Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
This study will compare the relative bioavailability (rate and extent of absorption) of 500 mg Clarithromycin Tablets with that of 500 mg BIAXIN® Tablets following a single oral dose (1 x 500 mg tablet) in healthy adult subjects under fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
DRUGClarithromycin
500 mg Tablet
DRUGBiaxin®
500 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
All subjects selected for this study will be healthy men or women 18 years of age or older at the time of dosing. The subject's body mass index (BMI) should be less than or equal to 30. Each subject will complete the screening process within 28 days prior to period I dosing. Consent documents for both the screening evaluation and HIV antibody determination will be reviewed, discussed and signed by each potential participant before full implementation of screening procedures. Screening will include general observations, physical examination, demographics, medical and medication history, an electrocardiogram, sitting blood pressure and heart rate, respiratory rate and temperature. The physical examination will include, but may not be limited to, an evaluation of the cardiovascular, gastrointestinal, respiratory and central nervous systems. The screening clinical laboratory procedures will include: * HEMATOLOGY: hematocrit, hemoglobin, WBC count with differential, RBC count, platelet count * CLINICAL CHEMISTRY: serum creatinine, BUN, glucose, AST(GOT), ALT(GPT), albumin, total bilirubin, total protein, and alkaline phosphatase * HIV antibody, hepatitis B surface antigen, hepatitis C antibody screens * URINALYSIS: by dipstick; full microscopic examination if dipstick positive * URINE DRUG SCREEN: ethyl alcohol, amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine metabolites, opiates and phencyclidine * SERUM PREGNANCY SCREEN (female subjects only) * FOLLICLE STIMULATING HORMONE (FSH; female subjects only): verify postmenopausal status If female and : is postmenopausal for at least 1 year; or is surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy).
Exclusion criteria
Subjects with a recent history of drug or alcohol addiction or abuse. Subjects with the presence of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or neurologic system(s) or psychiatric disease (as determined by the clinical investigators). Subjects whose clinical laboratory test values are outside the accepted reference range and when confirmed on re-examination are deemed to be clinically significant. Subjects demonstration a positive hepatitis B surface antigen screen, hepatitis C antibody screen or a reactive HIV antibody screen. Subjects demonstrating a positive drug abuse screen when screened for this study. Female subjects who are currently breast feeding. Female subjects who are demonstrating a positive pregnancy screen. Subjects with a history of allergic response(s) to Clarithromycin or related drugs. Subjects with a history of clinically significant allergies including drug allergies. Subjects with a clinically significant illness during the 4 weeks prior to Period I dosing (as determined by the clinical investigators). Subjects who currently use or reports using tobacco or nicotine-containing products within 90 days prior to Period I dosing. Subjects who have taken any drug known to induce or inhibit hepatic drug metabolism in the 30 days prior to Period I dosing. Subjects who report donating greater than 150 mL of blood within 30 days prior to Period I dosing. All subjects will by advised not to donate blood for four weeks after completing the study. Subjects who have donated plasma (e.g. plasmapheresis) within 14 days prior to Period I dosing. All subjects will be advised not to donate plasma for four weeks after completing the study. Subjects who report receiving any investigational drug within 30 days prior to Period I dosing. Subjects who report taking any prescription medication in the 14 days prior to Period I dosing, with the exception of topical products without systemic absorption. Subjects who have been on an abnormal diet during the 28 days prior to Period I dosing. Subjects who report an intolerance of direct venipuncture.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration | Blood samples collected over 48 hour period | Bioequivalence based on Cmax |
| AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | Blood samples collected over 48 hour period | Bioequivalence based on AUC0-t |
| AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | Blood samples collected over 48 hour period | Bioequivalence based on AUC0-t |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Clarithromycin (Test) First Clarithromycin 500 mg Tablet (test) dosed in first period followed by Biaxin® 500 mg Tablet (reference) dosed in second period | 28 |
| Biaxin® (Reference) First Biaxin® 500 mg Tablet (reference) dosed in first period followed by Clarithromycin 500 mg Tablet dosed in second period | 28 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Clarithromycin (Test) First | Biaxin® (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 | 28 Participants | 28 Participants | 56 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 27 Participants | 23 Participants | 50 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment United States | 28 participants | 28 participants | 56 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 26 Participants | 26 Participants | 52 Participants |
Outcome results
Primary
AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)
Bioequivalence based on AUC0-t
Time frame: Blood samples collected over 48 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clarithromycin | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 17380.442 ng*h/mL | Standard Deviation 6167.362 |
| Biaxin® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 18481.089 ng*h/mL | Standard Deviation 5728.638 |
90% CI: [89.6, 97.6]
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 48 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clarithromycin | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 17265.639 ng*h/mL | Standard Deviation 6136.361 |
| Biaxin® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 18362.380 ng*h/mL | Standard Deviation 5719.467 |
90% CI: [89.5, 97.7]
Primary
Cmax - Maximum Observed Concentration
Bioequivalence based on Cmax
Time frame: Blood samples collected over 48 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clarithromycin | Cmax - Maximum Observed Concentration | 2170.964 ng/mL | Standard Deviation 690.215 |
| Biaxin® | Cmax - Maximum Observed Concentration | 2214.636 ng/mL | Standard Deviation 763.844 |
90% CI: [91.5, 106]