Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study is to evaluate the comparative bioavailability between trandolapril 4 mg tablets (test) and Mavik® 4 mg Tablets (reference) after a single-dose in healthy subjects under fed conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
1 x 4 mg, single-dose fed
1 x 4 mg, single-dose fed
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy, non-smoking, male and female subjects, 18 years of age or older. * BMI greater than or equal to 19 and less than or equal to 30. * Negative for HIV, Hepatitis B surface antigen and Hepatitis C antibody, urine drugs of abuse test (marijuana, amphetamines, barbiturates, cocaine, opiates, benzodiazepines and methadone), urine cotinine test, serum HCG consistent with pregnancy (females only). * No significant diseases or clinically significant findings in a physical examination. * No clinically significant abnormal laboratory values. * No clinically significant findings in the 12-lead electrocardiogram (ECG). * Blood pressure over 90/60 mmHg and less than 140/90 mmHg. * Be informed of the nature of the study and given written consent prior to receiving any study procedure. * Females who are surgically sterile for at least six months or postmenopausal for at least one year, or who will avoid pregnancy prior to the study, during the study and up to one month after the end of the study. * Females who participate in this study are not pregnant and/or non-lactating.
Exclusion criteria
* Known history or presence of any clinically significant medical condition. * Known history of food allergies, or any condition know to interfere with the absorption, distribution, metabolism or excretion of drugs. * Known or suspected carcinoma. * Presence or history of angioedema. * Known history or presence of hypersensitivity or idiosyncratic reaction to trandolapril and/or any other drug substances with similar activity; alcoholism within the last 12 months; drug dependence and/or substance abuse; use of tobacco or nicotine-containing products, within the last 6 months. * Any clinically significant illness or surgery within 4 weeks prior to drug administration. * On a special diet within 4 weeks 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. * Donated up to 250 mL of blood within the previous 30 days OR donated from 251 to 500 mL of blood in the previous 45 days OR donated more than 500 mL of blood in the previous 56 days (based on the Canadian Blood Services guideline for blood donation). * Use of any prescription medication within 14 days prior to period 1 dosing. Use of any over the counter (OTC) medication within 7 days prior to period 1 dosing (except spermicidal/barrier contraceptive products). * Use of any drug known to induce or inhibit hepatic drug metabolism (examples of inducers: barbiturates, carbamazepine, phenytoine, glucocorticoids, omeprazole; examples of inhibitors: antidepressant (SSRI), cimetidine, diltiazem, macrolides, imidazoles, neuroleptics, verapamil, fluoroquinolones, antihistamines) within 30 days prior to period 1 dosing. * Females taking oral or transdermal hormonal contraceptives within 30 days preceding period 1 dosing OR Females having taken implanted or injected hormonal contraceptives (Depo-Provera) within one year prior to period 1 dosing. * Difficulty fasting or consuming the standard meals. * Do not tolerate venipuncture.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration | Blood samples collected over 72 hour period | Bioequivalence based on Cmax |
| AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | Blood samples collected over 72 hour period | Bioequivalence based on AUC0-inf |
| AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | Blood samples collected over 72 hour period | Bioequivalence based on AUC0-t |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Trandolaprilat | Blood samples collected over 72 hour period | Informational Purposes Only |
| AUC0-72 - Trandolaprilat | Blood samples collected over 72 hour period | Informational Purposes Only |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Trandolapril (Test) First Trandolapril 4 mg Tablet (test) dosed in first period followed by Mavik® 4 mg Tablet (reference) dosed in second period | 25 |
| Mavik® (Reference) First Mavik® 4 mg Tablet (reference) dosed in first period followed by Trandolapril 4 mg Tablet (test) dosed in second period | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Second Intervention | Missed 72 hour blood draw | 1 | 1 |
Baseline characteristics
| Characteristic | Trandolapril (Test) First | Mavik® (Reference) First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 25 Participants | 50 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Black | 6 Participants | 4 Participants | 10 Participants |
| Race/Ethnicity, Customized Caucasian | 17 Participants | 18 Participants | 35 Participants |
| Region of Enrollment Canada | 25 participants | 25 participants | 50 participants |
| Sex: Female, Male Female | 10 Participants | 11 Participants | 21 Participants |
| Sex: Female, Male Male | 15 Participants | 14 Participants | 29 Participants |
Outcome results
Primary
AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)
Bioequivalence based on AUC0-inf
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis. Not all data from completed subjects could be used to determine AUC0-inf.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Trandolapril | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 7.0104 ng*h/mL | Standard Deviation 1.9298 |
| Mavik® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 7.9967 ng*h/mL | Standard Deviation 2.8867 |
90% CI: [96.72, 111.41]
Primary
AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)
Bioequivalence based on AUC0-t
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis. Data from two subjects who did not complete was also included in statistical analysis since the 72 hour blood draw that was missed does not affect the results for Trandolapril.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Trandolapril | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 6.9056 ng*h/mL | Standard Deviation 2.7329 |
| Mavik® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 6.7143 ng*h/mL | Standard Deviation 2.474 |
90% CI: [97.34, 107.65]
Primary
Cmax - Maximum Observed Concentration
Bioequivalence based on Cmax
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis. Data from two subjects who did not complete was also included in statistical analysis since the 72 hour blood draw that was missed does not affect the results for Trandolapril.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Trandolapril | Cmax - Maximum Observed Concentration | 5.2604 ng/mL | Standard Deviation 3.8238 |
| Mavik® | Cmax - Maximum Observed Concentration | 5.4938 ng/mL | Standard Deviation 3.7393 |
90% CI: [85.13, 108.27]
Secondary
AUC0-72 - Trandolaprilat
Informational Purposes Only
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis. Data from two subjects who did not complete was also included in statistical analysis since the 72 hour blood draw that was missed does not affect the results for Trandolapril.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Trandolapril | AUC0-72 - Trandolaprilat | 127.6059 ng*h/mL | Standard Deviation 23.9616 |
| Mavik® | AUC0-72 - Trandolaprilat | 123.4560 ng*h/mL | Standard Deviation 22.6436 |
90% CI: [100.84, 105.92]
Secondary
Cmax - Trandolaprilat
Informational Purposes Only
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis. Data from two subjects who did not complete was also included in statistical analysis since the 72 hour blood draw that was missed does not affect the results for Trandolapril.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Trandolapril | Cmax - Trandolaprilat | 6.9610 ng/mL | Standard Deviation 2.5672 |
| Mavik® | Cmax - Trandolaprilat | 6.6815 ng/mL | Standard Deviation 2.4413 |
90% CI: [100.08, 107.57]