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

Sponsor
Teva Pharmaceuticals USA (Industry)
Overall Status
Completed
CT.gov ID
NCT00829426
Collaborator
(none)
32
Enrollment
2
Locations
2
Arms
16
Patients Per Site

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Alprazolam Extended-Release 3 mg Tablets
  • Drug: Alprazolam Extended-Release 3 mg Tablets
 Phase 1

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 Design

Study Type:
Interventional
Actual Enrollment :
32 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Official Title:
A Relative Bioavailability Study of 3 mg Alprazolam Extended Release Tablets Under Fasting Conditions
Study Start Date :
Jun 1, 2005
Actual Primary Completion Date :
Jun 1, 2005
Actual Study Completion Date :
Jun 1, 2005

Arms and Interventions

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
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®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Bioequivalence Based on Cmax [Blood samples collected over 72 hour period]

      Cmax - Maximum Observed Concentration

    2. Bioequivalence Based on AUC0-inf [Blood samples collected over 72 hour period]

      AUC0-inf - Area under the concentration-time curve from time zero to infinity (extrapolated)

    3. Bioequivalence Based on AUC0-t [Blood samples collected over 72 hour period]

      AUC0-t - Area under the concentration-time curve from time zero to time of last non-zero concentration

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 PRACS Institute, Ltd. East Grand Forks Minnesota United States 56721
    2 PRACS Institute, Ltd. Fargo North Dakota United States 58104

    Sponsors and Collaborators

    • Teva Pharmaceuticals USA

    Investigators

    • Principal Investigator: James D. Carlson, Pharm. D., PRACS Institute, Ltd.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00829426
    Other Study ID Numbers:
    • R05-0166
    First Posted:
    Jan 27, 2009
    Last Update Posted:
    Jul 21, 2009
    Last Verified:
    Jun 1, 2009
    Keywords provided by , ,
    Bioequivalence
    Healthy Subjects
    Additional relevant MeSH terms:
    Alprazolam

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Alprazolam (Test) First Xanax® (Reference) First
    Arm/Group Description Alprazolam 3 mg ER Tablet (test) dosed in first period followed by Xanax XR® 3 mg Tablet (reference) dosed in second period Xanax XR® 3 mg Tablet (reference) dosed in first period followed by Alprazolam 3 mg Tablet (test) dosed in second period
    Period Title: First Intervention
    STARTED 16 16
    COMPLETED 16 16
    NOT COMPLETED 0 0
    Period Title: First Intervention
    STARTED 16 16
    COMPLETED 15 16
    NOT COMPLETED 1 0
    Period Title: First Intervention
    STARTED 15 16
    COMPLETED 15 16
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Alprazolam (Test) First Xanax® (Reference) First Total
    Arm/Group Description Alprazolam 3 mg ER Tablet (test) dosed in first period followed by Xanax XR® 3 mg Tablet (reference) dosed in second period Xanax XR® 3 mg Tablet (reference) dosed in first period followed by Alprazolam 3 mg Tablet (test) dosed in second period Total of all reporting groups
    Overall Participants 16 16 32
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    16
    100%
    16
    100%
    32
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    3
    18.8%
    1
    6.3%
    4
    12.5%
    Male
    13
    81.3%
    15
    93.8%
    28
    87.5%
    Race/Ethnicity, Customized (Number) [Number]
    White
    15
    93.8%
    12
    75%
    27
    84.4%
    Black
    0
    0%
    1
    6.3%
    1
    3.1%
    Asian
    0
    0%
    1
    6.3%
    1
    3.1%
    Native American or Alaskan Native
    1
    6.3%
    2
    12.5%
    3
    9.4%
    Region of Enrollment (participants) [Number]
    United States
    16
    100%
    16
    100%
    32
    100%

    Outcome Measures

    1. Primary Outcome
    Title Bioequivalence Based on Cmax
    Description Cmax - Maximum Observed Concentration
    Time Frame Blood samples collected over 72 hour period

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Alprazolam Xanax®
    Arm/Group Description Alprazolam 3 mg ER Tablet (test) dosed in first period followed by Xanax XR® 3 mg Tablet (reference) dosed in second period Xanax XR® 3 mg Tablet (reference) dosed in first period followed by Alprazolam 3 mg Tablet (test) dosed in second period
    Measure Participants 31 31
    Mean (Standard Deviation) [ng/mL]
    24.33
    (5.37)
    23.62
    (4.29)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Alprazolam, Xanax®
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments An analysis of variance (ANOVA) was performed on each of the pharmacokinetic parameters using SAS® software.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Ratio of Geometric Means
    Estimated Value 102.56
    Confidence Interval () 90%
    98.74 to 106.52
    Parameter Dispersion Type:
    Value:
    Estimation Comments Bioequivalence is established when 90% Confidence Interval falls withi 80-125.
    2. Primary Outcome
    Title Bioequivalence Based on AUC0-inf
    Description AUC0-inf - Area under the concentration-time curve from time zero to infinity (extrapolated)
    Time Frame Blood samples collected over 72 hour period

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Alprazolam Xanax®
    Arm/Group Description Alprazolam 3 mg ER Tablet (test) dosed in first period followed by Xanax XR® 3 mg Tablet (reference) dosed in second period Xanax XR® 3 mg Tablet (reference) dosed in first period followed by Alprazolam 3 mg Tablet (test) dosed in second period
    Measure Participants 31 31
    Mean (Standard Deviation) [ng*h/mL]
    668.79
    (250.55)
    725.34
    (291.34)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Alprazolam, Xanax®
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments An analysis of variance (ANOVA) was performed on each of the pharmacokinetic parameters using SAS® software.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Ratio of Geometric Means
    Estimated Value 92.88
    Confidence Interval () 90%
    90.34 to 95.48
    Parameter Dispersion Type:
    Value:
    Estimation Comments Bioequivalence is established when 90% Confidence Interval falls within 80 - 125
    3. Primary Outcome
    Title Bioequivalence Based on AUC0-t
    Description AUC0-t - Area under the concentration-time curve from time zero to time of last non-zero concentration
    Time Frame Blood samples collected over 72 hour period

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Alprazolam Xanax®
    Arm/Group Description Alprazolam 3 mg ER Tablet (test) dosed in first period followed by Xanax XR® 3 mg Tablet (reference) dosed in second period Xanax XR® 3 mg Tablet (reference) dosed in first period followed by Alprazolam 3 mg Tablet (test) dosed in second period
    Measure Participants 31 31
    Mean (Standard Deviation) [ng*h/mL]
    620.40
    (213.87)
    663.08
    (226.97)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Alprazolam, Xanax®
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments An analysis of variance (ANOVA) was performed on each of the pharmacokinetic parameters using SAS® software.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Ratio of Geometric Means
    Estimated Value 93.92
    Confidence Interval () 90%
    91.47 to 96.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments Bioequivalence is established when 90% Confidence Interval falls within 80 - 125

    Adverse Events

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Principal Investigator is not permitted to discuss or publish trial results.

    Results Point of Contact

    Name/Title Manager, Biopharmaceutics
    Organization Teva Pharmaceuticals USA
    Phone 1-866-384-5525
    Email clinicaltrialqueries@tevausa.com
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00829426
    Other Study ID Numbers:
    • R05-0166
    First Posted:
    Jan 27, 2009
    Last Update Posted:
    Jul 21, 2009
    Last Verified:
    Jun 1, 2009