Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this study was to compare the oral availability of a test product of Mycophenolate Mofetil 250 mg capsule to an equivalent oral dose of the commercially available reference product, CellCept® 250 mg capsule administered to healthy subjects under fed conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
DRUGMycophenolate Mofetil
250 mg Capsule
DRUGCellCept®
250 mg Capsule
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 must satisfy the following criteria to be considered for study participation: * Subject must be male or non-pregnant, non-breast-feeding female * Subject must be at least 18 years of age * Subject must have a Body Mass Index (BMI) between 19 and 30 kg/m2, inclusive, and body weight should be at least 50 kg (110 lbs) * Female Subjects - not surgically sterile or at least two years postmenopausal - must agree to utilize one of the following forms of contraception, if sexually active with a male partner, from screening through completion of the study. Approved forms of contraception are abstinence, double barrier (condom with spermicide, diaphragm with spermicide), intra-uterine device (IUD), or vasectomized partner (6 months minimum since vasectomy). * Subject must voluntarily consent to participate in this study and provide their written informed consent prior to the start of any study-specific procedures. * Subject is willing and able to remain in the study unit for the entire duration of each confinement period and return for any outpatient visits.
Exclusion criteria
Subjects may be excluded for any of the following: * History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition which, in the opinion of the Investigator would jeopardize the safety of the subject or the validity of the study results. * Has a clinically significant abnormal finding on the physical exam, medical history, ECG or clinical laboratory results at screening. * History or presence of allergic or adverse response to mycophenolate mofetil or related drugs. * Has been on a significantly abnormal diet during the four weeks preceding the first dose of study medication. * Has donated blood or plasma within 30 days prior to the first dose of study medication. * Has participated in another clinical trial within 30 days prior to the first dose of study medication. * Has used any over-the-counter (OTC) medication, including nutritional supplements, within 7 days prior to the first dose of study medication. * Has used any prescription medication, including hormonal contraceptive or hormonal replacement therapy, within 14 days prior to the first dose of study medication. * Has been treated with any known enzyme altering drugs such as barbiturates, phenothiazines, cimetidine, carbamazepine, etc., within 30 days prior to the first dose of study medication. * Has smoked or used tobacco products within 90 days prior to the first dose of study medication. * Is a female with a positive pregnancy test result. * Female who has used implanted hormonal contraceptives anytime during the 6 months prior to study start. * Has an intolerance to venipuncture. * Has difficulty fasting or consuming standard meals. * Has a positive urine screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, opiates) * Has a history of drug or alcohol abuse. * Has had a positive test for, or has been treated for hepatitis B, hepatitis C or HIV.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | Blood samples collected over 72 hour period | Bioequivalence based on Cmax - Maximum Drug Concentration |
| AUC0-inf | Blood samples collected over 72 hour period | Bioequivalence based on AUC0-inf - Area under concentration-time curve from time zero to infinity (extrapolated) |
| AUC0-t | Blood samples collected over 72 hour period | Bioequivalence based on AUC0-t - Area under concentration-time curve from time zero to time of last non-zero concentration |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mycophenolate Mofetil (Test) First Mycophenolate Mofetil 250 mg Capsule dosed in first period followed by Cellcept® 250 mg Capsule dosed in second period. | 30 |
| CellCept® (Reference) First CellCept® 250 mg Capsule dosed in first period followed by Mycophenolate Mofetil 250 mg Capsule dosed in second period. | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Mycophenolate Mofetil (Test) First | Total | CellCept® (Reference) First |
|---|---|---|---|
| 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 | 30 Participants | 60 Participants | 30 Participants |
| Race/Ethnicity, Customized American Indian | 5 Participants | 8 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 3 Participants | 11 Participants | 8 Participants |
| Race/Ethnicity, Customized White | 22 Participants | 40 Participants | 18 Participants |
| Region of Enrollment United States | 30 participants | 60 participants | 30 participants |
| Sex: Female, Male Female | 12 Participants | 30 Participants | 18 Participants |
| Sex: Female, Male Male | 18 Participants | 30 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 60 | 1 / 60 |
| serious Total, serious adverse events | 0 / 60 | 0 / 60 |
Outcome results
Primary
AUC0-inf
Bioequivalence based on AUC0-inf - Area under concentration-time curve from time zero to infinity (extrapolated)
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study was included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mycophenolate Mofetil (Test) | AUC0-inf | 14.6569 µg*h/mL | Standard Deviation 3.87 |
| CellCept® (Reference) | AUC0-inf | 14.2048 µg*h/mL | Standard Deviation 3.9281 |
90% CI: [100.23, 105.45]
Primary
AUC0-t
Bioequivalence based on AUC0-t - Area under concentration-time curve from time zero to time of last non-zero concentration
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study was included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mycophenolate Mofetil (Test) | AUC0-t | 13.8388 µg*h/mL | Standard Deviation 3.7728 |
| CellCept® (Reference) | AUC0-t | 13.4016 µg*h/mL | Standard Deviation 3.8398 |
90% CI: [100.51, 106.27]
Primary
Cmax
Bioequivalence based on Cmax - Maximum Drug Concentration
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study was included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mycophenolate Mofetil (Test) | Cmax | 2.8358 µg/mL | Standard Deviation 0.9056 |
| CellCept® (Reference) | Cmax | 2.9768 µg/mL | Standard Deviation 1.25 |
90% CI: [90.01, 104.55]