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Trial record 2 of 948 for:    tablet | Japan

Bioequivalence Study of Telmisartan Between Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg (T80/A5/H12.5 mg) Fixed-dose Combination (FDC) Tablet and T80/H12.5 mg Tab and A5 mg (Encap A2.5 mg Tab x2) Concomitant Use

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ClinicalTrials.gov Identifier: NCT02129192
Recruitment Status : Completed
First Posted : May 2, 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: Amlodipine 5mg capsule
Drug: T80/H12.5 mg FDC tablet
Drug: T80/A5/H12.5 mg FDC tablet
Enrollment 72
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Sequence TRRTT Sequence RTTR
Hide Arm/Group Description

Subjects were treated with telmisartan 80 mg (T80), amlodipine 5 mg (A5) and hydrochlorothiazide (HCTZ) 12.5 mg (H12.5 mg) in the following order from period 1 to period 5:

T (test product: T80/A5/H12.5 mg fixed dose combination (FDC) tablet) - R (reference products: T80/H12.5 mg FDC tablet and A5 mg capsule) - R - T - T.

Treatment periods 1 to 4 were administered following an overnight fast of at least 10 hours, in treatment period 5 after an overnight fast of at least 10 hours, a Japanese-style breakfast was served 30 minutes before drug administration

Subjects were treated telmisartan 80 mg (T80), amlodipine 5 mg (A5) and hydrochlorothiazide (HCTZ) 12.5 mg (H12.5 mg) in the following order from period 1 to period 4:

R - T - T - R.

The treatments were administered following an overnight fast of at least 10 hours.

Period Title: Period 1 Including Washout Period
Started 36 36
Completed 36 35 [1]
Not Completed 0 1
Reason Not Completed
Withdrawal by Subject             0             1
[1]
Withdrawal by one subject in washout period
Period Title: Period 2 Including Washout Period
Started 36 35
Completed 36 35
Not Completed 0 0
Period Title: Period 3 Including Washout Period
Started 36 35
Completed 36 35
Not Completed 0 0
Period Title: Period 4 Including Washout Period
Started 36 35
Completed 36 35
Not Completed 0 0
Period Title: Period 5
Started 36 0 [1]
Completed 36 0
Not Completed 0 0
[1]
This sequence consists of only 4 periods.
Arm/Group Title Sequence TRRTT Sequence RTTR Total
Hide Arm/Group Description

Subjects were treated with telmisartan 80 mg (T80), amlodipine 5 mg (A5) and hydrochlorothiazide (HCTZ) 12.5 mg (H12.5 mg) in the following order from period 1 to period 5:

T (test product: T80/A5/H12.5 mg fixed dose combination (FDC) tablet) - R (reference products: T80/H12.5 mg FDC tablet and A5 mg capsule) - R - T - T.

Treatment periods 1 to 4 were administered following an overnight fast of at least 10 hours, in treatment period 5 after an overnight fast of at least 10 hours, a Japanese-style breakfast was served 30 minutes before drug administration

Subjects were treated telmisartan 80 mg (T80), amlodipine 5 mg (A5) and hydrochlorothiazide (HCTZ) 12.5 mg (H12.5 mg) in the following order from period 1 to period 4:

R - T - T - R.

The treatments were administered following an overnight fast of at least 10 hours.

Total of all reporting groups
Overall Number of Baseline Participants 36 36 72
Hide Baseline Analysis Population Description
Treated Set (TS): This subject set included all subjects who were dispensed the study drug and were documented to have taken at least one dose of the study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 36 participants 36 participants 72 participants
26.6  (4.2) 26.6  (3.9) 26.6  (4.0)
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 Maximum Measured Concentration (Cmax) of the Analytes in Plasma
Hide Description Maximum measured concentration (Cmax) of telmisartan, amlodipine and HCTZ in plasma
Time Frame 3 hours (h) pre drug admin and 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h after drug admin, in addition 15min, 30min, 45min, 1h 30min, 2h 30min for telmisartan and HCTZ only, 72h for telmisartan and amlodipine only and 96h, 120h, 144h for amlodipine only
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic set (PKS) which included all healthy subjects in the TS who had evaluable PK variables for both treatments (i.e. had data of at least one analyte for both test and reference products) in periods 1, 2, 3 and 4. Subjects who had an important protocol violation relevant to PK evaluation were to be excluded from the PKS.
Arm/Group Title T80/A5/H12.5 mg FDC T80/H12.5 FDC + A5 Capsule
Hide Arm/Group Description:
Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet
Telmisartan 80 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet and Amlodipine 5 mg capsule
Overall Number of Participants Analyzed 71 71
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Telmisartan
697
(75.5%)
726
(74.9%)
Amlodipine
3.62
(20.2%)
3.57
(19.9%)
HCTZ
98.5
(25.1%)
96.6
(25.8%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection T80/A5/H12.5 mg FDC, T80/H12.5 FDC + A5 Capsule
Comments Adjusted by−treatment means on the log−transformed scale for telmisartan 80 mg
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence was established by using the average bioequivalence method and by ensuring that the ratio of Cmax of the two treatments was within the pre-specified acceptance range (80%-125%)
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model on logarithmic scale included "subjects within sequence” as random effect and “sequence”, “period”, and “treatment” as fixed effects.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 95.77
Confidence Interval (2-Sided) 90%
88.89 to 103.17
Estimation Comments Ratio calculated as T80/A5/H12.5 mg FDC divided by T80/H12.5 FDC + A5 mono.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection T80/A5/H12.5 mg FDC, T80/H12.5 FDC + A5 Capsule
Comments Adjusted by−treatment means on the log−transformed scale for amlodipine 5 mg
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence was established by using the average bioequivalence method and by ensuring that the ratio of Cmax of the two treatments was within the pre-specified acceptance range (80%-125%)
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model on logarithmic scale included “subjects within sequence” as random effect and “sequence”, “period”, and “treatment” as fixed effects.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 101.40
Confidence Interval (2-Sided) 90%
99.70 to 103.13
Estimation Comments Ratio calculated as T80/A5/H12.5 mg FDC divided by T80/H12.5 FDC + A5 mono.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection T80/A5/H12.5 mg FDC, T80/H12.5 FDC + A5 Capsule
Comments Adjusted by−treatment means on the log−transformed scale for hydrochlorothiazide 12.5 mg
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence was established by using the average bioequivalence method and by ensuring that the ratio of Cmax of the two treatments was within the pre-specified acceptance range (80%-125%)
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model on logarithmic scale included “subjects within sequence” as random effect and “sequence”, “period”, and “treatment” as fixed effects.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 101.77
Confidence Interval (2-Sided) 90%
98.46 to 105.19
Estimation Comments Ratio calculated as T80/A5/H12.5 mg FDC divided by T80/H12.5 FDC + A5 mono.
2.Primary Outcome
Title Maximum Measured Concentration (Cmax) of the Analytes in Plasma After Single Administration of T80/A5/H12.5 mg FDC Tablet
Hide Description Maximum measured concentration (Cmax) of telmisartan, amlodipine and HCTZ in plasma after single oral administration of T80/A5/H12.5 mg FDC tablet
Time Frame 3 hours (h) pre drug admin and 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h after drug admin, in addition 15min, 30min, 45min, 1h 30min, 2h 30min for telmisartan and HCTZ only, 72h for telmisartan and amlodipine only and 96h, 120h, 144h for amlodipine only
Hide Outcome Measure Data
Hide Analysis Population Description
Food effect analysis set (FEAS) which included healthy subjects of treatment sequence TRRTT in the TS who were judged appropriate to continue to period 5 by the investigator, had evaluable PK variables for both feeding conditions and did not have an important protocol violation relevant to relative bioavailability evaluation.
Arm/Group Title T80/A5/H12.5 mg FDC Fed T80/A5/H12.5 FDC Fasted
Hide Arm/Group Description:
Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet in fed condition
Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet in fasted condition
Overall Number of Participants Analyzed 36 36
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Telmisartan
182
(75.9%)
605
(84.4%)
Amlodipine
3.54
(20.6%)
3.60
(22.4%)
HCTZ
75.4
(16.5%)
94.6
(20.1%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection T80/A5/H12.5 mg FDC Fed, T80/A5/H12.5 FDC Fasted
Comments Adjusted by−treatment geometric means for telmisartan 80 mg. No hypothesis was tested.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method ANOVA
Comments Model included “subject” as random effect and “feeding condition” as fixed effect.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 30.15
Confidence Interval (2-Sided) 90%
24.99 to 36.38
Estimation Comments Ratio calculated as T80/A5/H12.5 mg FDC Fed divided by T80/A5/H12.5 mg FDC Fasted.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection T80/A5/H12.5 mg FDC Fed, T80/A5/H12.5 FDC Fasted
Comments Adjusted by−treatment geometric means for amlodipine 5 mg. No hypothesis was tested.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments Model included “subject” as random effect and “feeding condition” as fixed effect.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 98.23
Confidence Interval (2-Sided) 90%
94.63 to 101.97
Estimation Comments Ratio calculated as T80/A5/H12.5 mg FDC Fed divided by T80/A5/H12.5 mg FDC Fasted.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection T80/A5/H12.5 mg FDC Fed, T80/A5/H12.5 FDC Fasted
Comments Adjusted by−treatment geometric means for hydrochlorothiazide 12.5 mg. No hypothesis was tested.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5422
Comments [Not Specified]
Method ANOVA
Comments Model included “subject” as random effect and “feeding condition” as fixed effect.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 79.69
Confidence Interval (2-Sided) 90%
74.97 to 84.71
Estimation Comments Ratio calculated as T80/A5/H12.5 mg FDC Fed divided by T80/A5/H12.5 mg FDC Fasted.
3.Primary Outcome
Title Area Under the Concentration-time Curve (AUC 0-tz) of the Analytes in Plasma Over the Time Interval From 0 to the Last Quantifiable Plasma Concentration
Hide Description Area under the concentration-time curve (AUC 0-tz) of telmisartan, amlodipine and HCTZ in plasma over the time interval from 0 to the last quantifiable plasma concentration
Time Frame 3 hours (h) pre drug admin and 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h after drug admin, in addition 15min, 30min, 45min, 1h 30min, 2h 30min for telmisartan and HCTZ only, 72h for telmisartan and amlodipine only and 96h, 120h, 144h for amlodipine only
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title T80/A5/H12.5 mg FDC T80/H12.5 FDC + A5 Capsule
Hide Arm/Group Description:
Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet
Telmisartan 80 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet and Amlodipine 5 mg capsule
Overall Number of Participants Analyzed 71 71
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
Telmisartan
2580
(76.8%)
2600
(76.1%)
Amlodipine
159
(23.4%)
157
(24.0%)
HCTZ
600
(21.0%)
598
(19.1%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection T80/A5/H12.5 mg FDC, T80/H12.5 FDC + A5 Capsule
Comments Adjusted by−treatment means on the log−transformed scale for telmisartan 80 mg
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence was established by using the average bioequivalence method and by ensuring that the ratio of AUC 0-tz of the two treatments was within the pre-specified acceptance range (80%-125%)
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model on logarithmic scale included “subjects within sequence” as random effect and “sequence”, “period”, and “treatment” as fixed effects.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 99.21
Confidence Interval (2-Sided) 90%
96.14 to 102.38
Estimation Comments Ratio calculated as T80/A5/H12.5 mg FDC divided by T80/H12.5 FDC + A5 mono.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection T80/A5/H12.5 mg FDC, T80/H12.5 FDC + A5 Capsule
Comments Adjusted by−treatment means on the log−transformed scale for amlodipine 5 mg
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence was established by using the average bioequivalence method and by ensuring that the ratio of AUC 0-tz of the two treatments was within the pre-specified acceptance range (80%-125%)
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model on logarithmic scale included “subjects within sequence” as random effect and “sequence”, “period”, and “treatment” as fixed effects.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 101.43
Confidence Interval 90%
99.84 to 103.04
Estimation Comments Ratio calculated as T80/A5/H12.5 mg FDC divided by T80/H12.5 FDC + A5 mono.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection T80/A5/H12.5 mg FDC, T80/H12.5 FDC + A5 Capsule
Comments Adjusted by−treatment means on the log−transformed scale for hydrochlorothiazide 12.5 mg
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence was established by using the average bioequivalence method and by ensuring that the ratio of AUC 0-tz of the two treatments was within the pre-specified acceptance range (80%-125%)
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model on logarithmic scale included “subjects within sequence” as random effect and “sequence”, “period”, and “treatment” as fixed effects.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 100.33
Confidence Interval (2-Sided) 90%
98.29 to 102.40
Estimation Comments Ratio calculated as T80/A5/H12.5 mg FDC divided by T80/H12.5 FDC + A5 mono.
4.Primary Outcome
Title Area Under the Concentration-time Curve (AUC 0-tz) of the Analytes in Plasma Over the Time Interval From 0 to the Last Quantifiable Plasma Concentration After Single Administration of T80/A5/H12.5 mg FDC Tablet
Hide Description Area under the concentration-time curve (AUC 0-tz) of telmisartan, amlodipine and HCTZ in plasma over the time interval from 0 to the last quantifiable plasma concentration after single administration of T80/A5/H12.5 mg FDC tablet
Time Frame 3 hours (h) pre drug admin and 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h after drug admin, in addition 15min, 30min, 45min, 1h 30min, 2h 30min for telmisartan and HCTZ only, 72h for telmisartan and amlodipine only and 96h, 120h, 144h for amlodipine only
Hide Outcome Measure Data
Hide Analysis Population Description
FEAS
Arm/Group Title T80/A5/H12.5 mg FDC Fed T80/A5/H12.5 FDC Fasted
Hide Arm/Group Description:
Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet in fed condition
Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet in fasted condition
Overall Number of Participants Analyzed 36 36
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
Telmisartan
1500
(98.3%)
2350
(93.6%)
Amlodipine
156
(23.9%)
157
(26.1%)
HCTZ
515
(18.9%)
575
(19.2%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection T80/A5/H12.5 mg FDC Fed, T80/A5/H12.5 FDC Fasted
Comments Adjusted by−treatment geometric means for telmisartan 80 mg. No hypothesis was tested.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method ANOVA
Comments Model included “subject” as random effect and “feeding condition” as fixed effect.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 63.66
Confidence Interval (2-Sided) 90%
58.98 to 68.71
Estimation Comments Ratio calculated as T80/A5/H12.5 mg FDC Fed divided by T80/A5/H12.5 mg FDC Fasted.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection T80/A5/H12.5 mg FDC Fed, T80/A5/H12.5 FDC Fasted
Comments Adjusted by−treatment geometric means for amlodipine 5 mg. No hypothesis was tested.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments Model included “subject” as random effect and “feeding condition” as fixed effect.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 99.74
Confidence Interval (2-Sided) 90%
97.08 to 102.48
Estimation Comments Ratio calculated as T80/A5/H12.5 mg FDC Fed divided by T80/A5/H12.5 mg FDC Fasted.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection T80/A5/H12.5 mg FDC Fed, T80/A5/H12.5 FDC Fasted
Comments Adjusted by−treatment geometric means for hydrochlorothiazide 12.5 mg. No hypothesis was tested.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANOVA
Comments Model included “subject” as random effect and “feeding condition” as fixed effect.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 89.66
Confidence Interval (2-Sided) 90%
85.80 to 93.70
Estimation Comments Ratio calculated as T80/A5/H12.5 mg FDC Fed divided by T80/A5/H12.5 mg FDC Fasted.
5.Secondary Outcome
Title Area Under the Concentration-time Curve (AUC 0-infinity) of the Analytes in Plasma Over the Time Interval From 0 to Extrapolated Infinity
Hide Description Area under the concentration-time curve (AUC 0-infinity) of telmisartan, amlodipine and HCTZ in plasma over the time interval from 0 to extrapolated infinity
Time Frame 3 hours (h) pre drug admin and 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h after drug admin, in addition 15min, 30min, 45min, 1h 30min, 2h 30min for telmisartan and HCTZ only, 72h for telmisartan and amlodipine only and 96h, 120h, 144h for amlodipine only
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title T80/A5/H12.5 mg FDC T80/H12.5 FDC + A5 Capsule
Hide Arm/Group Description:
Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet
Telmisartan 80 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet and Amlodipine 5 mg capsule
Overall Number of Participants Analyzed 71 71
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
Telmisartan ( N = 142, 142)
2750
(79.2%)
2730
(73.7%)
Amlodipine ( N = 142, 142)
172
(25.4%)
170
(26.0%)
HCTZ ( N = 141, 142)
626
(20.2%)
624
(18.2%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection T80/A5/H12.5 mg FDC, T80/H12.5 FDC + A5 Capsule
Comments Adjusted by−treatment means on the log−transformed scale for telmisartan 80 mg
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence was established by using the average bioequivalence method and by ensuring that the ratio of AUC 0-inf of the two treatments was within the pre-specified acceptance range (80%-125%).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model on logarithmic scale included “subjects within sequence” as random effect and “sequence”, “period”, and “treatment” as fixed effects.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 99.62
Confidence Interval (2-Sided) 90%
96.32 to 103.04
Estimation Comments Ratio calculated as T80/A5/H12.5 mg FDC divided by T80/H12.5 FDC + A5 mono.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection T80/A5/H12.5 mg FDC, T80/H12.5 FDC + A5 Capsule
Comments Adjusted by−treatment means on the log−transformed scale for amlodipine 5 mg
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence was established by using the average bioequivalence method and by ensuring that the ratio of AUC 0-inf of the two treatments was within the pre-specified acceptance range (80%-125%).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model on logarithmic scale included “subjects within sequence” as random effect and “sequence”, “period”, and “treatment” as fixed effects.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 101.21
Confidence Interval (2-Sided) 90%
99.59 to 102.87
Estimation Comments Ratio calculated as T80/A5/H12.5 mg FDC divided by T80/H12.5 FDC + A5 mono.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection T80/A5/H12.5 mg FDC, T80/H12.5 FDC + A5 Capsule
Comments Adjusted by−treatment means on the log−transformed scale for hydrochlorothiazide 12.5 mg
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence was established by using the average bioequivalence method and by ensuring that the ratio of AUC 0-inf of the two treatments was within the pre-specified acceptance range (80%-125%).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model on logarithmic scale included “subjects within sequence” as random effect and “sequence”, “period”, and “treatment” as fixed effects.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 100.15
Confidence Interval (2-Sided) 90%
98.23 to 102.10
Estimation Comments Ratio calculated as T80/A5/H12.5 mg FDC divided by T80/H12.5 FDC + A5 mono.
6.Secondary Outcome
Title Area Under the Concentration-time Curve (AUC 0-infinity) of the Analytes in Plasma Over the Time Interval From 0 to Extrapolated Infinity After Single Administration of T80/A5/H12.5 mg FDC Tablet
Hide Description Area under the concentration-time curve (AUC 0-infinity) of telmisartan, amlodipine and HCTZ in plasma over the time interval from 0 to extrapolated infinity after single administration of T80/A5/H12.5 mg FDC tablet
Time Frame 3 hours (h) pre drug admin and 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h after drug admin, in addition 15min, 30min, 45min, 1h 30min, 2h 30min for telmisartan and HCTZ only, 72h for telmisartan and amlodipine only and 96h, 120h, 144h for amlodipine only
Hide Outcome Measure Data
Hide Analysis Population Description
FEAS
Arm/Group Title T80/A5/H12.5 mg FDC Fed T80/A5/H12.5 FDC Fasted
Hide Arm/Group Description:
Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet in fed condition
Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet in fasted condition
Overall Number of Participants Analyzed 36 36
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
Telmisartan ( N = 35, 36 )
1670
(108.0%)
2530
(98.3%)
Amlodipine ( N = 36, 36 )
168
(26.0%)
169
(28.6%)
HCTZ ( N = 36, 36 )
542
(18.3%)
603
(18.3%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection T80/A5/H12.5 mg FDC Fed, T80/A5/H12.5 FDC Fasted
Comments Adjusted by−treatment geometric means for telmisartan 80 mg. No hypothesis was tested.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method ANOVA
Comments Model included “subject” as random effect and “feeding condition” as fixed effect.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 64.40
Confidence Interval (2-Sided) 90%
59.59 to 69.59
Estimation Comments Ratio calculated as T80/A5/H12.5 mg FDC Fed divided by T80/A5/H12.5 mg FDC Fasted.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection T80/A5/H12.5 mg FDC Fed, T80/A5/H12.5 FDC Fasted
Comments Adjusted by−treatment geometric means for amlodipine 5 mg. No hypothesis was tested.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments Model included “subject” as random effect and “feeding condition” as fixed effect.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 99.45
Confidence Interval (2-Sided) 90%
96.69 to 102.29
Estimation Comments Ratio calculated as T80/A5/H12.5 mg FDC Fed divided by T80/A5/H12.5 mg FDC Fasted.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection T80/A5/H12.5 mg FDC Fed, T80/A5/H12.5 FDC Fasted
Comments Adjusted by−treatment geometric means for hydrochlorothiazide 12.5 mg. No hypothesis was tested.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments Model included “subject” as random effect and “feeding condition” as fixed effect.
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 89.82
Confidence Interval (2-Sided) 90%
86.02 to 93.79
Estimation Comments Ratio calculated as T80/A5/H12.5 mg FDC Fed divided by T80/A5/H12.5 mg FDC Fasted.
Time Frame From first drug administration until end of washout period (14 days) or 144 hours after last drug administration (6 days)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title T80/A5/H12.5 mg FDC T80/H12.5 FDC + A5 Capsule Total.
Hide Arm/Group Description Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet Telmisartan 80 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet and Amlodipine 5 mg capsule All participants randomised into the study.
All-Cause Mortality
T80/A5/H12.5 mg FDC T80/H12.5 FDC + A5 Capsule Total.
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
T80/A5/H12.5 mg FDC T80/H12.5 FDC + A5 Capsule Total.
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%
T80/A5/H12.5 mg FDC T80/H12.5 FDC + A5 Capsule Total.
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/71 (15.49%)   6/72 (8.33%)   16/72 (22.22%) 
Nervous system disorders       
Headache  1  7/71 (9.86%)  4/72 (5.56%)  10/72 (13.89%) 
Vascular disorders       
Orthostatic hypotension  1  4/71 (5.63%)  2/72 (2.78%)  6/72 (8.33%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
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.
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: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02129192     History of Changes
Other Study ID Numbers: 1348.4
First Submitted: April 30, 2014
First Posted: May 2, 2014
Results First Submitted: October 6, 2016
Results First Posted: April 12, 2017
Last Update Posted: April 12, 2017