Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this randomized, single-dose, two-way crossover evaluation is to compare the relative bioequivalence of a test azithromycin formulation (TEVA Pharmaceuticals USA) to an equivalent oral dose of the commercially available azithromycin (Zithromax®, Pfizer, Inc.) in a test population of 24 adult subjects under fed conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
1 x 600mg, single-dose fed
1 x 600mg, single-dose fed
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
* Sex:Non-smoking Male or Female; similar proportions of each preferred. * Age: At least 18 years. * Weight: BMI less than 30. * Qualifying subjects must be in good health and physical condition as determined by medical history, complete physical examination, and laboratory tests, all obtained within four (4) weeks prior to study start. The subject may not have a history of significant past illness expected to affect the investigation. The normal status of subjects will be confirmed by the following procedures: * Laboratory Tests: hemoglobin, hematocrit, RBC, WBC, differential count, serum electrolytes (Na, K, Cl), fasting blood glucose, BUN, bilirubin, creatinine, AST, ALT, LD, alkaline phosphatase, and urinalysis. HIV, Hepatitis B, Hepatitis C, and drugs of abuse testing will be done for screening purposes only. urine drugs of abuse testing will be repeated at each check-in. Female subjects will have a serum pregnancy test done at screening and a urine pregnancy test prior to each study period at check-in. Laboratory values which are greater than ± 20% of the normal range will not qualify unless specifically accepted (with comment) by the Principal Investigator. Results of HIV, Hepatitis B, Hepatitis C, and drugs of abuse must be negative or non-reactive for the subject to qualify for the study. * Electrocardiogram: A 12-lead electrocardiogram (ECG) will be obtained for all subjects. The original tracings, plus interpretation, will be included in the case report form packet. * Subjects must read and sign the Consent Form.
Exclusion criteria
* Subjects not complying with the above inclusion criteria must be excluded from the study. * In addition, any one of the conditions listed below will exclude a subject from the study: * History of treatment for alcoholism, substance abuse, or drug abuse within past 24 months. * History of malignancy, stroke, diabetes, cardiac, renal or liver disease, or other serious illness. * History of treatment for asthma within the past five (5) years. * History of treatment for any gastrointestinal disorder within the past five (5) years. * History of hepatic function impairment. * Females who are pregnant or lactating. * History of hypersensitivity to azithromycin, erythromycin, or any macrolide antibacterial agent. * Conditions upon screening which might contraindicate or require that caution be used in the administration of azithromycin, including: * Sitting systolic blood pressure below 90 mmHg, or diastolic pressure below 50 mmHg. * Heart rate less than 50 beats per minute after a 5-minute rest in a seated position. * Inability to read and/or sign the consent form. * Treatment with any other investigational drug during the four (4) weeks prior to the initial dosing for this study. * Subjects who have donated blood within four (4) weeks prior to the initial dosing for this study. * Subjects who smoke or use tobacco products or are currently using nicotine products (patches, gums, etc.) At least three (4) consecutive months of abstinence is required.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration - Azithromycin in Plasma | 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) - Azithromycin in Plasma | 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)- Azithromycin in Plasma | 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 600 mg tablet (test) dosed in first period followed by Zithromax® 600 mg tablet (reference) dosed in second period | 12 |
| Zithromax® (Reference) First Zithromax® 600 mg tablet (reference) dosed in first period followed by Azithromycin 600 mg tablet (test) dosed in second period | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Azithromycin (Test) First | Zithromax® (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 | 12 Participants | 12 Participants | 24 Participants |
| Race/Ethnicity, Customized Black | 5 Participants | 3 Participants | 8 Participants |
| Race/Ethnicity, Customized Caucasian | 7 Participants | 9 Participants | 16 Participants |
| Region of Enrollment United States | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 15 Participants |
Outcome results
Primary
AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Azithromycin in Plasma
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 |
|---|---|---|---|
| Azithromycin | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Azithromycin in Plasma | 7025.920 ng*h/mL | Standard Deviation 1583.546 |
| Zithromax® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Azithromycin in Plasma | 6964.092 ng*h/mL | Standard Deviation 1621.163 |
90% CI: [96, 106.03]
Primary
AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)- Azithromycin in Plasma
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 |
|---|---|---|---|
| Azithromycin | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)- Azithromycin in Plasma | 6132.710 ng*h/mL | Standard Deviation 1483.937 |
| Zithromax® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)- Azithromycin in Plasma | 6063.795 ng*h/mL | Standard Deviation 1436.447 |
90% CI: [96.05, 106.49]
Primary
Cmax - Maximum Observed Concentration - Azithromycin in Plasma
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 |
|---|---|---|---|
| Azithromycin | Cmax - Maximum Observed Concentration - Azithromycin in Plasma | 561.556 ng/mL | Standard Deviation 199.349 |
| Zithromax® | Cmax - Maximum Observed Concentration - Azithromycin in Plasma | 592.311 ng/mL | Standard Deviation 255.261 |
90% CI: [84.77, 106.04]