Alprazolam Extended-Release 3mg Tablets Bioequivalence Study Under Fasting Conditions

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Relative Bioavailability Study of 3 mg Alprazolam Extended Release Tablets Under Fasting Conditions

Conditions
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Healthy

Intervention / Treatment
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* Drug: Alprazolam Extended-Release 3 mg Tablets
* Drug: Alprazolam Extended-Release 3 mg Tablets


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alprazolam<br>Alprazolam 3mg ER Tablet (test) dosed in first period followed by Xanax XR® 3 mg Tablet (reference) dosed in second period | Drug: Alprazolam Extended-Release 3 mg Tablets<br>* 1 x 3 mg, single dose fasting<br>|
| Active Comparator: Xanax XR®<br>Xanax XR® 3 mg Tablet (reference) dosed in first period followed by Alprazolam 3 mg ER Tablet (test) dosed in second period | Drug: Alprazolam Extended-Release 3 mg Tablets<br>* 1 x 3 mg, single dose fasting<br>* Other names: XANAX XR®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioequivalence Based on Cmax | Cmax - Maximum Observed Concentration | Blood samples collected over 72 hour period | 
| Bioequivalence Based on AUC0-inf | AUC0-inf - Area under the concentration-time curve from time zero to infinity (extrapolated) | Blood samples collected over 72 hour period | 
| Bioequivalence Based on AUC0-t | AUC0-t - Area under the concentration-time curve from time zero to time of last non-zero concentration | Blood samples collected over 72 hour period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bioequivalence, Healthy Subjects