Healthy
Conditions
Brief summary
To investigate the bioequivalence of telmisartan administrated in two different ways: both in telmisartan 80 mg/amlodipine 5 mg fixed-dose combination tablets (T) and as telmisartan 80 mg tablet and amlodipine 5 mg tablets (R) in concomitant use
Detailed description
Purpose:
Interventions
DRUGTelmisartan/Amlodipin FDC
Telmisartan80mg/Amlodipin5mg FDC
DRUGTelmisartan
Telmisartan 80 mg tablet
DRUGAmlodipin
Amlodipin 5mg tablet
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
1. Without any clinically significant findings and complications on the basis of a complete medical history, including the physical examination, vital signs (blood pressure, pulse rate, body temperature), 12-lead electrocardiograms (ECGs), clinical laboratory tests 2. Age: =20 and =35 years 3. Body weight: =50 kg and =80 kg 4. Body mass index (BMI): =18.0 and =25.0 kg/m2
Exclusion criteria
1. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, or hormonal disorders 2. Diseases of the central nervous system (such as epilepsy) or psychiatric or neurological disorders 3. Chronic or relevant acute infections 4. Any clinical relevant findings in laboratory test results deviating from normal 5. A positive result in hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibodies, a syphilis test, or an human immunodeficiency virus (HIV) test 6. History of surgery of the gastrointestinal tract (except appendectomy) 7. History of relevant orthostatic hypotension, fainting spells, or blackouts 8. Known hypersensitivity to any component of the formulation (telmisartan and amlodipine), to any other angiotensin receptor blocker, or to any other dihydropyridine calcium channel blocker compound 9. Intake of drugs with a long half-life (=24 hours) within at least 1 month or less than 10 half-lives of the respective drug before drug administration 10. Intake of drugs which might reasonably influence the results of the trial on the basis of the knowledge at the time of protocol preparation within 7 days before drug administration 11. Participation in another trial with an investigational drug within 1 months or less than 10 times of half-lives of the investigational products before drug administration 12. Smoker (=20 cigarettes/day) 13. Alcohol abuse (60 g or more ethanol/day: e.g., 3 middle-sized bottles of beer, 3 gous \[equivalent to 540 mL\] of sake) 14. Drug abuse 15. Blood donation (more than 100 mL within 4 weeks before drug administration) 16. Excessive physical activities (ex. Marathon etc) within 1 week before drug administration 17. Intake of alcohol within 2 days before drug administration 18. Inability to comply with dietary regimen of the study site 19. Inability to refrain from smoking during trial days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-tz | Serial pharmacokinetic blood samples collected before drug administration, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after drug administration | Area under the concentration-time curve of Telmisartan in plasma over the time interval from 0 to the time of the last quantifiable data point |
| Cmax | Serial pharmacokinetic blood samples collected before drug administration, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after drug administration | maximum measured concentration of Telmisartan in plasma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| λz | Serial pharmacokinetic blood samples collected before drug administration, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after drug administration | terminal rate constant of Telmisartan in plasma |
| AUC0-∞ | Serial pharmacokinetic blood samples collected before drug administration, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after drug administration | area under the concentration-time curve of Telmisartan in plasma over the time interval from 0 extrapolated to infinity |
| MRTpo | Serial pharmacokinetic blood samples collected before drug administration, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after drug administration | mean residence time of Telmisartan in the body after oral administration |
| t1/2 | Serial pharmacokinetic blood samples collected before drug administration, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after drug administration | terminal half-life of Telmisartan in plasma |
| Tmax | Serial pharmacokinetic blood samples collected before drug administration, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after drug administration | time from dosing to the maximum concentration of Telmisartan in plasma |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence A | 32 |
| Treatment Sequence B | 32 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Crossover Period 2 | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Treatment Sequence A | Treatment Sequence B | Total |
|---|---|---|---|
| Age, Continuous | 24.1 Year STANDARD_DEVIATION 3.3 | 24.5 Year STANDARD_DEVIATION 3.8 | 24.3 Year STANDARD_DEVIATION 3.5 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 32 Participants | 32 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 32 | 0 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 |
Outcome results
Primary
AUC0-tz
Area under the concentration-time curve of Telmisartan in plasma over the time interval from 0 to the time of the last quantifiable data point
Time frame: Serial pharmacokinetic blood samples collected before drug administration, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after drug administration
Population: One subject who discontinued the study on period 2 was excluded from Pharmacokinetic data set. Therefore, the number of observed PK parameter were 32+32+31+31=126 in T80/A5 FDC tablet and T80 + A5, respectively.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| T80/A5 mg FDC Tablet | AUC0-tz | 1970 ng*hour/mL | Geometric Coefficient of Variation 67.9 |
| T80mg Tablet and A5 mg Tablet in Concomitant Use | AUC0-tz | 1950 ng*hour/mL | Geometric Coefficient of Variation 67 |
90% CI: [97.7, 104.2]ANOVA
Primary
Cmax
maximum measured concentration of Telmisartan in plasma
Time frame: Serial pharmacokinetic blood samples collected before drug administration, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after drug administration
Population: One subject who discontinued the study on period 2 was excluded from Pharmacokinetic data set. Therefore, the number of observed PK parameter were 32+32+31+31=126 in T80/A5 FDC tablet and T80 + A5, respectively.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| T80/A5 mg FDC Tablet | Cmax | 471 ng/mL | Geometric Coefficient of Variation 88.1 |
| T80mg Tablet and A5 mg Tablet in Concomitant Use | Cmax | 484 ng/mL | Geometric Coefficient of Variation 81.8 |
90% CI: [87.2, 108.3]ANOVA
Secondary
AUC0-∞
area under the concentration-time curve of Telmisartan in plasma over the time interval from 0 extrapolated to infinity
Time frame: Serial pharmacokinetic blood samples collected before drug administration, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after drug administration
Population: One subject who discontinued the study on period 2 was excluded from Pharmacokinetic data set. In analysis only used data which the parameter can be calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| T80/A5 mg FDC Tablet | AUC0-∞ | 2410 ng*hour/mL | Geometric Coefficient of Variation 60.4 |
| T80mg Tablet and A5 mg Tablet in Concomitant Use | AUC0-∞ | 2300 ng*hour/mL | Geometric Coefficient of Variation 62.4 |
90% CI: [98.3, 105.2]ANOVA
Secondary
MRTpo
mean residence time of Telmisartan in the body after oral administration
Time frame: Serial pharmacokinetic blood samples collected before drug administration, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after drug administration
Population: One subject who discontinued the study on period 2 was excluded from Pharmacokinetic data set. In analysis only used data which the parameter can be calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| T80/A5 mg FDC Tablet | MRTpo | 21.8 hour | Geometric Coefficient of Variation 56.2 |
| T80mg Tablet and A5 mg Tablet in Concomitant Use | MRTpo | 19.9 hour | Geometric Coefficient of Variation 50.5 |
90% CI: [101.5, 117.1]ANOVA
Secondary
t1/2
terminal half-life of Telmisartan in plasma
Time frame: Serial pharmacokinetic blood samples collected before drug administration, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after drug administration
Population: One subject who discontinued the study on period 2 was excluded from Pharmacokinetic data set. In analysis only used data which the parameter can be calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| T80/A5 mg FDC Tablet | t1/2 | 23.3 hour | Geometric Coefficient of Variation 52.5 |
| T80mg Tablet and A5 mg Tablet in Concomitant Use | t1/2 | 21.3 hour | Geometric Coefficient of Variation 45.1 |
90% CI: [102.4, 116.8]ANOVA
Secondary
Tmax
time from dosing to the maximum concentration of Telmisartan in plasma
Time frame: Serial pharmacokinetic blood samples collected before drug administration, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after drug administration
Population: One subject who discontinued the study on period 2 was excluded from Pharmacokinetic data set. Therefore, the number of observed PK parameter were 32+32+31+31=126 in T80/A5 FDC tablet and T80 + A5, respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| T80/A5 mg FDC Tablet | Tmax | 0.750 hour | Full Range 0.5 |
| T80mg Tablet and A5 mg Tablet in Concomitant Use | Tmax | 0.750 hour | Full Range 0.25 |
90% CI: [95.8, 124.4]ANOVA
Secondary
λz
terminal rate constant of Telmisartan in plasma
Time frame: Serial pharmacokinetic blood samples collected before drug administration, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after drug administration
Population: One subject who discontinued the study on period 2 was excluded from Pharmacokinetic data set. In analysis only used data which the parameter can be calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| T80/A5 mg FDC Tablet | λz | 0.0297 /hour | Geometric Coefficient of Variation 52.5 |
| T80mg Tablet and A5 mg Tablet in Concomitant Use | λz | 0.0326 /hour | Geometric Coefficient of Variation 45.1 |
90% CI: [85.6, 97.6]ANOVA