Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study is to compare the rate and extent of absorption of amlodipine from a test formulation of Amlodipine Besylate Tablets, 10 mg versus the reference Norvasc® 10 mg Tablets under fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
10 mg Tablet
DRUGNorvasc®
10 mg Tablet
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
* Non-smoking male or female with a minimum age of 18 years (i.e. non-smoker or non-tobacco user for at least 90 days prior to pre-study medical screening). * Body Mass Index (BMI = weight/height2) greater than or equal to 19.0 kg.m2 and less than or equal to 30.0 kg/m2. * Normal findings in the physical examination, 12-lead ECG and vital signs (blood pressure between 106-140/66-90 mmHg, heart rate between 55-99 beats/min). * Negative for drugs of abuse, nicotine, hepatitis B-surface antigen, hepatitis C and HIV, and for female subjects, pregnancy (serum β-CG). * No clinical laboratory values outside of the acceptable range as defined by BCR, unless the Principal Investigator decides they are not clinically significant. * Female subjects who are surgically sterile for at least six months or post-menopausal for at least one year, or who will avoid pregnancy prior to the study, during the study and up until one month after the end of the study.
Exclusion criteria
* Known history of hypersensitivity to amlodipine (e.g. Norvasc®) and/or related drugs such as nifedipine, diltiazem HCl, verapamil or felodipine. * Known history or presence of cardiac, pulmonary, gastrointestinal, endocrine, musculoskeletal, neurological, hematological, liver or kidney disease, unless judged not clinically significant by the Principal Investigator or medical designate. * Known history or presence of food allergies, or any condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs. * Any clinically significant illness during the last four weeks prior to entry into this study. * Presence of any significant physical or organ abnormality. * Any subject with a history of drug abuse. * Any history or evidence of psychiatric or psychological disease (including depression) unless deemed not clinically significant by the Principal Investigator, or medical designate. * Use of any prescription medication within 14 days preceding entry into this study. * Use of over the counter (OTC) medication within seven days preceding entry into this study (except for spermicidal/barrier contraceptive products). * Female subjects: use of contraceptives (oral, transdermal, implant, Mirena® IUD) within 30 days prior to drug administration or a depot injection of progestogen drug (e.g. Depo-Provera®) within one year prior to drug administration. * Female subjects: presence of pregnancy or lactation. * Any subject who has had blood drawn within 56 days preceding this study, taken during the conduct of any clinical study at a facility other than BCR, or within the lockout period specified by a previous study conducted at BCR. * Participation in a clinical trial with an investigational drug within 30 days preceding this study. * Any subject who has donated blood within 56 days preceding this study. * Any subject who has participated as a plasma donor in a plasmapheresis program within seven days preceding this study. * Significant or recent history of asthma (after 12 years of age). * Any subject with a recent (less than one year) history of alcohol abuse. * Known history of frequent headaches or migraines. * Intolerance to venipuncture.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration | Blood samples collected over 168 hour period | Bioequivalence based on Cmax |
| AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | Blood samples collected over 168 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 168 hour period | Bioequivalence based on AUC0-t |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Amlodipine Besylate (Test) First Amlodipine Besylate 10 mg tablet (test) dosed in first period followed by Norvasc® 10 mg tablet (reference)dosed in second period | 14 |
| Norvasc® (Reference) First Norvasc® 10 mg tablet (reference) dosed in first period followed by Amlodipine Besylate 10 mg tablet (test) dosed in second period | 14 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Amlodipine Besylate (Test) First | Norvasc® (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 | 14 Participants | 14 Participants | 28 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 11 Participants | 13 Participants | 24 Participants |
| Race/Ethnicity, Customized Mulatto | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Canada | 14 participants | 14 participants | 28 participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 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 168 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 323.27 ng*h/mL | Standard Deviation 106.34 |
| Norvasc® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 326.49 ng*h/mL | Standard Deviation 107.4 |
90% CI: [93.38, 104.66]
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 168 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 299.84 ng*h/mL | Standard Deviation 90.8 |
| Norvasc® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 302.52 ng*h/mL | Standard Deviation 95.13 |
90% CI: [93.87, 104.88]
Primary
Cmax - Maximum Observed Concentration
Bioequivalence based on Cmax
Time frame: Blood samples collected over 168 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine | Cmax - Maximum Observed Concentration | 6.16 ng/mL | Standard Deviation 1.64 |
| Norvasc® | Cmax - Maximum Observed Concentration | 6.29 ng/mL | Standard Deviation 1.81 |
90% CI: [94.2, 102.34]