Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study is to compare the relative bioequivalence of a test clarithromycin extended release formulation to an equivalent oral dose of the commercially available extended release clarithromycin in a test population of 66 adult subjects under fasting 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
* Sex: Males or females who are surgically sterile or have been post-menopausal for at least 6 months; similar proportions of each preferred. * Age: At least 18 years. * 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 subjects 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: 1. Laboratory Tests: Hemoglobin, hematocrit, RBC, WBC, differential count, serum electrolytes (Nz, K, Cl), fasting blood glucose, BUN, bilirubin,m 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. Post-menopausal females will have an FSH (Follicle Stimulating Hormone) level performed to confirm post-menopausal status. 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. 2. 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: 1. History of treatment for alcoholism, substance abuse, or drug abuse within past 24 months. 2. History of malignancy, stroke, diabetes, cardiac, renal or liver disease, or other serious illness. 3. History of treatment for any gastrointestinal disorder within the past 5 years. 4. History of treatment for asthma within the past five (5) years. 5. History of diarrhea within 24 hours prior to dosing. 6. Females who are pregnant or lactating. 7. History of hypersensitivity to clarithromycin or any macrolide antibiotic. C. Conditions upon screening which might contraindicate or require that caution be used in the administration of dexmethylphenidate hydrochloride, including: 1. Sitting systolic blood pressure below 90 mm Hg, or diastolic pressure below 50 mm Hg. 2. 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.). Three (3) consecutive months abstinence is required.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration | Blood samples collected over 36 hour period | Bioequivalence based on Cmax |
| AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | Blood samples collected over 36 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 | Blood samples collected over 36 hour period | Bioequivalence based on AUC0-t |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Clarithromycin (Test) First Clarithromycin 500 mg ER Tablet (test) dosed in first period followed by Biaxin® XL 500 mg Filmtab® (reference) dosed in second period. | 33 |
| Biaxin® XL (Reference) First Biaxin® XL 500 mg Filmtab® (reference) dosed in first period followed by Clarithromycin 500 mg ER Tablet (test) dosed in second period | 33 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 1 | 0 |
| Washout | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Clarithromycin (Test) First | Biaxin® XL (Reference) First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 32 Participants | 64 Participants |
| Race/Ethnicity, Customized Black | 9 Participants | 4 Participants | 13 Participants |
| Race/Ethnicity, Customized Caucasian | 24 Participants | 29 Participants | 53 Participants |
| Region of Enrollment United States | 33 participants | 33 participants | 66 participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Male | 28 Participants | 27 Participants | 55 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 36 hour period
Population: AUCinf could not be estimated for some subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clarithromycin | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 10255.3 ng*h/mL | Standard Deviation 4102.34 |
| Biaxin® XL | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 11767.7 ng*h/mL | Standard Deviation 5131.84 |
90% CI: [80.1, 93.4]
Primary
AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration
Bioequivalence based on AUC0-t
Time frame: Blood samples collected over 36 hour period
Population: Data from 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 | 9735.5 ng*h/mL | Standard Deviation 3813.66 |
| Biaxin® XL | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration | 11136.6 ng*h/mL | Standard Deviation 4412.82 |
90% CI: [81, 93.8]
Primary
Cmax - Maximum Observed Concentration
Bioequivalence based on Cmax
Time frame: Blood samples collected over 36 hour period
Population: Data from subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clarithromycin | Cmax - Maximum Observed Concentration | 640.08 ng/mL | Standard Deviation 214.223 |
| Biaxin® XL | Cmax - Maximum Observed Concentration | 640.11 ng/mL | Standard Deviation 231.752 |
90% CI: [93.3, 107.1]