Telmisartan, Amlodipine and Combination in Healthy Subjects

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: amlodipine/telmisartan/combination


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Healthy males and females Aged between 18 and 45 years Body weight more than 50Kg , and Body Mass Index (BMI ) between 19 and 24 kg/m2 Exclusion criteria Any finding of the medical examination deviating from normal and of clinical relevance Any evidence of a clinically relevant concomitant disease Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Surgery of the gastrointestinal tract (except appendectomy) Diseases of the central nervous system or psychiatric disorders or neurological disorders History of relevant orthostatic hypotension, fainting spells or blackouts. Chronic or relevant acute infections History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) 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 Use of drugs which might reasonably influence the results of the trial Participation in another trial with an investigational drug within two months prior to administration or during the trial Smoker Inability to refrain from smoking during 24 hours prior to dosing and during the trial Alcohol abuse or inability to stop alcoholic beverages for 24 hours prior to dosing and during the trial Drug abuse Blood donation (more than 100 mL within four weeks prior to administration or during the trial) Excessive physical activities (within one week prior to administration or during the trial) Any laboratory value outside the reference range that is of clinical relevance Inability to comply with dietary regimen of trial site A history of additional risk factors for torsade de pointes Any history of relevant low blood pressure Supine blood pressure at screening of systolic <110 mm Hg and diastolic < 60 mm Hg History of urticaria 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: amlodipine/telmisartan/combination<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |