Clarithromycin 500 mg Extended Release Tablets Under Fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00840411
• Collaborator: (none)
• Enrollment: 66
• Location: 1
• Arms: 2
• Duration (Days): 30
• Patients Per Site Per Month: 67

Study Details

Study Description

Brief Summary

The objective of this study is to compare the relative bioequivalence of a test clarithromycin extended release formulation to an equivalent oral dose of the commercially available extended release clarithromycin in a test population of 66 adult subjects under fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Clarithromycin ER 500 mg tablets; Drug: BIAXIN® XL 500 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: 66 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Randomized, Two-Way Crossover, Single-Dose, Open-Label Study to Evaluate the Relative Bioavailability of a Test Extended Release Tablet Formulation of Clarithromycin (500 mg), Compared to an Equivalent Dose of a Commercially Available Reference Drug Product (Biaxin® XL Filmtab) in 66 Fasted, Healthy, Adult Subjects
• Study Start Date: Sep 1, 2002
• Actual Primary Completion Date: Oct 1, 2002
• Actual Study Completion Date: Oct 1, 2002

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Clarithromycin (test) First	Drug: Clarithromycin ER 500 mg tablets; 1 x 500 mg
Active Comparator: Biaxin® XL (reference) First	Drug: BIAXIN® XL 500 mg tablets; 1 x 500 mg

Outcome Measures

Primary Outcome Measures

1. Cmax - Maximum Observed Concentration [Blood samples collected over 36 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 36 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 [Blood samples collected over 36 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

• Sex: Males or females who are surgically sterile or have been post-menopausal for at least 6 months; similar proportions of each preferred.

• Age: At least 18 years.

• Qualifying subjects must be in good health and physical condition as determined by medical history, complete physical examination, and laboratory tests, all obtained within four (4) weeks prior to study start. The subjects may not have a history of significant past illness expected to affect the investigation. The normal status of subjects will be confirmed by the following procedures:

1. Laboratory Tests:

Hemoglobin, hematocrit, RBC, WBC, differential count, serum electrolytes (Nz, K, Cl), fasting blood glucose, BUN, bilirubin,m creatinine, AST, ALT, LD, alkaline phosphatase and urinalysis. HIV, Hepatitis B, Hepatitis C, and drugs of abuse testing will be done for screening purposes only. Urine drugs of abuse testing will be repeated at each check-in. Female subjects will have a serum pregnancy test done at screening and a urine pregnancy test prior to each study period at check-in. Post-menopausal females will have an FSH (Follicle Stimulating Hormone) level performed to confirm post-menopausal status.

Laboratory values which are greater than ±20% of the normal range will not qualify unless specifically accepted (with comment) by the Principal Investigator. Results of HIV, Hepatitis B, Hepatitis C, and drugs of abuse must be negative or non-reactive for the subject to qualify for the study.

1. Electrocardiogram

A 12-lead electrocardiogram (ECG) will be obtained for all subjects. The original tracings, plus interpretation, will be included in the case report form packet.

• Subjects must read and sign the Consent Form.

Exclusion Criteria

• Subjects not complying with the above inclusion criteria must be excluded from the study.

• In addition, any one of the conditions listed below will exclude a subject from the study:

1. History of treatment for alcoholism, substance abuse, or drug abuse within past 24 months.

2. History of malignancy, stroke, diabetes, cardiac, renal or liver disease, or other serious illness.

3. History of treatment for any gastrointestinal disorder within the past 5 years.

4. History of treatment for asthma within the past five (5) years.

5. History of diarrhea within 24 hours prior to dosing.

6. Females who are pregnant or lactating.

7. History of hypersensitivity to clarithromycin or any macrolide antibiotic.

1. Conditions upon screening which might contraindicate or require that caution be used in the administration of dexmethylphenidate hydrochloride, including:

1. Sitting systolic blood pressure below 90 mm Hg, or diastolic pressure below 50 mm Hg.

2. Heart rate less than 50 beats per minute after a 5-minute rest in a seated position.

• Inability to read and/or sign the consent form.

• Treatment with any other investigational drug during the four (4) weeks prior to the initial dosing for this study.

• Subjects who have donated blood within four (4) weeks prior to the initial dosing for this study.

• Subjects who smoke or use tobacco products or are currently using nicotine products (patches, gums, etc.). Three (3) consecutive months abstinence is required.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gateway Medical Research	St. Charles	Missouri	United States	63301

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: Ali Ziaee, M.D., Gateway Medical Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00840411
• Other Study ID Numbers: 02197
• First Posted: Feb 10, 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® XL (Reference) First
Arm/Group Description	Clarithromycin 500 mg ER Tablet (test) dosed in first period followed by Biaxin® XL 500 mg Filmtab® (reference) dosed in second period.	Biaxin® XL 500 mg Filmtab® (reference) dosed in first period followed by Clarithromycin 500 mg ER Tablet (test) dosed in second period
Period Title: First Intervention
STARTED	33	33
COMPLETED	32	33
NOT COMPLETED	1	0
Period Title: First Intervention
STARTED	32	33
COMPLETED	31	33
NOT COMPLETED	1	0
Period Title: First Intervention
STARTED	31	33
COMPLETED	31	33
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Clarithromycin (Test) First	Biaxin® XL (Reference) First	Total
Arm/Group Description	Clarithromycin 500 mg ER Tablet (test) dosed in first period followed by Biaxin® XL 500 mg Filmtab® (reference) dosed in second period.	Biaxin® XL 500 mg Filmtab® (reference) dosed in first period followed by Clarithromycin 500 mg ER Tablet (test) dosed in second period	Total of all reporting groups
Overall Participants	33	33	66
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	32 97%	32 97%	64 97%
>=65 years	1 3%	1 3%	2 3%
Sex: Female, Male (Count of Participants)
Female	5 15.2%	6 18.2%	11 16.7%
Male	28 84.8%	27 81.8%	55 83.3%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	24 72.7%	29 87.9%	53 80.3%
Black	9 27.3%	4 12.1%	13 19.7%
Region of Enrollment (participants) [Number]
United States	33 100%	33 100%	66 100%

Outcome Measures

1. Primary Outcome

Title	Cmax - Maximum Observed Concentration
Description	Bioequivalence based on Cmax
Time Frame	Blood samples collected over 36 hour period

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Clarithromycin	Biaxin® XL
Arm/Group Description	Clarithromycin 500 mg ER Tablet (test) dosed in either period	Biaxin® XL 500 mg Filmtab® (reference) dosed in either period
Measure Participants	62	62
Mean (Standard Deviation) [ng/mL]	640.08 (214.223)	640.11 (231.752)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clarithromycin, Biaxin® XL
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Using PROC GLM procedures in SAS, analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Test/Ref Ratio of LS Means x 100
	Estimated Value	100.0
	Confidence Interval	() 90%; 93.3 to 107.1
	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 36 hour period

Outcome Measure Data

Analysis Population Description

AUCinf could not be estimated for some subjects.

Arm/Group Title	Clarithromycin	Biaxin® XL
Arm/Group Description	Clarithromycin 500 mg ER Tablet (test) dosed in either period	Biaxin® XL 500 mg Filmtab® (reference) dosed in either period
Measure Participants	62	58
Mean (Standard Deviation) [ng*h/mL]	10255.3 (4102.34)	11767.7 (5131.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clarithromycin, Biaxin® XL
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Using PROC GLM procedures in SAS, analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Least Squares Means
	Estimated Value	86.5
	Confidence Interval	() 90%; 80.1 to 93.4
	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
Description	Bioequivalence based on AUC0-t
Time Frame	Blood samples collected over 36 hour period

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Clarithromycin	Biaxin® XL
Arm/Group Description	Clarithromycin 500 mg ER Tablet (test) dosed in either period	Biaxin® XL 500 mg Filmtab® (reference) dosed in either period
Measure Participants	62	62
Mean (Standard Deviation) [ng*h/mL]	9735.5 (3813.66)	11136.6 (4412.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clarithromycin, Biaxin® XL
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Using PROC GLM procedures in SAS, analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Least Squares Means
	Estimated Value	87.2
	Confidence Interval	() 90%; 81.0 to 93.8
	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.