Telmisartan, Amlodipine and Combination in Healthy Subjects

A Single-centre, Randomized, Open-label, Three-period Crossover Pharmacokinetic Study of 80 mg Telmisartan / 5 mg Amlodipine Fixed Dose Combination Compared With Its Monocomponents in Healthy Chinese Subjects

To determine the pharmacokinetic profile of 80 mg telmisartan / 5 mg amlodipine (T80/A5) dose combination after single dose in healthy Chinese subjects.

To determine whether a pharmacokinetic interaction exists between telmisartan and amlodipine, following single doses of 80mg telmisartan (T80), and 5 mg amlodipine (A5) tablet alone and in combination, in healthy Chinese subjects.

To evaluate the safety and tolerability of T80 and A5 alone and in combination in healthy Chinese subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: amlodipine/telmisartan/combination

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • 1235.30.86001 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

1. Healthy males and females
2. Aged between 18 and 45 years
3. Body weight more than 50Kg , and Body Mass Index (BMI ) between 19 and 24 kg/m2

Exclusion criteria

1. Any finding of the medical examination deviating from normal and of clinical relevance
2. Any evidence of a clinically relevant concomitant disease
3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
4. Surgery of the gastrointestinal tract (except appendectomy)
5. Diseases of the central nervous system or psychiatric disorders or neurological disorders
6. History of relevant orthostatic hypotension, fainting spells or blackouts.
7. Chronic or relevant acute infections
8. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
9. Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
10. Use of drugs which might reasonably influence the results of the trial
11. Participation in another trial with an investigational drug within two months prior to administration or during the trial
12. Smoker
13. Inability to refrain from smoking during 24 hours prior to dosing and during the trial
14. Alcohol abuse or inability to stop alcoholic beverages for 24 hours prior to dosing and during the trial
15. Drug abuse
16. Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
17. Excessive physical activities (within one week prior to administration or during the trial)
18. Any laboratory value outside the reference range that is of clinical relevance
19. Inability to comply with dietary regimen of trial site
20. A history of additional risk factors for torsade de pointes
21. Any history of relevant low blood pressure
22. Supine blood pressure at screening of systolic <110 mm Hg and diastolic < 60 mm Hg
23. History of urticaria
24. History of angioneurotic edema 25 Pregnancy / positive pregnancy test, or planning to become pregnant during the study or within 1 month of study completion

26. No adequate contraception during the study and until 1 month of study completion 27. Lactation period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: amlodipine/telmisartan/combination; all patients will be assigned to 6 treatment sequences. cross-over design was adopted to ensure each patient would take amlodipine/telmisartan/combination single dose in randomized order	Drug: amlodipine/telmisartan/combination; patient would take amlodipine(5mg)/telmisartan(80mg)/combination(T80+A5mg) single dose in random order, and each dosage will be separated in 21 days interval.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 (AUC_0-tz)	3 periods of single-dose treatment (8 days of sampling) separated by 21 days wash-outs
Area Under the Plasma Concentration-time Curve From the Time of Dosing to Infinity (AUC_0-∞) of Telmisartan	3 periods of single-dose treatment (8 days of sampling) separated by 21 days wash-outs
The Maximum Observed Plasma Concentration (Cmax) of Telmisartan	3 periods of single-dose treatment (8 days of sampling) separated by 21 days wash-outs
AUC_0-tz of Amlodipine	3 periods of single-dose treatment (8 days of sampling) separated by 21 days wash-outs
AUC_0-∞ of Amlodipine	3 periods of single-dose treatment (8 days of sampling) separated by 21 days wash-outs
Cmax of Amlodipine	3 periods of single-dose treatment (8 days of sampling) separated by 21 days of wash-outs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Attain Cmax (Tmax) of Telmisartan		3 periods of single-dose treatment (8 days of sampling) separated by 21 days wash-outs
Terminal Rate Constant in Plasma (λz) of Telmisartan	reflect the speed of drug elimination in vivo	3 periods of single-dose treatment (8 days of sampling) separated by 21 days wash-outs
Mean Residence Time of Telmisartan in the Body After Oral Administration (MRT_po)		3 periods of single-dose treatment (8 days of sampling) separated by 21 days wash-outs
Elimination Half-life (t_½) of Telmisartan		3 periods of single-dose treatment (8 days of sampling) separated by 21 days wash-outs
Apparent Clearance of Telmisartan in Plasma Following Extravascular Administration (CL/F)		3 periods of single-dose treatment (8 days of sampling) separated by 21 days wash-outs
Apparent Volume of Distribution During the Terminal Phase λz Following an Extravascular Administration (V_z/F) of Telmisartan		3 periods of single-dose treatment (8 days of sampling) separated by 21 days wash-outs
Tmax of Amlodipine		3 periods of single-dose treatment (8 days of sampling) separated by 21 days wash-outs
λz of Amlodipine		3 periods of single-dose treatment (8 days of sampling) separated by 21 days wash-outs
MRT_po of Amlodipine		3 periods of single-dose treatment (8 days of sampling) separated by 21 days wash-outs
t_½ of Amlodipine		3 periods of single-dose treatment (8 days of sampling) separated by 21 days wash-outs
CL/F of Amlodipine		3 periods of single-dose treatment (8 days of sampling) separated by 21 days wash-outs
V_z/F of Amlodipine		3 periods of single-dose treatment (8 days of sampling) separated by 21 days wash-outs
Number of Participants With at Least One Treatment Emergent Adverse Event		4 weeks
Number of Participants With Clinically Relevant Findings in Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities		4 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Synopsis

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: August 10, 2010
• First Submitted That Met QC Criteria: August 12, 2010
• First Posted (Estimate): August 13, 2010

Study Record Updates

• Last Update Posted (Estimate): July 24, 2014
• Last Update Submitted That Met QC Criteria: July 15, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Amlodipine; Telmisartan; Telmisartan amlodipine combination
• Other Study ID Numbers: 1235.30