Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study is to compare the relative bioavailability of cefprozil for oral suspension 250 mg/5 mL (TEVA Pharmaceuticals USA) with that of CEFZIL® for Oral Suspension 250 mg/5 mL (Bristol-Myers Squibb) in healthy, non-smoking adults under non-fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
1 x 250 mg/5 mL, single-dose fasting
1 x 250 mg/5 mL, single-dose fasting
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
* All subjects selected for this study will be non-smokers at least 18 years of age. Subjects will have a BMI (body mass index) of 30 or less. * Each subject shall be given a general physical examination within 28 days of initiation of the study. Such examination includes, but is not limited to, blood pressure, general observations, and history. * Each female subject will be given a serum pregnancy test as part of the pre-study screening process. * Adequate blood and urine samples should be obtained within 28 days before beginning of the first period and at the end of the trial for clinical laboratory measurements. * Clinical laboratory measurements will include the following: 1. Hematology: hemoglobin, hematocrit, red blood cell count, platelets, and white blood cell count (with differential). 2. Clinical Chemistry: creatinine, BUN, glucose, SGOT/AST, SGPT/ALT, bilirubin, and alkaline phosphatase. 3. Urine Analysis: pH, specific gravity, protein, glucose, ketones, bilirubin, occult blood, and cells. 4. HIV Screen: pre-study only. 5. Hepatitis-B, C Screen: pre-study only. 6. Drugs of Abuse Screen: pre-study and at each check-in
Exclusion criteria
* Subjects with a significant recent history of chronic alcohol consumption (past 2 years), drug addiction, or serious gastrointestinal, renal, hepatic or cardiovascular disease, tuberculosis, epilepsy, asthma (past 5 years), diabetes, psychosis or glaucoma will not be eligible for this study. * Subjects whose clinical laboratory test values are outside the reference range may be retested at the discretion of the clinical investigator. If the clinical values are outside the range on retesting, the subject will not be eligible to participate in the study unless the clinical investigator deems the result to not be significant. * Subjects who have a history of allergic responses to the class of drug being tested will be excluded from the study. * Subjects who use tobacco in any form will not be eligible to participate in the study. Three months abstinence is required. * All subjects will have urine samples assayed for the presence of drugs of abuse as part of the clinical laboratory screening procedures and at each dosing period check-in. Subjects found to have urine concentrations of any of the tested drugs will not be allowed to participate. * Subjects should not have donated blood and/or plasma for at least thirty (30) days prior to the first dosing of the study. * Subjects who have taken any investigational drug within thirty (30) days prior to the first dosing of the study will not be allowed to participate. * Female subjects who are pregnant, breast-feeding, or who are likely to become pregnant during the study will not be allowed to participate. Female subjects of child bearing potential must either abstain from sexual intercourse or use a reliable barrier method (e.g. condom, IUD) of contraception during the course of the study (first dosing until last blood collection) or they will not be allowed to participate. Female subjects who have used hormonal oral contraceptives within 14 days of dosing or implanted or injected hormonal contraceptives within 180 days of dosing will not be allowed to participate. * All female subjects will be screened for pregnancy at check-in each study period. Subjects with positive or inconclusive results will be withdrawn from the study. * Subjects who do not tolerate venipuncture will not be allowed to participate.
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
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cefprozil (Test) First 250mg/5mL Cefprozil for Oral Suspension test product dosed in first period followed by 250mg/5mL Cefzil® for Oral Suspension reference product dosed in the second period. | 13 |
| Cefzil® (Reference) First 250mg/5mL Cefzil® for Oral Suspension reference product dosed in first period followed by 250mg/5mL Cefprozil for Oral Suspension test product dosed in the second period. | 13 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Cefprozil (Test) First | Cefzil® (Reference) 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 | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 13 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black | 2 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized White | 24 participants | 11 participants | 13 participants |
| Region of Enrollment United States | 26 participants | 13 participants | 13 participants |
| Sex: Female, Male Female | 13 Participants | 8 Participants | 5 Participants |
| Sex: Female, Male Male | 13 Participants | 5 Participants | 8 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 |
|---|---|---|---|
| Cefprozil (Test) | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | 14.495 ng*h/mL | Standard Deviation 2.204 |
| Cefzil® (Reference) | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | 16.048 ng*h/mL | Standard Deviation 2.72 |
90% CI: [89.1, 92.3]
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 |
|---|---|---|---|
| Cefprozil (Test) | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 14.211 ng*h/mL | Standard Deviation 2.15 |
| Cefzil® (Reference) | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 15.776 ng*h/mL | Standard Deviation 2.702 |
90% CI: [88.9, 92.1]
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 |
|---|---|---|---|
| Cefprozil (Test) | Cmax (Maximum Observed Concentration) | 4.367 ng/mL | Standard Deviation 0.711 |
| Cefzil® (Reference) | Cmax (Maximum Observed Concentration) | 4.915 ng/mL | Standard Deviation 0.859 |
90% CI: [86.2, 92.2]