Hypertension
Conditions
Brief summary
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).
Interventions
DRUGTelmisartan/Amlodipine Combination Tablet
Combination Tablet
DRUGAmlodipine Monocomponent
Active Comparator
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy, non-smoking, male and/or post-menopausal/surgically sterile female subjects from 18 to 55 years of age. 2. Females who participate in this study must either: 1. 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) 2. provide proof of surgical sterility. 3. Body Mass Index (BMI) greater than or equal to 19.0 and less than or equal to 30.0 kg/m2. 4. No clinically significant findings in vital signs measurements and systolic blood pressure greater than or equal to 110 mmHg at screening. 5. No clinically significant abnormal laboratory values. 6. 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. 7. Have no significant diseases. 8. Be informed of the nature of the study and give written consent prior to receiving any study procedure. 9. Have no clinically significant findings from a physical examination.
Exclusion criteria
1. Known history or presence of any clinically significant medical condition. 2. Known or suspected carcinoma. 3. History or presence of cardiovascular dysfunction (e.g. increased angina, myocardial infarction, outflow obstruction, congestive heart failure). 4. History of clinically significant hypotension. 5. Presence of hepatic dysfunction. 6. Known history or presence of galactose or fructose intolerance, sucrase-isomaltase insufficiency, Lapp lactase insufficiency, galactosemia, or glucose-galactose malabsorption syndrome. 7. History of gastrointestinal tract surgery (appendectomy is permitted). 8. Presence of clinically significant gastrointestinal disease or history of malabsorption within the last year. 9. Presence of a medical condition requiring regular medication (prescription and/or over-the-counter) with systemic absorption. 10. History of drug or alcohol addiction requiring treatment. 11. Positive test result for serum hCG consistent with pregnancy (females only), HIV, Hepatitis B surface antigen, or Hepatitis C antibody. 12. Positive test result for urine drugs of abuse (cannabinoids, opiates, amphetamines, cocaine, phencyclidine, tricyclic antidepressants, barbiturates, methadone, and benzodiazepines) or urine cotinine. 13. Difficulty fasting or consuming standard meals. 14. Females who are pregnant, lactating, or likely to become pregnant during the study. 15. Does not tolerate venipuncture. 16. Use of tobacco or nicotine-containing products within 6 months prior to drug administration. 17. On a special diet within 30 days prior to drug administration (e.g. liquid, protein, raw food diet). 18. Participated in another clinical trial or received an investigational product within 30 days prior to drug administration. 19. Donation or loss of whole blood: 1. Great than or equal to 50 mL and less than or equal to 499 mL within 30 days prior to dosing 2. greater than or equal to 500 mL within 56 days prior to dosing. 20. Females who have used hormonal contraceptives within 6 months prior to drug administration. 21. Have had a tattoo or body piercing within 30 days prior to dosing. 22. Known history or presence of hypersensitivity or idiosyncratic reaction to telmisartan, amlodipine, or any other drug substances with similar activity. 23. Use of any drugs known to: 1. induce (e.g. barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole) 2. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of Plasma Amlodipine From 0 to 72 Hours (AUC72) | Day 1, Day 22 | Area under the analyte concentration versus time curve from time zero to 72 hours as calculated by the linear trapezoidal method |
| Maximum Observed Plasma Concentration (Cmax) of Amlodipine | Day 1, Day 22 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of Maximum Concentration of Amlodipine (TMAX) | Day 1, Day 22 | Time of maximum measured amlodipine concentration over the zero to 72 hour sampling period |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes all subjects randomized to either treatment sequence | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 0 | 1 |
| Period 1 | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 39 years STANDARD_DEVIATION 9 |
| Body Mass Index | 26.7 kilogram / square meter STANDARD_DEVIATION 2.5 |
| Height | 173.1 centimeter STANDARD_DEVIATION 7.1 |
| Race/Ethnicity, Customized Asian | 3 participants |
| Race/Ethnicity, Customized Black/African American | 6 participants |
| Race/Ethnicity, Customized Hispanic/Latino | 7 participants |
| Race/Ethnicity, Customized White | 12 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 27 Participants |
| Weight | 80.3 kilogram STANDARD_DEVIATION 9.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 27 | 3 / 27 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 |
Outcome results
Primary
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
Time frame: Day 1, Day 22
Population: Analysis Set includes all randomized participants who completed the trial
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telm/Amlo 80 mg/10 mg | Area Under the Concentration-time Curve of Plasma Amlodipine From 0 to 72 Hours (AUC72) | 260.7971 nanograms*hour/milliliter | Standard Deviation 60.8717 |
| Telm 80 mg + Amlo 10 mg | Area Under the Concentration-time Curve of Plasma Amlodipine From 0 to 72 Hours (AUC72) | 276.6315 nanograms*hour/milliliter | Standard Deviation 66.1935 |
Comparison: Telmisartan/Amlodipine 80 mg/10 mg versus Telmisartan 80 mg + Amlodipine 10 mg The two formulations are shown to be bioequivalent since the 90% confidence interval of the test to reference ratio is entirely contained within the 80-125% bioequivalence range.p-value: 0.00590% CI: [91.6, 97.51]ANOVA
Primary
Maximum Observed Plasma Concentration (Cmax) of Amlodipine
Time frame: Day 1, Day 22
Population: Analysis Set includes all randomized participants who completed the trial
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telm/Amlo 80 mg/10 mg | Maximum Observed Plasma Concentration (Cmax) of Amlodipine | 6.7465 nanograms/milliliter | Standard Deviation 1.3354 |
| Telm 80 mg + Amlo 10 mg | Maximum Observed Plasma Concentration (Cmax) of Amlodipine | 7.2258 nanograms/milliliter | Standard Deviation 1.6549 |
Comparison: Telmisartan/Amlodipine 80 mg/10 mg versus Telmisartan 80 mg + Amlodipine 10 mg The two formulations are shown to be bioequivalent since the 90% confidence interval of the test to reference ratio is entirely contained within the 80-125% bioequivalence range.p-value: 0.009390% CI: [90.7, 97.63]ANOVA
Secondary
Time of Maximum Concentration of Amlodipine (TMAX)
Time of maximum measured amlodipine concentration over the zero to 72 hour sampling period
Time frame: Day 1, Day 22
Population: Analysis Set includes all randomized participants who completed the trial
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telm/Amlo 80 mg/10 mg | Time of Maximum Concentration of Amlodipine (TMAX) | 6.69 hours | Standard Deviation 1.95 |
| Telm 80 mg + Amlo 10 mg | Time of Maximum Concentration of Amlodipine (TMAX) | 6.12 hours | Standard Deviation 1.4 |
Comparison: Telmisartan/Amlodipine 80 mg/10 mg versus Telmisartan 80 mg + Amlodipine 10 mgp-value: 0.153ANOVA