Trial Outcomes & Findings for Pharmacokinetics of Different Formulations of Telmisartan, Amlodipine, and Hydrochlorothiazide (HCTZ) in Japanese Healthy Male Volunteers (NCT NCT02183675)
NCT ID: NCT02183675
Last Updated: 2016-11-30
Results Overview
Maximum measured concentration (Cmax) of telmisartan in plasma at steady state over the dosing interval tau
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
36 participants
Primary outcome timeframe
15 minutes (min) before drug administration and 15min, 30min, 45min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h and 72h after 10 days drug administration
Results posted on
2016-11-30
Participant Flow
An open-label, randomised, six-sequence crossover design. Each participant received three treatments each for 10 days. There was no washout period between treatments.
Participant milestones
| Measure |
T80-A5-H12.5 / T80-H12.5 / T80-A5
Participants received the three treatments, the treatments were administered orally in the following order:
* Telmisartan 80mg/Amlodipine 5mg/ hydrochlorothiazide (HCTZ) 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
* Telmisartan 80mg/ HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
* Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
|
T80-H12.5 / T80-A5 / T80-A5-H12.5
Participants received the three treatments, the treatments were administered orally in the following order:
* Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
* Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
* Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
|
T80-A5 / T80-A5-H12.5 / T80-H12.5
Participants received the three treatments, the treatments were administered orally in the following order:
* Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
* Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
* Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
|
T80-A5 / T80-H12.5 / T80-A5-H12.5
Participants received the three treatments, the treatments were administered orally in the following order:
* Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
* Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
* Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
|
T80-A5-H12.5 / T80-A5 / T80-H12.5
Participants received the three treatments, the treatments were administered orally in the following order:
* Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
* Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
* Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
|
T80-H12.5 / T80-A5-H12.5 / T80-A5
Participants received the three treatments, the treatments were administered orally in the following order:
* Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
* Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
* Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
|
|---|---|---|---|---|---|---|
|
Treatment Period 1 (10 Days)
STARTED
|
6
|
6
|
6
|
6
|
6
|
6
|
|
Treatment Period 1 (10 Days)
COMPLETED
|
6
|
6
|
6
|
6
|
6
|
6
|
|
Treatment Period 1 (10 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 2 (10 Days)
STARTED
|
6
|
6
|
6
|
6
|
6
|
6
|
|
Treatment Period 2 (10 Days)
COMPLETED
|
6
|
6
|
6
|
6
|
6
|
4
|
|
Treatment Period 2 (10 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
2
|
|
Treatment Period 3 (10 Days)
STARTED
|
6
|
6
|
6
|
6
|
6
|
4
|
|
Treatment Period 3 (10 Days)
COMPLETED
|
6
|
6
|
6
|
6
|
6
|
4
|
|
Treatment Period 3 (10 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
T80-A5-H12.5 / T80-H12.5 / T80-A5
Participants received the three treatments, the treatments were administered orally in the following order:
* Telmisartan 80mg/Amlodipine 5mg/ hydrochlorothiazide (HCTZ) 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
* Telmisartan 80mg/ HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
* Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
|
T80-H12.5 / T80-A5 / T80-A5-H12.5
Participants received the three treatments, the treatments were administered orally in the following order:
* Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
* Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
* Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
|
T80-A5 / T80-A5-H12.5 / T80-H12.5
Participants received the three treatments, the treatments were administered orally in the following order:
* Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
* Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
* Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
|
T80-A5 / T80-H12.5 / T80-A5-H12.5
Participants received the three treatments, the treatments were administered orally in the following order:
* Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
* Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
* Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
|
T80-A5-H12.5 / T80-A5 / T80-H12.5
Participants received the three treatments, the treatments were administered orally in the following order:
* Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
* Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
* Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
|
T80-H12.5 / T80-A5-H12.5 / T80-A5
Participants received the three treatments, the treatments were administered orally in the following order:
* Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
* Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
* Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
|
|---|---|---|---|---|---|---|
|
Treatment Period 2 (10 Days)
Adverse Event
|
0
|
0
|
0
|
0
|
0
|
2
|
Baseline Characteristics
Pharmacokinetics of Different Formulations of Telmisartan, Amlodipine, and Hydrochlorothiazide (HCTZ) in Japanese Healthy Male Volunteers
Baseline characteristics by cohort
| Measure |
T80-A5-H12.5 / T80-H12.5 / T80-A5
n=6 Participants
Participants received the three treatments, the treatments were administered orally in the following order:
* Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
* Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
* Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
|
T80-H12.5 / T80-A5 / T80-A5-H12.5
n=6 Participants
Participants received the three treatments, the treatments were administered orally in the following order:
* Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
* Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
* Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
|
T80-A5 / T80-A5-H12.5 / T80-H12.5
n=6 Participants
Participants received the three treatments, the treatments were administered orally in the following order:
* Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
* Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
* Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
|
T80-A5 / T80-H12.5 / T80-A5-H12.5
n=6 Participants
Participants received the three treatments, the treatments were administered orally in the following order:
* Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
* Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
* Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
|
T80-A5-H12.5 / T80-A5 / T80-H12.5
n=6 Participants
Participants received the three treatments, the treatments were administered orally in the following order:
* Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
* Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
* Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
|
T80-H12.5 / T80-A5-H12.5 / T80-A5
n=6 Participants
Participants received the three treatments, the treatments were administered orally in the following order:
* Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5)
* Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination tablet (T80-A5-H12.5)
* Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5)
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
29.0 Years
STANDARD_DEVIATION 4.9 • n=5 Participants
|
27.3 Years
STANDARD_DEVIATION 5.2 • n=7 Participants
|
27.0 Years
STANDARD_DEVIATION 4.2 • n=5 Participants
|
25.8 Years
STANDARD_DEVIATION 4.1 • n=4 Participants
|
29.5 Years
STANDARD_DEVIATION 5.1 • n=21 Participants
|
29.3 Years
STANDARD_DEVIATION 4.9 • n=8 Participants
|
28.0 Years
STANDARD_DEVIATION 4.6 • n=8 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
36 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 15 minutes (min) before drug administration and 15min, 30min, 45min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h and 72h after 10 days drug administrationPopulation: Pharmacokinetic (PK) set which included all subjects in the treated set who had evaluable PK variable of test (T80/A5/H12.5 mg) and at least one of two references (T80/H12.5 mg and T80/A5 mg) for treatment periods 1, 2, and 3. Subjects who had a protocol deviation relevant to the evaluation of relative bioavailability were excluded.
Maximum measured concentration (Cmax) of telmisartan in plasma at steady state over the dosing interval tau
Outcome measures
| Measure |
T80-A5-H12.5
n=36 Participants
Participants received oral administration of Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination (FDC) tablet (T80-A5-H12.5) once daily for ten days.
|
T80-A5
n=34 Participants
Participants received oral administration of Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5) once daily for 10 days
|
T80-H12.5
n=36 Participants
Participants received oral administration Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5) once daily for 10 days
|
|---|---|---|---|
|
Maximum Measured Concentration (Cmax) at Steady State for Telmisartan
|
970 ng/mL
Geometric Coefficient of Variation 69.3
|
857 ng/mL
Geometric Coefficient of Variation 70.7
|
895 ng/mL
Geometric Coefficient of Variation 75.0
|
PRIMARY outcome
Timeframe: 15 minutes (min) before drug administration and 15min, 30min, 45min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h and 72h after 10 days drug administrationPopulation: PK set
Area under the plasma concentration curve (AUC) of telmisartan in plasma at steady state over the dosing interval tau
Outcome measures
| Measure |
T80-A5-H12.5
n=36 Participants
Participants received oral administration of Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination (FDC) tablet (T80-A5-H12.5) once daily for ten days.
|
T80-A5
n=34 Participants
Participants received oral administration of Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5) once daily for 10 days
|
T80-H12.5
n=36 Participants
Participants received oral administration Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5) once daily for 10 days
|
|---|---|---|---|
|
Area Under the Plasma Concentration Curve at Steady State for Telmisartan
|
2510 ng*h/mL
Geometric Coefficient of Variation 72.1
|
2570 ng*h/mL
Geometric Coefficient of Variation 70.8
|
2580 ng*h/mL
Geometric Coefficient of Variation 81.4
|
PRIMARY outcome
Timeframe: 15 minutes (min) before drug administration and 15min, 30min, 45min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h, 72h, 96h, 120h and 144h after 10 days drug administrationPopulation: PK set
Maximum measured concentration (Cmax) of amlodipine in plasma at steady state over the dosing interval tau
Outcome measures
| Measure |
T80-A5-H12.5
n=36 Participants
Participants received oral administration of Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination (FDC) tablet (T80-A5-H12.5) once daily for ten days.
|
T80-A5
n=34 Participants
Participants received oral administration of Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5) once daily for 10 days
|
T80-H12.5
Participants received oral administration Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5) once daily for 10 days
|
|---|---|---|---|
|
Maximum Measured Concentration (Cmax) at Steady State for Amlodipine
|
11.8 ng/mL
Geometric Coefficient of Variation 21.8
|
11.3 ng/mL
Geometric Coefficient of Variation 22.3
|
—
|
PRIMARY outcome
Timeframe: 15 minutes (min) before drug administration and 15min, 30min, 45min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h, 72h, 96h, 120h and 144h after 10 days drug administrationPopulation: PK set
Area under the plasma concentration curve (AUC) of amlodipine in plasma at steady state over the dosing interval tau
Outcome measures
| Measure |
T80-A5-H12.5
n=36 Participants
Participants received oral administration of Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination (FDC) tablet (T80-A5-H12.5) once daily for ten days.
|
T80-A5
n=34 Participants
Participants received oral administration of Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5) once daily for 10 days
|
T80-H12.5
Participants received oral administration Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5) once daily for 10 days
|
|---|---|---|---|
|
Area Under the Plasma Concentration Curve at Steady State for Amlodipine
|
230 ng*h/mL
Geometric Coefficient of Variation 23.4
|
223 ng*h/mL
Geometric Coefficient of Variation 21.8
|
—
|
PRIMARY outcome
Timeframe: 15 minutes (min) before drug administration and 15min, 30min, 45min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 12h, 24h, 32h and 48h after 10 days drug administrationPopulation: PK set
Maximum measured concentration (Cmax) of HCTZ in plasma at steady state over the dosing interval tau
Outcome measures
| Measure |
T80-A5-H12.5
n=36 Participants
Participants received oral administration of Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination (FDC) tablet (T80-A5-H12.5) once daily for ten days.
|
T80-A5
n=36 Participants
Participants received oral administration of Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5) once daily for 10 days
|
T80-H12.5
Participants received oral administration Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5) once daily for 10 days
|
|---|---|---|---|
|
Maximum Measured Concentration (Cmax) at Steady State for HCTZ
|
107 ng/mL
Geometric Coefficient of Variation 28.5
|
102 ng/mL
Geometric Coefficient of Variation 28.0
|
—
|
PRIMARY outcome
Timeframe: 15 minutes (min) before drug administration and 15min, 30min, 45min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 12h, 24h, 32h and 48h after 10 days drug administrationPopulation: PK set
Area under the plasma concentration curve (AUC) of HCTZ in plasma at steady state over the dosing interval tau
Outcome measures
| Measure |
T80-A5-H12.5
n=36 Participants
Participants received oral administration of Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination (FDC) tablet (T80-A5-H12.5) once daily for ten days.
|
T80-A5
n=36 Participants
Participants received oral administration of Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5) once daily for 10 days
|
T80-H12.5
Participants received oral administration Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5) once daily for 10 days
|
|---|---|---|---|
|
Area Under the Plasma Concentration Curve at Steady State for HCTZ
|
584 ng*h/mL
Geometric Coefficient of Variation 23.8
|
565 ng*h/mL
Geometric Coefficient of Variation 23.4
|
—
|
SECONDARY outcome
Timeframe: 0-6 hours (h), 6-12h and 12-24h after drug administration on day 10Population: PK set
Amount of HCTZ excreted in urine over the time interval from 0 to 24 hours at steady state
Outcome measures
| Measure |
T80-A5-H12.5
n=36 Participants
Participants received oral administration of Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination (FDC) tablet (T80-A5-H12.5) once daily for ten days.
|
T80-A5
n=36 Participants
Participants received oral administration of Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5) once daily for 10 days
|
T80-H12.5
Participants received oral administration Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5) once daily for 10 days
|
|---|---|---|---|
|
Amount of HCTZ Excreted in Urine at Steady State From 0 to 24 Hours
|
10.4 mg
Geometric Coefficient of Variation 11.4
|
9.9 mg
Geometric Coefficient of Variation 12.2
|
—
|
Adverse Events
T80-A5-H12.5
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
T80-H12.5
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
T80-A5
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
All Patients
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
T80-A5-H12.5
n=36 participants at risk
Participants received oral administration of Telmisartan 80mg/Amlodipine 5mg/HCTZ 12.5mg fixed-dose combination (FDC) tablet (T80-A5-H12.5) once daily for ten days.
|
T80-H12.5
n=36 participants at risk
Participants received oral administration Telmisartan 80mg/HCTZ 12.5mg fixed-dose combination tablet (T80-H12.5) once daily for 10 days
|
T80-A5
n=34 participants at risk
Participants received oral administration of Telmisartan 80mg/Amlodipine 5mg fixed-dose combination tablet (T80-A5) once daily for 10 days
|
All Patients
n=36 participants at risk
All participants in the study. Participants received three treatments in a randomised order
* T80-A5-H12.5
* T80-A5
* T80-H12.5
|
|---|---|---|---|---|
|
Investigations
Alanine aminotransferase increased
|
8.3%
3/36 • 10 days
|
5.6%
2/36 • 10 days
|
5.9%
2/34 • 10 days
|
11.1%
4/36 • 10 days
|
|
Investigations
C-reactive protein increased
|
2.8%
1/36 • 10 days
|
2.8%
1/36 • 10 days
|
0.00%
0/34 • 10 days
|
5.6%
2/36 • 10 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