Clarithromycin 500 mg Tablets Under Fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00835692
• Collaborator: (none)
• Enrollment: 60
• Locations: 2
• Arms: 2
• Patients Per Site: 30

Study Details

Study Description

Brief Summary

This study will compare the relative bioavailability (rate and extent of absorption) of 500 mg Clarithromycin Tablets with that of 500 mg BIAXIN® Tablets following a single oral dose (1 x 500 mg tablet) in healthy adult subjects under fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Clarithromycin; Drug: Biaxin®	Phase 1

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Relative Bioavailability Study of 500 mg Clarithromycin Tablets Under Fasting COnditions
• Study Start Date: Sep 1, 2002
• Actual Primary Completion Date: Sep 1, 2002
• Actual Study Completion Date: Sep 1, 2002

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Clarithromycin Tablets Clarithromycin 500 mg Tablet (test) dosed in first period followed by Biaxin® 500 mg Tablet (reference) dosed in second period	Drug: Clarithromycin; 500 mg Tablet
Active Comparator: Biaxin® Tablets Biaxin® 500 mg Tablet (reference) dosed in first period followed by Clarithromycin 500 mg Tablet (test) dosed in second period	Drug: Biaxin®; 500 mg Tablet

Outcome Measures

Primary Outcome Measures

1. Cmax - Maximum Observed Concentration [Blood samples collected over 48 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 48 hour period]

   Bioequivalence based on AUC0-t

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 48 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:

All subjects selected for this study will be healthy men or 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.

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

• URINE DRUG SCREEN: ethyl alcohol, amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine metabolites, opiates and phencyclidine

• SERUM PREGNANCY SCREEN (female subjects only)

• FOLLICLE STIMULATING HORMONE (FSH; female subjects only): verify postmenopausal status

If female and :

is postmenopausal for at least 1 year; or is surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy).

Exclusion Criteria:

Subjects with a recent history of drug 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 demonstration a positive hepatitis B surface antigen screen, hepatitis C antibody screen or a reactive HIV antibody screen.

Subjects demonstrating a positive drug abuse screen when screened for this study.

Female subjects who are currently breast feeding. Female subjects who are demonstrating a positive pregnancy screen. Subjects with a history of allergic response(s) to Clarithromycin 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 reports using tobacco or nicotine-containing products within 90 days prior to Period I dosing.

Subjects who have taken any drug known to induce or inhibit hepatic drug metabolism in the 30 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 by advised not to donate blood for four weeks after completing the study.

Subjects who have donated plasma (e.g. plasmapheresis) within 14 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 30 days prior to Period I dosing.

Subjects who report taking any prescription medication in the 14 days prior to Period I dosing, with the exception of topical products without systemic absorption.

Subjects who have been on an abnormal diet during the 28 days prior to Period I dosing.

Subjects who report an intolerance of direct venipuncture.

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00835692
• Other Study ID Numbers: R02-663
• First Posted: Feb 4, 2009
• Last Update Posted: Sep 11, 2009
• Last Verified: Sep 1, 2009

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

Study Results

Participant Flow

Arm/Group Title	Clarithromycin (Test) First	Biaxin® (Reference) First
Arm/Group Description	Clarithromycin 500 mg Tablet (test) dosed in first period followed by Biaxin® 500 mg Tablet (reference) dosed in second period	Biaxin® 500 mg Tablet (reference) dosed in first period followed by Clarithromycin 500 mg Tablet dosed in second period
Period Title: First Intervention
STARTED	28	28
COMPLETED	27	28
NOT COMPLETED	1	0
Period Title: First Intervention
STARTED	27	28
COMPLETED	27	28
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	27	28
COMPLETED	27	28
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Clarithromycin (Test) First	Biaxin® (Reference) First	Total
Arm/Group Description	Clarithromycin 500 mg Tablet (test) dosed in first period followed by Biaxin® 500 mg Tablet (reference) dosed in second period	Biaxin® 500 mg Tablet (reference) dosed in first period followed by Clarithromycin 500 mg Tablet dosed in second period	Total of all reporting groups
Overall Participants	28	28	56
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	28 100%	28 100%	56 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	2 7.1%	2 7.1%	4 7.1%
Male	26 92.9%	26 92.9%	52 92.9%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	27 96.4%	23 82.1%	50 89.3%
Hispanic	1 3.6%	2 7.1%	3 5.4%
Asian	0 0%	2 7.1%	2 3.6%
Black	0 0%	1 3.6%	1 1.8%
Region of Enrollment (participants) [Number]
United States	28 100%	28 100%	56 100%

Outcome Measures

1. Primary Outcome

Title	Cmax - Maximum Observed Concentration
Description	Bioequivalence based on Cmax
Time Frame	Blood samples collected over 48 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	Clarithromycin	Biaxin®
Arm/Group Description	Clarithromycin 500 mg Tablet (test) dosed in either period	Biaxin® 500 mg Tablet (reference) dosed in either period
Measure Participants	55	55
Mean (Standard Deviation) [ng/mL]	2170.964 (690.215)	2214.636 (763.844)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clarithromycin, Biaxin®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The pharmacokinetic parameters will be evaluated statistically by an analysis of variance (ANOVA) appropriate for the experimental design of this study.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Test/Ref Ratio of LS Mean x 100
	Estimated Value	98.4
	Confidence Interval	() 90%; 91.5 to 106
	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-t
Time Frame	Blood samples collected over 48 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	Clarithromycin	Biaxin®
Arm/Group Description	Clarithromycin 500 mg Tablet (test) dosed in either period	Biaxin® 500 mg Tablet (reference) dosed in either period
Measure Participants	55	55
Mean (Standard Deviation) [ng*h/mL]	17380.442 (6167.362)	18481.089 (5728.638)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clarithromycin, Biaxin®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The pharmacokinetic parameters will be evaluated statistically by an analysis of variance (ANOVA) appropriate for the experimental design of this study.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Test/Ref Ratio of LS Means x 100
	Estimated Value	93.5
	Confidence Interval	() 90%; 89.6 to 97.6
	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 48 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	Clarithromycin	Biaxin®
Arm/Group Description	Clarithromycin 500 mg Tablet (test) dosed in either period	Biaxin® 500 mg Tablet (reference) dosed in either period
Measure Participants	55	55
Mean (Standard Deviation) [ng*h/mL]	17265.639 (6136.361)	18362.380 (5719.467)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clarithromycin, Biaxin®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The pharmacokinetic parameters will be evaluated statistically by an analysis of variance (ANOVA) appropriate for the experimental design of this study.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Test/Ref Ratio of LS Means x 100
	Estimated Value	93.5
	Confidence Interval	() 90%; 89.5 to 97.7
	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.