Healthy
Conditions
Brief summary
The study will be performed as an open-label, randomised, single-dose, two-sequence, four-period replicated crossover design. A total of 72 Japanese healthy male subjects will be randomised to 2 groups. The subjects are administrated either T80/A5/H12.5 mg FDC tablet once or T80/A5 mg FDC tablet and hydrochlorothiazide (HCTZ) 12.5 mg tablet once in each period. The length of admission will be 7 days in each period.
Interventions
DRUGT80/A5 mg FDC tablet
DRUGH12.5 mg tablet
DRUGT80/A5/H12.5 ng FDC tablet
A Telmisartan 80 mg/Amlodipine 5 mg/HCTZ 12.5 mg FDC tablet
DRUGH12.5 mf tablet
A HCTZ 12.5 mg tablet
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects age =20 and =35 years; body weight: =50 kg and =80 kg; body mass index: =18.0 and =25.0 kg/m2 * Without any clinically significant findings and complications on the basis of a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR), body temperature), 12-lead electrocardiograms (ECGs), clinical laboratory tests * Signed and dated written informed consent prior to admission to the trial in accordance with the Good Clinical Practice (GCP) and the local legislation.
Exclusion criteria
\- Any finding of the medical examination (including BP, PR and ECGs) deviating from normal and of clinical relevance.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax for Telmisartan | 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 | Cmax (maximum measured concentration of the analyte in plasma) |
| 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) | 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 | 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) |
| AUC0-tz for Amlodipine | 3hours(h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h, 72h, 96h, 120h, 144h after drug administration | 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) |
| Cmax for Amlodipine | 3hours(h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h, 72h, 96h, 120h, 144h after drug administration | Cmax (maximum measured concentration of the analyte in plasma) |
| Cmax for Hydrochlorothiazide | 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 | Cmax (maximum measured concentration of the analyte in plasma) |
| AUC0-tz for Hydrochlorothiazide | 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 | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-∞ for Telmisartan | 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 | AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |
| AUC0-∞ for Amlodipine | 3hours(h) before drug administration and 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 32h, 48h, 72h, 96h, 120h, 144h after drug administration | AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |
| AUC0-∞ for Hydrochlorothiazide | 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 | AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |
Countries
Japan
Participant flow
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).
Participants by arm
| Arm | Count |
|---|---|
| Sequence TRRT 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. | 36 |
| Sequence RTTR 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. | 36 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 (8 Trial Days) | Withdrawal by Subject | 0 | 1 |
| Period 3 (8 Trial Days) | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Sequence TRRT | Sequence RTTR | Total |
|---|---|---|---|
| Age, Continuous | 26.3 years STANDARD_DEVIATION 4.7 | 27.2 years STANDARD_DEVIATION 5 | 26.7 years STANDARD_DEVIATION 4.8 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 36 Participants | 36 Participants | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 71 | 0 / 72 | 0 / 72 |
| serious Total, serious adverse events | 0 / 71 | 0 / 72 | 0 / 72 |
Outcome results
Primary
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)
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Treatment | 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) | 2850 ng*h/mL | Geometric Coefficient of Variation 52 |
| Reference Treatment | 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) | 2790 ng*h/mL | Geometric Coefficient of Variation 54.9 |
Comparison: The statistical model used for the analysis of AUC0-tz was a mixed effect model on the logarithmic scale.90% CI: [98.94, 105.08]
Primary
AUC0-tz for Amlodipine
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
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Treatment | AUC0-tz for Amlodipine | 171 ng*h/mL | Geometric Coefficient of Variation 24.3 |
| Reference Treatment | AUC0-tz for Amlodipine | 172 ng*h/mL | Geometric Coefficient of Variation 25 |
Comparison: The statistical model used for the analysis of AUC0-tz was a mixed effect model on the logarithmic scale.90% CI: [98.08, 100.94]
Primary
AUC0-tz for Hydrochlorothiazide
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
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Treatment | AUC0-tz for Hydrochlorothiazide | 638 ng*h/mL | Geometric Coefficient of Variation 19.3 |
| Reference Treatment | AUC0-tz for Hydrochlorothiazide | 611 ng*h/mL | Geometric Coefficient of Variation 19.6 |
Comparison: The statistical model used for the analysis of AUC0-tz was a mixed effect model on the logarithmic scale.90% CI: [102.53, 106.1]
Primary
Cmax for Amlodipine
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
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Treatment | Cmax for Amlodipine | 3.69 ng/mL | Geometric Coefficient of Variation 22 |
| Reference Treatment | Cmax for Amlodipine | 3.68 ng/mL | Geometric Coefficient of Variation 20.7 |
Comparison: The statistical model used for the analysis of Cmax was a mixed effect model on the logarithmic scale.90% CI: [98.45, 101.72]
Primary
Cmax for Hydrochlorothiazide
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
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Treatment | Cmax for Hydrochlorothiazide | 104 ng/mL | Geometric Coefficient of Variation 23 |
| Reference Treatment | Cmax for Hydrochlorothiazide | 94.7 ng/mL | Geometric Coefficient of Variation 23.4 |
Comparison: The statistical model used for the analysis of Cmax was a mixed effect model on the logarithmic scale.90% CI: [106.87, 113.54]
Primary
Cmax for Telmisartan
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
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Treatment | Cmax for Telmisartan | 718 ng/mL | Geometric Coefficient of Variation 56.4 |
| Reference Treatment | Cmax for Telmisartan | 694 ng/mL | Geometric Coefficient of Variation 55.2 |
Comparison: The statistical model used for the analysis of Cmax was a mixed effect model on the logarithmic scale.90% CI: [97.03, 110.99]
Secondary
AUC0-∞ for Amlodipine
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
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Treatment | AUC0-∞ for Amlodipine | 184 ng*h/mL | Geometric Coefficient of Variation 25.2 |
| Reference Treatment | AUC0-∞ for Amlodipine | 185 ng*h/mL | Geometric Coefficient of Variation 26 |
Comparison: The statistical model used for the analysis of AUC0--∞ was a mixed effect model on the logarithmic scale.90% CI: [97.94, 100.93]
Secondary
AUC0-∞ for Hydrochlorothiazide
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
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Treatment | AUC0-∞ for Hydrochlorothiazide | 661 ng*h/mL | Geometric Coefficient of Variation 18.7 |
| Reference Treatment | AUC0-∞ for Hydrochlorothiazide | 634 ng*h/mL | Geometric Coefficient of Variation 18.9 |
Comparison: The statistical model used for the analysis of AUC0--∞ was a mixed effect model on the logarithmic scale.90% CI: [102.68, 106.1]
Secondary
AUC0-∞ for Telmisartan
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
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Treatment | AUC0-∞ for Telmisartan | 3090 ng*h/mL | Geometric Coefficient of Variation 54.5 |
| Reference Treatment | AUC0-∞ for Telmisartan | 3120 ng*h/mL | Geometric Coefficient of Variation 58.8 |
Comparison: The statistical model used for the analysis of AUC0--∞ was a mixed effect model on the logarithmic scale.90% CI: [96.8, 103.8]