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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Alprazolam Extended-Release 3 mg Tablets

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • East Grand Forks, Minnesota, United States, 56721
      • PRACS Institute, Ltd.
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • PRACS Institute, Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alprazolam; 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; 1 x 3 mg, single dose fasting; Other Names: XANAX XR®
Active Comparator: Xanax XR®; 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; 1 x 3 mg, single dose fasting; Other Names: XANAX XR®

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Teva Pharmaceuticals USA

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): June 1, 2005
• Study Completion (Actual): June 1, 2005

Study Registration Dates

• First Submitted: January 26, 2009
• First Submitted That Met QC Criteria: January 26, 2009
• First Posted (Estimate): January 27, 2009

Study Record Updates

• Last Update Posted (Estimate): July 21, 2009
• Last Update Submitted That Met QC Criteria: June 18, 2009
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: Bioequivalence; Healthy Subjects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Alprazolam
• Other Study ID Numbers: R05-0166