Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
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.
Interventions
1 x 3 mg, single dose fasting
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Alprazolam (Test) First Alprazolam 3 mg ER Tablet (test) dosed in first period followed by Xanax XR® 3 mg Tablet (reference) dosed in second period | 16 |
| Xanax® (Reference) First Xanax XR® 3 mg Tablet (reference) dosed in first period followed by Alprazolam 3 mg Tablet (test) dosed in second period | 16 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout: 7 Days | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Alprazolam (Test) First | Xanax® (Reference) First |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 16 Participants | 16 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native American or Alaskan Native | 3 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 27 Participants | 15 Participants | 12 Participants |
| Region of Enrollment United States | 32 participants | 16 participants | 16 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 28 Participants | 13 Participants | 15 Participants |
Outcome results
Primary
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
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprazolam | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 668.79 ng*h/mL | Standard Deviation 250.55 |
| Xanax® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 725.34 ng*h/mL | Standard Deviation 291.34 |
90% CI: [90.34, 95.48]
Primary
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
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprazolam | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 620.40 ng*h/mL | Standard Deviation 213.87 |
| Xanax® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 663.08 ng*h/mL | Standard Deviation 226.97 |
90% CI: [91.47, 96.44]
Primary
Cmax - Maximum Observed Concentration
Bioequivalence based on Cmax
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study were included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprazolam | Cmax - Maximum Observed Concentration | 24.33 ng/mL | Standard Deviation 5.37 |
| Xanax® | Cmax - Maximum Observed Concentration | 23.62 ng/mL | Standard Deviation 4.29 |
90% CI: [98.74, 106.52]