Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study is to compare the relative bioavailability of famciclovir 500 mg tablets (Novopharm Limited) with that of FAMVIR® 500 mg tablets (Novartis) in healthy adult subjects under non-fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
1 x 500 mg, single-dose fasting
1 x 500 mg, single-dose fasting
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 at least 18 years of age. * 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 female subject will be give a serum pregnancy test as part of the pre-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 check-in each study period. Electrocardiograms of all participating subjects will be recorded before initiation of the study and filed with each subject's case report forms.
Exclusion criteria
* Subjects with a history of alcoholism or drug addiction (during past 2 years), or serious gastrointestinal, renal, hepatic, or cardiovascular disease, tuberculosis, epilepsy, asthma (during past 5 years), diabetes, psychosis or glaucoma will not be eligible for this study. * Subjects whose clinical laboratory test values are outside the normal range may be retested at the discretion of the clinical investigator. 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 deems the result to not be significant. * Subjects who have a history of allergic responses to the class of drug being tested should be excluded form the study. * 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 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, breast-feeding, or who are likely to become pregnant during the study will not be allowed to participate. Female subjects of child bearing potential must either abstain from sexual intercourse or use a reliable barrier method (e.g. condom, IUD) of contraception during the course of the study (first dosing until last blood collection) or they will not be allowed to participate. Subjects who have used implanted or injected hormonal contraceptives anytime during the 6 months prior to study dosing, or used oral hormonal contraceptives within 14 days before dosing 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax = Maximum Observed Concentration. | Blood samples collected over a 16 hour period. | Bioequivalence based on Cmax. |
| AUC0-t = Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (Per Participant) | Blood samples collected over a 16 hour period. | Bioequivalence based on AUC0-t. |
| AUC0-inf = Area Under the Concentration-time Curve From Time Zero to Infinity. | Blood samples collected over a 16 hour period. | Bioequivalence based on AUC0-inf. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Famciclovir First 500 mg Famciclovir Tablets test product dosed in first period followed by 500 mg Famvir® Tablets reference product dosed in the second period. | 18 |
| Famvir® First 500 mg Famvir® Tablets reference product dosed in first period followed by 500 mg Famciclovir Tablets test product dosed in the second period. | 18 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 1 | 0 |
| First Intervention | Intolerance to Venopuncture | 0 | 1 |
| Second Intervention | Adverse Event | 1 | 0 |
| Washout of 7 Days | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Famciclovir First | Famvir® 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 | 18 Participants | 18 Participants | 36 Participants |
| Race/Ethnicity, Customized Black | 3 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Unknown | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 14 participants | 15 participants | 29 participants |
| Region of Enrollment United States | 18 participants | 18 participants | 36 participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 11 Participants | 11 Participants | 22 Participants |
Outcome results
Primary
AUC0-inf = Area Under the Concentration-time Curve From Time Zero to Infinity.
Bioequivalence based on AUC0-inf.
Time frame: Blood samples collected over a 16 hour period.
Population: All participants that completed the study had their samples analyzed. Data from one withdrawn subject was also included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Famciclovir | AUC0-inf = Area Under the Concentration-time Curve From Time Zero to Infinity. | 9685.718 ng*h/mL | Standard Deviation 1952.136 |
| Famvir® | AUC0-inf = Area Under the Concentration-time Curve From Time Zero to Infinity. | 9660.396 ng*h/mL | Standard Deviation 1820.452 |
90% CI: [97.7, 103]
Primary
AUC0-t = Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (Per Participant)
Bioequivalence based on AUC0-t.
Time frame: Blood samples collected over a 16 hour period.
Population: All participants that completed the study had their samples analyzed. Data from one withdrawn subject was also included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Famciclovir | AUC0-t = Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (Per Participant) | 9568.663 ng*h/mL | Standard Deviation 1944.418 |
| Famvir® | AUC0-t = Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (Per Participant) | 9533.607 ng*h/mL | Standard Deviation 1816.697 |
90% CI: [97.9, 103]
Primary
Cmax = Maximum Observed Concentration.
Bioequivalence based on Cmax.
Time frame: Blood samples collected over a 16 hour period.
Population: All participants that completed the study had their samples analyzed. Data from one withdrawn subject was also included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Famciclovir | Cmax = Maximum Observed Concentration. | 2557.03 ng/mL | Standard Deviation 473.169 |
| Famvir® | Cmax = Maximum Observed Concentration. | 2713.939 ng/mL | Standard Deviation 757.822 |
90% CI: [87.8, 107]