Clinical trial NCT00829426: Alprazolam Extended-Release 3mg Tablets Bioequivalence Study Under Fasting Conditions
Official title: A Relative Bioavailability Study of 3 mg Alprazolam Extended Release Tablets Under Fasting Conditions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Bioequivalence
Healthy Subjects
Lead sponsor: Teva Pharmaceuticals USA
Sponsor class: INDUSTRY
First posted: 2009-01-27
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cmax - Maximum Observed Concentration
timeFrame: Blood samples collected over 72 hour period
measure: AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)
timeFrame: Blood samples collected over 72 hour period
measure: AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)
timeFrame: Blood samples collected over 72 hour period
Secondary outcomes:
Other outcomes:
Locations:
city: East Grand Forks
country: United States
facility: PRACS Institute, Ltd.
state: Minnesota
city: Fargo
country: United States
facility: PRACS Institute, Ltd.
state: North Dakota
Study officials:
affiliation: PRACS Institute, Ltd.
name: James D. Carlson, Pharm. D.
role: PRINCIPAL_INVESTIGATOR
References: