This study will compare the relative bioavailability (rate and extent of absorption) of 3 mg Alprazolam Extended Release Tablets manufactured and distributed by TEVA Pharmaceuticals USA with that of 3 mg XANAX XR® Tablets by Pharmacia \& Upjohn Company following a single oral dose (1 x 3 mg extended release tablet) in healthy adult subjects administered under fasting conditions.
Detailed Description
Criteria for Evaluation: FDA Bioequivalence Criteria
Statistical Methods: FDA bioequivalence statistical methods
Outcome: Confidence interval fell within 80-125% therefore met the FDA Bioequivalence criteria; no drug related, serious, unexpected adverse events were reported during the study.
Inclusion Criteria:
* Screening Demographics: All subjects selected for this study will be healthy non-smoking men and women 18 years of age or older at the time of dosing. The subject's body mass index (BMI) should be less than or equal to 30.
* Screening procedures: Each subject will complete the screening process within 28 days prior to Period I dosing.
* Consent documents for both the screening evaluation and HIV antibody determination will be reviewed, discussed, and signed by each potential participant before full implementation of screening procedures.
* Screening will include general observations, physical examination, demographics, medical and medication history, an electrocardiogram, sitting blood pressure and heart rate, respiratory rate and temperature.
* The physical examination will include, but may not be limited to an evaluation of the cardiovascular, gastrointestinal, respiratory, and central nervous systems.
* The screening clinical laboratory procedures will include:
* Hematology: hematocrit, hemoglobin, WBC count with differential, RBC count, platelet count;
* Clinical Chemistry: serum creatinine, BUN, glucose, AST(GOT), ALT(GPT), albumin, total bilirubin, total protein, and alkaline phosphatase;
* HIV antibody, hepatitis B surface antigen, hepatitis C antibody screens;
* Urinalysis: by dipstick; full microscopic examination if dipstick positive; and
* Urine Drug Screen: ethyl alcohol, amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine metabolites, opiates, and phencyclidine.
* Serum Pregnancy Screen (female subjects only)
* FSH (to verify postmenopausal status; female subjects only)
* If female and:
* is postmenopausal for at least 1 year and has a serum FSH level ≥ 20mIU/mL; or
* is surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy).
Exclusion Criteria:
* Subjects with a recent history of dug or alcohol addiction or abuse.
* subjects with the presence of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or neurologic system(s) or psychiatric disease (as determined by the clinical investigators).
* Subjects whose clinical laboratory test values are outside the accepted reference range and when confirmed on re-examination are deemed to be clinically significant.
* Subjects demonstrating a reactive screen for hepatitis B surface antigen, hepatitis C antibody or HIV antibody.
* Subjects demonstrating positive drug abuse screen when screened for this study.
* Female subjects demonstrating a positive pregnancy screen.
* Female subjects who are currently breast-feeding.
* Subjects with a history of allergic response(s) to alprazolam or related drugs.
* Subjects with a history of clinically significant allergies including drug allergies.
* Subjects with a clinically significant illness during the 4 weeks prior to Period I dosing (as determined by the clinical investigators).
* Subjects who currently use or report using tobacco products within 90 days of Period I dose administration.
* Subjects who have taken any drug known to induce or inhibit hepatic drug metabolism in the 28 days prior to Period I dosing.
* Subjects who report donating greater than 150 mL of blood within 30 days prior to Period I dosing. All subjects will be advised not to donate plasma for four weeks after completing the study.
* Subjects who report receiving any investigational drug within 28 days prior to Period I dosing.
* Subjects who report taking any systemic prescription medication in the 14 days prior to Period I dosing.
* Subjects who report an intolerance of direct venipuncture.
* Subjects who report consuming an abnormal diet during the 28 days prior to Period I dosing.
Locations (2)
PRACS Institute, Ltd.
East Grand Forks, Minnesota, United States
PRACS Institute, Ltd.
Fargo, North Dakota, United States
Outcomes
Primary Outcomes
Cmax - Maximum Observed Concentration
Bioequivalence based on Cmax
Time frame: Blood samples collected over 72 hour period
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 72 hour period
AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)
Bioequivalence based on AUC0-t
Time frame: Blood samples collected over 72 hour period