Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The study will compare the relative bioavailability (rate and extent of absorption) of 200 mg/5 mL Azithromycin oral suspension manufactured by TEVA Pharmaceutical Industries Ltd.; distributed by TEVA Pharmaceuticals USA with that of 200 mg/5 mL ZITHROMAX®.
Detailed description
Detailed Description Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods Outcome: Confidence interval fell within 80-125% therefore met the FDA Bioequivalence criteria; no drug related, serious, unexpected adverse events were reported during the study.
Interventions
OTHERAzithromycin
Oral Suspension
DRUGZithromax®
Oral Suspension
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
* Screening Demographics: All subjects selected for this study will be healthy men and women 18 years of age or older at the time of dosing. The subject's body mass index (BMI) should be between 19 and 30. * Screening Procedures: 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 GB 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) * If female and: * Of childbearing potential, is practicing an acceptable method of birth control for the duration of the study as judged by the investigator(s), such as condom with spermicide, diaphragm with spermicide, intrauterine device (IUD), or abstinence; or * 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 demonstrating a reactive screen for hepatitis B surface antigen, hepatitis C antibody or HIV antibody. * Subjects demonstrating a positive drug abuse screen when screened for this study. * Female subjects demonstrating a positive pregnancy screen. * Female subjects who are currently breastfeeding. * Subjects with a history of allergic response(s) to azithromycin 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 or report using tobacco products within 90 days of Period I dose administration. * Subjects who have taken any drug known to induce or inhibit hepatic drug metabolism in the 28 days prior to Period I dosing. * Subjects who report donating greater than 150 mL of blood within 28 days prior to Period I dosing. All subjects will be 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 28 days prior to Period I dosing. * Subjects who report taking any systemic prescription medication in the 14 days prior to Period I dosing. * Subjects who report an intolerance of direct venipuncture. * Subjects who report consuming an abnormal diet during the 28 days prior to Period I dosing. * Female subjects who report using implanted or injected hormonal contraceptives (birth control) during the 6 months prior to Period I dosing. * Female subjects who report using oral hormonal contraceptives (birth control) during the 14 days prior to Period I dosing. * Subjects who report having difficulty fasting or consuming standardized meals.
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
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Azithromycin (Test) First Azithromycin Oral Suspension 200 mg/5 mL (test) dosed in first period followed by Zithromax® Oral Suspension 200 mg/5 mL (reference) dosed in second period | 40 |
| Zithromax® (Reference) First Zithromax® Oral Suspension 200 mg/5 mL (reference) dosed in first period followed by Azithromycin Oral Suspension 200 mg/5 mL (test) dosed in second period | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout: 21 Days | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Azithromycin (Test) First | Zithromax® (Reference) First |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 79 Participants | 39 Participants | 40 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 4 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Native American | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 73 Participants | 38 Participants | 35 Participants |
| Region of Enrollment United States | 80 participants | 40 participants | 40 participants |
| Sex: Female, Male Female | 40 Participants | 18 Participants | 22 Participants |
| Sex: Female, Male Male | 40 Participants | 22 Participants | 18 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: One subject was excluded from statistical analysis due to emesis during sample collection period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azithromycin | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 4896.65 ng*h/mL | Standard Deviation 1620.06 |
| Zithromax® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 5022.64 ng*h/mL | Standard Deviation 2145.8 |
90% CI: [94.48, 107.65]
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: One subject was excluded from statistical analysis due to emesis during sample collection period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azithromycin | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 4357.47 ng*h/mL | Standard Deviation 1492.87 |
| Zithromax® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 4428.53 ng*h/mL | Standard Deviation 1936.89 |
90% CI: [95.18, 109.14]
Primary
Cmax - Maximum Observed Concentration
Bioequivalence based on Cmax
Time frame: Blood samples collected over 168 hour period
Population: One subject was excluded from statistical analysis due to emesis during sample collection period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azithromycin | Cmax - Maximum Observed Concentration | 465.66 ng/mL | Standard Deviation 222.06 |
| Zithromax® | Cmax - Maximum Observed Concentration | 449.85 ng/mL | Standard Deviation 192.95 |
90% CI: [94.84, 111.05]