Alprazolam Extended-Release 3mg Tablets Bioequivalence Study Under Non-fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00830024
• Collaborator: (none)
• Enrollment: 36
• Locations: 2
• Arms: 2
• Patients Per Site: 18

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 non-fasting conditions.

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

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 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 Non-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 (test) Alprazolam 3 mg 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 non-fasting
Active Comparator: Xanax XR® Xanax XR® 3 mg Tablet (test) 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 non-fasting; Other Names: XANAX XR®

Outcome Measures

Primary Outcome Measures

1. Cmax - Maximum Observed Concentration [Blood samples collected over 72 hour period]

   Bioequivalence based on Cmax

2. 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

3. 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

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.

• ClinicalTrials.gov Identifier: NCT00830024
• Other Study ID Numbers: R05-0167
• First Posted: Jan 27, 2009
• Last Update Posted: Sep 11, 2009
• Last Verified: Sep 1, 2009

• Keywords provided by , ,: Bioequivalence; Healthy Subjects
• Additional relevant MeSH terms: Alprazolam

Study Results

Participant Flow

Arm/Group Title	Test First	Reference First
Arm/Group Description	Alprazolam Extended Release Tablet 3 mg test product dosed in first period followed by Xanax XR® Tablet 3 mg reference product dosed in second period	Xanax XR® Tablet 3 mg reference product dosed in first period followed by Alprazolam Extended Release Tablet 3 mg test product dosed in second period
Period Title: First Intervention
STARTED	18	18
COMPLETED	18	18
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	18	18
COMPLETED	17	18
NOT COMPLETED	1	0
Period Title: First Intervention
STARTED	17	18
COMPLETED	17	18
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Test First	Reference First	Total
Arm/Group Description	Alprazolam Extended Release Tablet 3 mg test product dosed in first period followed by Xanax XR® Tablet 3 mg reference product dosed in second period	Xanax XR® Tablet 3 mg reference product dosed in first period followed by Alprazolam Extended Release Tablet 3 mg test product dosed in second period	Total of all reporting groups
Overall Participants	18	18	36
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	17 94.4%	18 100%	35 97.2%
>=65 years	1 5.6%	0 0%	1 2.8%
Sex: Female, Male (Count of Participants)
Female	2 11.1%	2 11.1%	4 11.1%
Male	16 88.9%	16 88.9%	32 88.9%
Race/Ethnicity, Customized (Number) [Number]
White	17 94.4%	17 94.4%	34 94.4%
Black	0 0%	1 5.6%	1 2.8%
Asian	1 5.6%	0 0%	1 2.8%
Region of Enrollment (participants) [Number]
United States	18 100%	18 100%	36 100%

Outcome Measures

1. Primary Outcome

Title	Cmax - Maximum Observed Concentration
Description	Bioequivalence based on Cmax
Time Frame	Blood samples collected over 72 hour period

Outcome Measure Data

Analysis Population Description

Data from all subjects who completed the study were included in the statistical analysis.

Arm/Group Title	Alprazolam	Xanax XR®
Arm/Group Description	Alprazolam Extended Release Tablet 3 mg test product dosed in either period	Xanax XR® Tablet 3 mg reference product dosed in either period
Measure Participants	35	35
Mean (Standard Deviation) [ng/mL]	28.79 (6.35)	28.95 (5.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alprazolam, Xanax XR®
	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	Geometric Test/Ref Ratio x 100
	Estimated Value	98.75
	Confidence Interval	() 90%; 93.35 to 104.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80 - 125

2. Primary Outcome

Title	AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)
Description	Bioequivalence based on AUC0-inf
Time Frame	Blood samples collected over 72 hour period

Outcome Measure Data

Analysis Population Description

Data from all subjects who completed the study were included in the statistical analysis.

Arm/Group Title	Alprazolam	Xanax XR®
Arm/Group Description	Alprazolam Extended Release Tablet 3 mg test product dosed in either period	Xanax XR® Tablet 3 mg reference product dosed in either period
Measure Participants	35	35
Mean (Standard Deviation) [ng*h/mL]	650.91 (249.36)	683.25 (289.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alprazolam, Xanax XR®
	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	Geometric Test/Ref Ratio x 100
	Estimated Value	95.94
	Confidence Interval	() 90%; 91.76 to 100.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80 - 125

3. Primary Outcome

Title	AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)
Description	Bioequivalence based on AUC0-t
Time Frame	Blood samples collected over 72 hour period

Outcome Measure Data

Analysis Population Description

Data from all subjects who completed the study were included in the statistical analysis.

Arm/Group Title	Alprazolam	Xanax XR®
Arm/Group Description	Alprazolam Extended Release Tablet 3 mg test product dosed in either period	Xanax XR® Tablet 3 mg reference product dosed in either period
Measure Participants	35	35
Mean (Standard Deviation) [ng*h/mL]	600.24 (199.80)	626.54 (216.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alprazolam, Xanax XR®
	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	Geometric Test/Ref Ratio x 100
	Estimated Value	95.89
	Confidence Interval	() 90%; 91.67 to 100.31
	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.