Telmisartan and Amlodipine Versus Monocomponent Tablets

Study Overview
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Brief Summary
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This study will be an open-label, randomized, two-treatment, two-period, two-sequence crossover study to evaluate the bioequivalence of the amlodipine component of Boehringer Ingelheim Pharma GmbH & Co. KGs 80 mg telmisartan/10 mg amlodipine fixed dose combination tablet to the corresponding mono-component amlodipine tablets, 10 mg (Pfizers Norvasc).

Official Title
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A Single-Dose, Comparative Bioavailability Study of Telmisartan/Amlodipine 80 mg/10 mg Tablets Versus Micardis 80 mg Tablets With Norvasc 10 mg Tablets Under Fasting Conditions

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Telmisartan/Amlodipine Combination Tablet
* Drug: Amlodipine Monocomponent


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy, non-smoking, male and/or post-menopausal/surgically sterile female subjects from 18 to 55 years of age. Females who participate in this study must either: be post-menopausal for at least 1 year (no menstrual cycle for 12 consecutive months) and deemed post-menopausal by a physician based on screening clinical laboratory tests (Follicle stimulating hormone (FSH) and Luteinising Hormone (LH) provide proof of surgical sterility. Body Mass Index (BMI) greater than or equal to 19.0 and less than or equal to 30.0 kg/m2. No clinically significant findings in vital signs measurements and systolic blood pressure greater than or equal to 110 mmHg at screening. No clinically significant abnormal laboratory values. No clinically significant findings in a 12-lead electrocardiogram (ECG) and the time between the P and the R waves on the ECG (PR interval) less than or equal to 200 ms at screening. Have no significant diseases. Be informed of the nature of the study and give written consent prior to receiving any study procedure. Have no clinically significant findings from a physical examination. Exclusion criteria: Known history or presence of any clinically significant medical condition. Known or suspected carcinoma. History or presence of cardiovascular dysfunction (e.g. increased angina, myocardial infarction, outflow obstruction, congestive heart failure). History of clinically significant hypotension. Presence of hepatic dysfunction. Known history or presence of galactose or fructose intolerance, sucrase-isomaltase insufficiency, Lapp lactase insufficiency, galactosemia, or glucose-galactose malabsorption syndrome. History of gastrointestinal tract surgery (appendectomy is permitted). Presence of clinically significant gastrointestinal disease or history of malabsorption within the last year. Presence of a medical condition requiring regular medication (prescription and/or over-the-counter) with systemic absorption. History of drug or alcohol addiction requiring treatment. Positive test result for serum hCG consistent with pregnancy (females only), HIV, Hepatitis B surface antigen, or Hepatitis C antibody. Positive test result for urine drugs of abuse (cannabinoids, opiates, amphetamines, cocaine, phencyclidine, tricyclic antidepressants, barbiturates, methadone, and benzodiazepines) or urine cotinine. Difficulty fasting or consuming standard meals. Females who are pregnant, lactating, or likely to become pregnant during the study. Does not tolerate venipuncture. Use of tobacco or nicotine-containing products within 6 months prior to drug administration. On a special diet within 30 days prior to drug administration (e.g. liquid, protein, raw food diet). Participated in another clinical trial or received an investigational product within 30 days prior to drug administration. Donation or loss of whole blood: Great than or equal to 50 mL and less than or equal to 499 mL within 30 days prior to dosing greater than or equal to 500 mL within 56 days prior to dosing. Females who have used hormonal contraceptives within 6 months prior to drug administration. Have had a tattoo or body piercing within 30 days prior to dosing. Known history or presence of hypersensitivity or idiosyncratic reaction to telmisartan, amlodipine, or any other drug substances with similar activity. Use of any drugs known to: induce (e.g. barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole) inhibit (e.g. antidepressants (Selective Seratonin Reuptake Inhibitor (SSRI)I), cimetidine, diltiazem, macrolides, imidazoles, neuroleptics, verapamil, fluoroquinolones, antihistamines) hepatic drug metabolism within 30 days prior to drug administration.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Telmisartan/Amlodipine Fixed Dose<br>Telmisartan/Amlodipine medium fixed dose combination tablet once daily. | Drug: Telmisartan/Amlodipine Combination Tablet<br>* Combination Tablet<br>|
| Active Comparator: Amlodipine Monocomponent<br>Amlodipine Monocomponent 10mg tablet once daily | Drug: Amlodipine Monocomponent<br>* Active Comparator<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 Plasma Amlodipine From 0 to 72 Hours (AUC72) | Area under the analyte concentration versus time curve from time zero to 72 hours as calculated by the linear trapezoidal method | Day 1, Day 22 | 
| Maximum Observed Plasma Concentration (Cmax) of Amlodipine |  | Day 1, Day 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of Maximum Concentration of Amlodipine (TMAX) | Time of maximum measured amlodipine concentration over the zero to 72 hour sampling period | Day 1, Day 22 |