Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study is to compare the relative bioavailability of cefadroxil 500 mg capsules (manufactured by Teva Pharmaceuticals USA) with that of DURICEF® 500 mg capsules (manufactured by Bristol-Myers Squibb Company) when dosed (1 x 500 mg capsules) in normal healthy non-smoking male and female subjects under fed conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
1 x 500 mg
1 x 500 mg
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 19kg/m2 and less than or equal to 30kg/m2. * Availability of subject for the entire study period and willingness to adhere to protocol requirements, as evidenced by a signed Informed Consent Form. * Normal findings in the physical examination, 12-lead ECG and vital signs (blood pressure between 100-140/60-90 mmHg, heart rate between 50-99 beats/min, temperature between 35.8°C and 37.5°C. * 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 the 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 cefadroxil (e.g. Duricel®) and/or related drugs in the family of cephalosporins (Cephalexin, Cefaclor, Cefazolin, Cefuroxime Axetil, Cefotetan, Cefprozil, Cefixime, Ceftriaxone), and/or penicillins (Amoxicillin, Ampicillin, Clozacillin). * Known history or presence of fod 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 andy 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 14 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 or 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, 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 personal history of gastrointestinal illness or disease, particularly colitis. * Any history of severe allergic reaction (including drugs, food, insect bites, environmental allergens). * Intolerance to venipuncture.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax (Maximum Observed Concentration) | Blood samples collected over a 12 hour period. | Bioequivalence based on Cmax. |
| AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | Blood samples collected over a 12 hour period. | Bioequivalence based on AUC0-t. |
| AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | Blood samples collected over a 12 hour period. | Bioequivalence based on AUC0-inf. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cefadroxil (Test) First 500 mg Cefadroxil Capsules test product dosed in first period followed by 500 mg Duricef® Capsules reference product dosed in the second period. | 13 |
| Duricef® (Reference) First 500 mg Duricef® Capsules reference product dosed in first period followed by 500 mg Cefadroxil Capsules test product dosed in the second period. | 13 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout of 7 Days | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Duricef® (Reference) First | Cefadroxil (Test) First |
|---|---|---|---|
| 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 | 26 Participants | 13 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 4 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 9 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 5 participants | 3 participants | 2 participants |
| Race/Ethnicity, Customized Black | 6 participants | 3 participants | 3 participants |
| Race/Ethnicity, Customized White | 15 participants | 7 participants | 8 participants |
| Region of Enrollment United States | 26 participants | 13 participants | 13 participants |
| Sex: Female, Male Female | 13 Participants | 6 Participants | 7 Participants |
| Sex: Female, Male Male | 13 Participants | 7 Participants | 6 Participants |
Outcome results
Primary
AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity)
Bioequivalence based on AUC0-inf.
Time frame: Blood samples collected over a 12 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cefadroxil (Test) | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | 43.987 ng*h/mL | Standard Deviation 7.149 |
| Duricef® (Reference) | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | 44.109 ng*h/mL | Standard Deviation 7.631 |
90% CI: [97.4, 102]
Primary
AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Bioequivalence based on AUC0-t.
Time frame: Blood samples collected over a 12 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cefadroxil (Test) | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 42.656 ng*h/mL | Standard Deviation 7.063 |
| Duricef® (Reference) | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 42.685 ng*h/mL | Standard Deviation 7.572 |
90% CI: [97.5, 103]
Primary
Cmax (Maximum Observed Concentration)
Bioequivalence based on Cmax.
Time frame: Blood samples collected over a 12 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cefadroxil (Test) | Cmax (Maximum Observed Concentration) | 12.024 ng/mL | Standard Deviation 1.405 |
| Duricef® (Reference) | Cmax (Maximum Observed Concentration) | 11.9 ng/mL | Standard Deviation 2.688 |
90% CI: [95.9, 110]