Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The purpose of this study is to evaluate the relative bioavailability of the test formulation of terbinafine tablets with an already marketed reference formulation Lamisil® (Novartis Pharmaceuticals), under fasted conditions in healthy, non-tobacco using male and female adult subjects.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
1 x 250 mg
1 x 250 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
* Males and females, 18 years or older inclusive with a body mass index (BMI) of 30 or less. * Good health as determined by lack of clinically significant abnormalities in health assessments performed at screening. * Signed and dated informed consent form, which meets all criteria of current FDA regulations * If female and of child bearing potential subjects must be prepared to abstain from sexual intercourse or use a reliable barrier method of contraception (e.g. condom, IUD) during the duration of the study. Female subjects who have used oral contraceptives within 14 days or injected hormonal contraceptives within 180 days of dosing will not be allowed to participate.
Exclusion criteria
* If female, pregnant, lactating or likely to become pregnant during the study. * History of allergy or sensitivity to terbinafine, or history of any drug hypersensitivity or intolerance which, in the opinion of the Investigator, would compromise the safety of the subject or the study. * Significant history or current evidence of chronic evidence of chronic infectious disease, system disorder ot organ dysfunction. * Presence of gastrointestinal disease ot history of malabsorption within the last year. * History of psychiatric disorders occuring within the last two years that required hospitalization or medication. * Presence of a medical condition requiring regular treatment with prescription drugs. * Use of pharmacologic agents known to significantly induce or inhibit drug-metabolizing enzymes. within 30 days prior to dosing. * Receipt of any drug as part of a research study within 30 days prior to dosing. * Drug or alcohol addition requiring treatment in the past 12 months. * Donation or significant loss of whole blood (480 ml or more) within 30 days or plasma within 14 days prior to dosing. * Positive test results for drug of abuse at screening. * Tobacco user within 90 days of the first study dose. * Unable, or unwilling to tolerate multiple venipunctures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration - Terbinafine in Plasma | Blood samples collected over 144 hour period | Bioequivalence based on Cmax |
| AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Terbinafine in Plasma | Blood samples collected over 144 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) - Terbinafine in Plasma | Blood samples collected over 144 hour period | Bioequivalence based on AUC0-t |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Terbinafine (Test) First Terbinafine HCl 250 mg Tablet (test) dosed in first period followed by Lamisil® 250 mg Tablet (reference) dosed in second period | 14 |
| Lamisil® (Reference) First Lamisil® 250 mg Tablet (reference) dosed in first period followed by Terbinafine 250 mg Tablet (test) dosed in second period | 14 |
| Total | 28 |
Baseline characteristics
| Characteristic | Lamisil® (Reference) First | Terbinafine (Test) 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 | 14 Participants | 14 Participants | 28 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Biracial | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 5 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized Caucasian | 7 Participants | 8 Participants | 15 Participants |
| Race/Ethnicity, Customized Hispanic | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment United States | 14 participants | 14 participants | 28 participants |
| Sex: Female, Male Female | 3 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 11 Participants | 14 Participants | 25 Participants |
Outcome results
Primary
AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Terbinafine in Plasma
Bioequivalence based on AUC0-inf
Time frame: Blood samples collected over 144 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Terbinafine | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Terbinafine in Plasma | 4425 ng*h/mL | Standard Deviation 1733 |
| Lamisil® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Terbinafine in Plasma | 4062 ng*h/mL | Standard Deviation 2020 |
90% CI: [82.7, 118.4]
Primary
AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) - Terbinafine in Plasma
Bioequivalence based on AUC0-t
Time frame: Blood samples collected over 144 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Terbinafine | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) - Terbinafine in Plasma | 3795 ng*h/mL | Standard Deviation 1498 |
| Lamisil® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) - Terbinafine in Plasma | 3765 ng*h/mL | Standard Deviation 1636 |
90% CI: [95, 110.5]
Primary
Cmax - Maximum Observed Concentration - Terbinafine in Plasma
Bioequivalence based on Cmax
Time frame: Blood samples collected over 144 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Terbinafine | Cmax - Maximum Observed Concentration - Terbinafine in Plasma | 840.2 ng/mL | Standard Deviation 310.8 |
| Lamisil® | Cmax - Maximum Observed Concentration - Terbinafine in Plasma | 873.2 ng/mL | Standard Deviation 299.3 |
90% CI: [85.8, 105.4]