Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study is to compare the relative bioavailability of ribavirin 200 mg tablets (manufactured by TEVA Pharmaceutical Industries, Ltd. and distributed by TEVA Pharmaceuticals USA) with that of COPEGUS™ 200 mg tablets (Roche) in healthy, adult, non-smoking, females (who are unable to become pregnant) under non-fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
1 x 200 mg, single-dose non-fasting
DRUGCOPEGUS™ 200 mg Tablets
1 x 200 mg, single-dose non-fasting
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
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, and a female whi is physically unable to become pregnant (postmenopausal for at least 6 months or surgically sterile). 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 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: * Hematology: hemoglobin, hematocrit, red blood cell count, platelets, and white blood cell count with differential. * Clinical Chemistry: creatinine, BUN, glucose, SGOT/AST, SGPT/ALT, bilirubin, and alkaline phosphatase. * Urine Analysis: pH, specific gravity, protein, glucose, ketones, bilirubin, occult blood, and cells. * HIV Screen: pre-study only * Hepatitis-B, C Screen: pre-study only * Drugs of Abuse Screen: (pre-study and at each check-in) * Subjects will be selected if all above are normal.
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 greater than 20% outside the normal range may be retested. 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 dems 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 or who are able (women with child bearing potential) to become pregnant during the study 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 of Drug Substance in Plasma) | Blood samples collected over a 72 hour period. | Bioequivalence based on Cmax. |
| AUC0-72 (Area Under the Concentration-time Curve From Time Zero to Time of 72 Hours) | Blood samples collected over a 72 hour period. | Bioequivalence based on AUC0-72. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Test (Ribavirin) First 200 mg Ribavirin Tablets test product dosed in first period followed by 200 mg Copegus® Tablets reference product dosed in the second period. | 13 |
| Reference (Copegus®) First 200 mg Copegus® Tablets reference product dosed in first period followed by 200 mg Ribavirin Tablets test product dosed in the second period. | 14 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout of 5 Weeks | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Test (Ribavirin) First | Reference (Copegus®) 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 | 12 Participants | 13 Participants | 25 Participants |
| Race/Ethnicity, Customized Asian | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Black | 4 participants | 6 participants | 10 participants |
| Race/Ethnicity, Customized Hispanic | 3 participants | 6 participants | 9 participants |
| Race/Ethnicity, Customized White | 5 participants | 2 participants | 7 participants |
| Region of Enrollment United States | 13 participants | 14 participants | 27 participants |
| Sex: Female, Male Female | 13 Participants | 14 Participants | 27 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Outcome results
Primary
AUC0-72 (Area Under the Concentration-time Curve From Time Zero to Time of 72 Hours)
Bioequivalence based on AUC0-72.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Ribavirin) | AUC0-72 (Area Under the Concentration-time Curve From Time Zero to Time of 72 Hours) | 7902.61 ng*h/mL | Standard Deviation 2529.513 |
| Reference (Copegus®) | AUC0-72 (Area Under the Concentration-time Curve From Time Zero to Time of 72 Hours) | 8041.413 ng*h/mL | Standard Deviation 2053.733 |
90% CI: [92.1, 101]
Primary
Cmax (Maximum Observed Concentration of Drug Substance in Plasma)
Bioequivalence based on Cmax.
Time frame: Blood samples collected over a 72 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Ribavirin) | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) | 755.154 ng/mL | Standard Deviation 245.223 |
| Reference (Copegus®) | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) | 749.615 ng/mL | Standard Deviation 200.341 |
90% CI: [93.1, 108]