Trial Outcomes & Findings for 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 (NCT NCT02129192)
NCT ID: NCT02129192
Last Updated: 2017-04-12
Results Overview
Maximum measured concentration (Cmax) of telmisartan, amlodipine and HCTZ in plasma
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
72 participants
Primary outcome timeframe
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
Results posted on
2017-04-12
Participant Flow
Participant milestones
| Measure |
Sequence TRRTT
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
|
Sequence RTTR
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 1 Including Washout Period
STARTED
|
36
|
36
|
|
Period 1 Including Washout Period
COMPLETED
|
36
|
35
|
|
Period 1 Including Washout Period
NOT COMPLETED
|
0
|
1
|
|
Period 2 Including Washout Period
STARTED
|
36
|
35
|
|
Period 2 Including Washout Period
COMPLETED
|
36
|
35
|
|
Period 2 Including Washout Period
NOT COMPLETED
|
0
|
0
|
|
Period 3 Including Washout Period
STARTED
|
36
|
35
|
|
Period 3 Including Washout Period
COMPLETED
|
36
|
35
|
|
Period 3 Including Washout Period
NOT COMPLETED
|
0
|
0
|
|
Period 4 Including Washout Period
STARTED
|
36
|
35
|
|
Period 4 Including Washout Period
COMPLETED
|
36
|
35
|
|
Period 4 Including Washout Period
NOT COMPLETED
|
0
|
0
|
|
Period 5
STARTED
|
36
|
0
|
|
Period 5
COMPLETED
|
36
|
0
|
|
Period 5
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence TRRTT
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
|
Sequence RTTR
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 1 Including Washout Period
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
Sequence TRRTT
n=36 Participants
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
|
Sequence RTTR
n=36 Participants
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
n=72 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
26.6 Years
STANDARD_DEVIATION 4.2 • n=5 Participants
|
26.6 Years
STANDARD_DEVIATION 3.9 • n=7 Participants
|
26.6 Years
STANDARD_DEVIATION 4.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
36 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
72 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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 onlyPopulation: 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.
Maximum measured concentration (Cmax) of telmisartan, amlodipine and HCTZ in plasma
Outcome measures
| Measure |
T80/A5/H12.5 mg FDC
n=71 Participants
Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet
|
T80/H12.5 FDC + A5 Capsule
n=71 Participants
Telmisartan 80 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet and Amlodipine 5 mg capsule
|
|---|---|---|
|
Maximum Measured Concentration (Cmax) of the Analytes in Plasma
Telmisartan
|
697 ng/mL
Geometric Coefficient of Variation 75.5
|
726 ng/mL
Geometric Coefficient of Variation 74.9
|
|
Maximum Measured Concentration (Cmax) of the Analytes in Plasma
Amlodipine
|
3.62 ng/mL
Geometric Coefficient of Variation 20.2
|
3.57 ng/mL
Geometric Coefficient of Variation 19.9
|
|
Maximum Measured Concentration (Cmax) of the Analytes in Plasma
HCTZ
|
98.5 ng/mL
Geometric Coefficient of Variation 25.1
|
96.6 ng/mL
Geometric Coefficient of Variation 25.8
|
PRIMARY outcome
Timeframe: 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 onlyPopulation: 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.
Maximum measured concentration (Cmax) of telmisartan, amlodipine and HCTZ in plasma after single oral administration of T80/A5/H12.5 mg FDC tablet
Outcome measures
| Measure |
T80/A5/H12.5 mg FDC
n=36 Participants
Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet
|
T80/H12.5 FDC + A5 Capsule
n=36 Participants
Telmisartan 80 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet and Amlodipine 5 mg capsule
|
|---|---|---|
|
Maximum Measured Concentration (Cmax) of the Analytes in Plasma After Single Administration of T80/A5/H12.5 mg FDC Tablet
Telmisartan
|
182 ng/mL
Geometric Coefficient of Variation 75.9
|
605 ng/mL
Geometric Coefficient of Variation 84.4
|
|
Maximum Measured Concentration (Cmax) of the Analytes in Plasma After Single Administration of T80/A5/H12.5 mg FDC Tablet
Amlodipine
|
3.54 ng/mL
Geometric Coefficient of Variation 20.6
|
3.60 ng/mL
Geometric Coefficient of Variation 22.4
|
|
Maximum Measured Concentration (Cmax) of the Analytes in Plasma After Single Administration of T80/A5/H12.5 mg FDC Tablet
HCTZ
|
75.4 ng/mL
Geometric Coefficient of Variation 16.5
|
94.6 ng/mL
Geometric Coefficient of Variation 20.1
|
PRIMARY outcome
Timeframe: 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 onlyPopulation: PKS
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
Outcome measures
| Measure |
T80/A5/H12.5 mg FDC
n=71 Participants
Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet
|
T80/H12.5 FDC + A5 Capsule
n=71 Participants
Telmisartan 80 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet and Amlodipine 5 mg capsule
|
|---|---|---|
|
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
Telmisartan
|
2580 ng*h/mL
Geometric Coefficient of Variation 76.8
|
2600 ng*h/mL
Geometric Coefficient of Variation 76.1
|
|
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
Amlodipine
|
159 ng*h/mL
Geometric Coefficient of Variation 23.4
|
157 ng*h/mL
Geometric Coefficient of Variation 24.0
|
|
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
HCTZ
|
600 ng*h/mL
Geometric Coefficient of Variation 21.0
|
598 ng*h/mL
Geometric Coefficient of Variation 19.1
|
PRIMARY outcome
Timeframe: 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 onlyPopulation: FEAS
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
Outcome measures
| Measure |
T80/A5/H12.5 mg FDC
n=36 Participants
Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet
|
T80/H12.5 FDC + A5 Capsule
n=36 Participants
Telmisartan 80 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet and Amlodipine 5 mg capsule
|
|---|---|---|
|
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
Telmisartan
|
1500 ng*h/mL
Geometric Coefficient of Variation 98.3
|
2350 ng*h/mL
Geometric Coefficient of Variation 93.6
|
|
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
Amlodipine
|
156 ng*h/mL
Geometric Coefficient of Variation 23.9
|
157 ng*h/mL
Geometric Coefficient of Variation 26.1
|
|
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
HCTZ
|
515 ng*h/mL
Geometric Coefficient of Variation 18.9
|
575 ng*h/mL
Geometric Coefficient of Variation 19.2
|
SECONDARY outcome
Timeframe: 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 onlyPopulation: PKS
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
Outcome measures
| Measure |
T80/A5/H12.5 mg FDC
n=71 Participants
Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet
|
T80/H12.5 FDC + A5 Capsule
n=71 Participants
Telmisartan 80 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet and Amlodipine 5 mg capsule
|
|---|---|---|
|
Area Under the Concentration-time Curve (AUC 0-infinity) of the Analytes in Plasma Over the Time Interval From 0 to Extrapolated Infinity
Telmisartan ( N = 142, 142)
|
2750 ng*h/mL
Geometric Coefficient of Variation 79.2
|
2730 ng*h/mL
Geometric Coefficient of Variation 73.7
|
|
Area Under the Concentration-time Curve (AUC 0-infinity) of the Analytes in Plasma Over the Time Interval From 0 to Extrapolated Infinity
Amlodipine ( N = 142, 142)
|
172 ng*h/mL
Geometric Coefficient of Variation 25.4
|
170 ng*h/mL
Geometric Coefficient of Variation 26.0
|
|
Area Under the Concentration-time Curve (AUC 0-infinity) of the Analytes in Plasma Over the Time Interval From 0 to Extrapolated Infinity
HCTZ ( N = 141, 142)
|
626 ng*h/mL
Geometric Coefficient of Variation 20.2
|
624 ng*h/mL
Geometric Coefficient of Variation 18.2
|
SECONDARY outcome
Timeframe: 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 onlyPopulation: FEAS
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
Outcome measures
| Measure |
T80/A5/H12.5 mg FDC
n=36 Participants
Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet
|
T80/H12.5 FDC + A5 Capsule
n=36 Participants
Telmisartan 80 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet and Amlodipine 5 mg capsule
|
|---|---|---|
|
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
Telmisartan ( N = 35, 36 )
|
1670 ng*h/mL
Geometric Coefficient of Variation 108.0
|
2530 ng*h/mL
Geometric Coefficient of Variation 98.3
|
|
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
Amlodipine ( N = 36, 36 )
|
168 ng*h/mL
Geometric Coefficient of Variation 26.0
|
169 ng*h/mL
Geometric Coefficient of Variation 28.6
|
|
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
HCTZ ( N = 36, 36 )
|
542 ng*h/mL
Geometric Coefficient of Variation 18.3
|
603 ng*h/mL
Geometric Coefficient of Variation 18.3
|
Adverse Events
T80/A5/H12.5 mg FDC
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
T80/H12.5 FDC + A5 Capsule
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Total.
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
T80/A5/H12.5 mg FDC
n=71 participants at risk
Telmisartan 80 mg/Amlodipine 5 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet
|
T80/H12.5 FDC + A5 Capsule
n=72 participants at risk
Telmisartan 80 mg/Hydrochlorothiazide 12.5 mg fixed dose combination tablet and Amlodipine 5 mg capsule
|
Total.
n=72 participants at risk
All participants randomised into the study.
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
9.9%
7/71 • From first drug administration until end of washout period (14 days) or 144 hours after last drug administration (6 days)
|
5.6%
4/72 • From first drug administration until end of washout period (14 days) or 144 hours after last drug administration (6 days)
|
13.9%
10/72 • From first drug administration until end of washout period (14 days) or 144 hours after last drug administration (6 days)
|
|
Vascular disorders
Orthostatic hypotension
|
5.6%
4/71 • From first drug administration until end of washout period (14 days) or 144 hours after last drug administration (6 days)
|
2.8%
2/72 • From first drug administration until end of washout period (14 days) or 144 hours after last drug administration (6 days)
|
8.3%
6/72 • From first drug administration until end of washout period (14 days) or 144 hours after last drug administration (6 days)
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER