5mg+HCTZ 12.5mg fixed dose combination (FDC), once daily;
Oral administration of telmisartan 80mg+amlodipine 5mg FDC + HCTZ 12.5mg tablet , once daily.
Overall Number of Participants Analyzed 71 71
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
171
(24.3%)
172
(25.0%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Test Treatment, Reference Treatment
Comments The statistical model used for the analysis of AUC0-tz was a mixed effect model on the logarithmic scale.
Type of Statistical Test Non-Inferiority or Equivalence
Comments To determine whether the 2-sided 90% CI for the intra-subject ratio of the AUC0-tz were contained in the acceptance range of 80% to 125% for bioequivalence.
Method of Estimation Estimation Parameter Adjusted Mean Ratio
Estimated Value 99.50
Confidence Interval (2-Sided) 90%
98.08 to 100.94
Estimation Comments Adjusted Mean Ratio (Test/Reference)
4.Primary Outcome
Title Cmax for Amlodipine
Hide Description Cmax (maximum measured concentration of the analyte in plasma)
Time Frame 3hours(h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h, 72h, 96h, 120h, 144h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Test Treatment Reference Treatment
Hide Arm/Group Description:
Oral administration of telmisartan 80mg+amlodipine 5mg+HCTZ 12.5mg fixed dose combination (FDC), once daily;
Oral administration of telmisartan 80mg+amlodipine 5mg FDC + HCTZ 12.5mg tablet , once daily.
Overall Number of Participants Analyzed 71 71
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
3.69
(22.0%)
3.68
(20.7%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Test Treatment, Reference Treatment
Comments The statistical model used for the analysis of Cmax was a mixed effect model on the logarithmic scale.
Type of Statistical Test Non-Inferiority or Equivalence
Comments To determine whether the 2-sided 90% CI for the intra-subject ratio of the Cmax were contained in the acceptance range of 80% to 125% for bioequivalence.
Method of Estimation Estimation Parameter Adjusted Mean Ratio
Estimated Value 100.07
Confidence Interval (2-Sided) 90%
98.45 to 101.72
Estimation Comments Adjusted Mean Ratio (Test/Reference)
5.Primary Outcome
Title Cmax for Hydrochlorothiazide
Hide Description Cmax (maximum measured concentration of the analyte in plasma)
Time Frame 3hours(h) before drug administration and 15minutes (m), 30m, 45m, 1h, 1h30m, 2h, 2h30m, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Test Treatment Reference Treatment
Hide Arm/Group Description:
Oral administration of telmisartan 80mg+amlodipine 5mg+HCTZ 12.5mg fixed dose combination (FDC), once daily;
Oral administration of telmisartan 80mg+amlodipine 5mg FDC + HCTZ 12.5mg tablet , once daily.
Overall Number of Participants Analyzed 71 71
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
104
(23.0%)
94.7
(23.4%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Test Treatment, Reference Treatment
Comments The statistical model used for the analysis of Cmax was a mixed effect model on the logarithmic scale.
Type of Statistical Test Non-Inferiority or Equivalence
Comments To determine whether the 2-sided 90% CI for the intra-subject ratio of the Cmax were contained in the acceptance range of 80% to 125% for bioequivalence.
Method of Estimation Estimation Parameter Adjusted Mean Ratio
Estimated Value 110.16
Confidence Interval (2-Sided) 90%
106.87 to 113.54
Estimation Comments Adjusted Mean Ratio (Test/Reference)
6.Primary Outcome
Title AUC0-tz for Hydrochlorothiazide
Hide Description AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)
Time Frame 3hours(h) before drug administration and 15minutes (m), 30m, 45m, 1h, 1h30m, 2h, 2h30m, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Test Treatment Reference Treatment
Hide Arm/Group Description:
Oral administration of telmisartan 80mg+amlodipine 5mg+HCTZ 12.5mg fixed dose combination (FDC), once daily;
Oral administration of telmisartan 80mg+amlodipine 5mg FDC + HCTZ 12.5mg tablet , once daily.
Overall Number of Participants Analyzed 71 71
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
638
(19.3%)
611
(19.6%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Test Treatment, Reference Treatment
Comments The statistical model used for the analysis of AUC0-tz was a mixed effect model on the logarithmic scale.
Type of Statistical Test Non-Inferiority or Equivalence
Comments To determine whether the 2-sided 90% CI for the intra-subject ratio of the AUC0-tz were contained in the acceptance range of 80% to 125% for bioequivalence.
Method of Estimation Estimation Parameter Adjusted Mean Ratio
Estimated Value 104.30
Confidence Interval (2-Sided) 90%
102.53 to 106.10
Estimation Comments Adjusted Mean Ratio (Test/Reference)
7.Secondary Outcome
Title AUC0-∞ for Telmisartan
Hide Description AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Time Frame 3hours(h) before drug administration and 15minutes (m), 30m, 45m, 1h, 1h30m, 2h, 2h30m, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h, 72h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Test Treatment Reference Treatment
Hide Arm/Group Description:
Oral administration of telmisartan 80mg+amlodipine 5mg+HCTZ 12.5mg fixed dose combination (FDC), once daily;
Oral administration of telmisartan 80mg+amlodipine 5mg FDC + HCTZ 12.5mg tablet , once daily.
Overall Number of Participants Analyzed 71 71
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
3090
(54.5%)
3120
(58.8%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Test Treatment, Reference Treatment
Comments The statistical model used for the analysis of AUC0--∞ was a mixed effect model on the logarithmic scale.
Type of Statistical Test Non-Inferiority or Equivalence
Comments To determine whether the 2-sided 90% CI for the intra-subject ratio of the AUC0-∞ were contained in the acceptance range of 80% to 125% for bioequivalence.
Method of Estimation Estimation Parameter Adjusted Mean Ratio
Estimated Value 100.24
Confidence Interval (2-Sided) 90%
96.80 to 103.80
Estimation Comments Adjusted Mean Ratio (Test/Reference)
8.Secondary Outcome
Title AUC0-∞ for Amlodipine
Hide Description AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Time Frame 3hours(h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h, 72h, 96h, 120h, 144h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Test Treatment Reference Treatment
Hide Arm/Group Description:
Oral administration of telmisartan 80mg+amlodipine 5mg+HCTZ 12.5mg fixed dose combination (FDC), once daily;
Oral administration of telmisartan 80mg+amlodipine 5mg FDC + HCTZ 12.5mg tablet , once daily.
Overall Number of Participants Analyzed 71 71
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
184
(25.2%)
185
(26.0%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Test Treatment, Reference Treatment
Comments The statistical model used for the analysis of AUC0--∞ was a mixed effect model on the logarithmic scale.
Type of Statistical Test Non-Inferiority or Equivalence
Comments To determine whether the 2-sided 90% CI for the intra-subject ratio of the AUC0-∞ were contained in the acceptance range of 80% to 125% for bioequivalence.
Method of Estimation Estimation Parameter Adjusted Mean Ratio
Estimated Value 99.42
Confidence Interval (2-Sided) 90%
97.94 to 100.93
Estimation Comments Adjusted Mean Ratio (Test/Reference)
9.Secondary Outcome
Title AUC0-∞ for Hydrochlorothiazide
Hide Description AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Time Frame 3hours(h) before drug administration and 15minutes (m), 30m, 45m, 1h, 1h30m, 2h, 2h30m, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Test Treatment Reference Treatment
Hide Arm/Group Description:
Oral administration of telmisartan 80mg+amlodipine 5mg+HCTZ 12.5mg fixed dose combination (FDC), once daily;
Oral administration of telmisartan 80mg+amlodipine 5mg FDC + HCTZ 12.5mg tablet , once daily.
Overall Number of Participants Analyzed 71 71
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
661
(18.7%)
634
(18.9%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Test Treatment, Reference Treatment
Comments The statistical model used for the analysis of AUC0--∞ was a mixed effect model on the logarithmic scale.
Type of Statistical Test Non-Inferiority or Equivalence
Comments To determine whether the 2-sided 90% CI for the intra-subject ratio of the AUC0-∞ were contained in the acceptance range of 80% to 125% for bioequivalence.
Method of Estimation Estimation Parameter Adjusted Mean Ratio
Estimated Value 104.37
Confidence Interval (2-Sided) 90%
102.68 to 106.10
Estimation Comments Adjusted Mean Ratio (Test/Reference)
Time Frame Adverse Events occurring after the first study drug administration till the end of treatment (EOT) (EOT: 144 hours after drug administration)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Test Treatment Reference Treatment Total (All Patients)
Hide Arm/Group Description Oral administration of telmisartan 80mg+amlodipine 5mg+HCTZ 12.5mg fixed dose combination (FDC), once daily; Oral administration of telmisartan 80mg+amlodipine 5mg FDC + HCTZ 12.5mg tablet , once daily. Total of all the participants analyzed
All-Cause Mortality
Test Treatment Reference Treatment Total (All Patients)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Test Treatment Reference Treatment Total (All Patients)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/71 (0.00%)   0/72 (0.00%)   0/72 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Test Treatment Reference Treatment Total (All Patients)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/71 (0.00%)   0/72 (0.00%)   0/72 (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.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI’s intellectual property rights
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
Phone: 800-243-0127 ext +1
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02121535     History of Changes
Other Study ID Numbers: 1348.3
First Submitted: April 22, 2014
First Posted: April 23, 2014
Results First Submitted: October 6, 2016
Results First Posted: April 12, 2017
Last Update Posted: April 12, 2017