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

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: Alprazolam Extended-Release 3 mg Tablets

Registration Number: NCT00829426

Lead Sponsor: Teva Pharmaceuticals USA

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 32

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Alprazolam	Alprazolam Extended-Release 3 mg Tablets	Alprazolam 3mg ER Tablet (test) dosed in first period followed by Xanax XR® 3 mg Tablet (reference) dosed in second period
Xanax XR®	Alprazolam Extended-Release 3 mg Tablets	Xanax XR® 3 mg Tablet (reference) dosed in first period followed by Alprazolam 3 mg ER Tablet (test) dosed in second period

Primary Outcome Measures

Name	Time	Method
Cmax - Maximum Observed Concentration	Blood samples collected over 72 hour period	Bioequivalence based on Cmax
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-inf
AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)	Blood samples collected over 72 hour period	Bioequivalence based on AUC0-t