Bioequivalence Study of Telmisartan Between Telmisartan 80 mg/Amlodipine 5 mg FDC Tablet and Telmisartan 80 mg Tab and Amlodipine 5 mg Tab Concomitant Use

• AUC0-tz [ 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 ] [ Designated as safety issue: No ]
  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 [ 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 ] [ Designated as safety issue: No ]
  maximum measured concentration of Telmisartan in plasma

• telmisartan: 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: 4days ] [ Designated as safety issue: No ]
• telmisartan : Cmax (maximum measured concentration of the analyte in plasma) [ Time Frame: 4days ] [ Designated as safety issue: No ]

• AUC0-∞ [ 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 ] [ Designated as safety issue: No ]
  area under the concentration-time curve of Telmisartan in plasma over the time interval from 0 extrapolated to infinity
• Tmax [ 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 ] [ Designated as safety issue: No ]
  time from dosing to the maximum concentration of Telmisartan in plasma
• λz [ 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 ] [ Designated as safety issue: No ]
  terminal rate constant of Telmisartan in plasma
• t1/2 [ 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 ] [ Designated as safety issue: No ]
  terminal half-life of Telmisartan in plasma
• MRTpo [ 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 ] [ Designated as safety issue: No ]
  mean residence time of Telmisartan in the body after oral administration

• telmisartan AUC0-8 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) [ Time Frame: 4days ] [ Designated as safety issue: No ]
• telmisartan : tmax (time from dosing to the maximum concentration of the analyte in plasma) [ Time Frame: 4days ] [ Designated as safety issue: No ]
• telmisartan : t1/2 (terminal half life of the analyte in plasma) [ Time Frame: 4days ] [ Designated as safety issue: No ]

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

Purpose:

• Drug: Telmisartan/Amlodipin FDC
  Telmisartan80mg/Amlodipin5mg FDC
• Drug: Telmisartan
  Telmisartan 80 mg tablet
• Drug: Amlodipin
  Amlodipin 5mg tablet

• Experimental: Telmisartan80mg/Amlodipin5mg FDC
  single-dose, four-period replicated crossover design
  Intervention: Drug: Telmisartan/Amlodipin FDC
• Experimental: Telmisartan80mgtab + Amlodipin5mg tab
  single-dose, four-period replicated crossover design
  Interventions:

  • Drug: Telmisartan
  • Drug: Amlodipin

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