Azithromycin 600 Mg Tablets, Fed

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00834132
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 1
• Patients Per Site Per Month: 23.6

Study Details

Study Description

Brief Summary

The objective of this randomized, single-dose, two-way crossover evaluation is to compare the relative bioequivalence of a test azithromycin formulation (TEVA Pharmaceuticals USA) to an equivalent oral dose of the commercially available azithromycin (Zithromax®, Pfizer, Inc.) in a test population of 24 adult subjects under fed conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Azithromycin 600 mg Tablet; Drug: Zithromax® 600 mg Tablet	Phase 1

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 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 Tablet Formulation of Azithromycin (600 mg), Compared to an Equivalent Dose of a Commercially Available Reference Drug Product (Zithromax®, Pfizer, Inc.) in 24 Fed, Healthy, Adult Subjects
• Study Start Date: Jul 1, 2002
• Actual Primary Completion Date: Aug 1, 2002
• Actual Study Completion Date: Aug 1, 2002

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Azithromycin Azithromycin 600 mg tablet (test) dosed in first period followed by Zithromax® 600 mg tablet (reference) dosed in second period	Drug: Azithromycin 600 mg Tablet; 1 x 600mg, single-dose fed
Active Comparator: Zithromax® Zithromax® 600 mg tablet (reference) dosed in first period followed by Azithromycin 600 mg tablet (test) dosed in second period	Drug: Zithromax® 600 mg Tablet; 1 x 600mg, single-dose fed

Outcome Measures

Primary Outcome Measures

1. Cmax - Maximum Observed Concentration - Azithromycin in Plasma [Blood samples collected over 168 hour period]

   Bioequivalence based on Cmax

2. AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) - Azithromycin in Plasma [Blood samples collected over 168 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)- Azithromycin in Plasma [Blood samples collected over 168 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:Non-smoking Male or Female; similar proportions of each preferred.

• Age: At least 18 years.

• Weight: BMI less than 30.

• 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 subject 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:

• Laboratory Tests: hemoglobin, hematocrit, RBC, WBC, differential count, serum electrolytes (Na, K, Cl), fasting blood glucose, BUN, bilirubin, 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. 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.

• 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:

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

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

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

• History of treatment for any gastrointestinal disorder within the past five (5) years.

• History of hepatic function impairment.

• Females who are pregnant or lactating.

• History of hypersensitivity to azithromycin, erythromycin, or any macrolide antibacterial agent.

• Conditions upon screening which might contraindicate or require that caution be used in the administration of azithromycin, including:

• Sitting systolic blood pressure below 90 mmHg, or diastolic pressure below 50 mmHg.

• 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.) At least three (4) consecutive months of abstinence is required.

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: Azber Ansar, M.D., Cetero Research, San Antonio

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00834132
• Other Study ID Numbers: 02184
• First Posted: Feb 3, 2009
• Last Update Posted: Sep 15, 2009
• Last Verified: Sep 1, 2009

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

Study Results

Participant Flow

Arm/Group Title	Azithromycin (Test) First	Zithromax® (Reference) First
Arm/Group Description	Azithromycin 600 mg tablet (test) dosed in first period followed by Zithromax® 600 mg tablet (reference) dosed in second period	Zithromax® 600 mg tablet (reference) dosed in first period followed by Azithromycin 600 mg tablet (test) dosed in second period
Period Title: First Intervention
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Azithromycin (Test) First	Zithromax® (Reference) First	Total
Arm/Group Description	Azithromycin 600 mg tablet (test) dosed in first period followed by Zithromax® 600 mg tablet (reference) dosed in second period	Zithromax® 600 mg tablet (reference) dosed in first period followed by Azithromycin 600 mg tablet (test) dosed in second period	Total of all reporting groups
Overall Participants	12	12	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	12 100%	24 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	4 33.3%	5 41.7%	9 37.5%
Male	8 66.7%	7 58.3%	15 62.5%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	7 58.3%	9 75%	16 66.7%
Black	5 41.7%	3 25%	8 33.3%
Region of Enrollment (participants) [Number]
United States	12 100%	12 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Cmax - Maximum Observed Concentration - Azithromycin in Plasma
Description	Bioequivalence based on Cmax
Time Frame	Blood samples collected over 168 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	Azithromycin	Zithromax®
Arm/Group Description	Azithromycin 600 mg tablet (test) dosed in either period	Zithromax® 600 mg tablet (reference) dosed in either period
Measure Participants	24	24
Mean (Standard Deviation) [ng/mL]	561.556 (199.349)	592.311 (255.261)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin, Zithromax®
	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	94.81
	Confidence Interval	() 90%; 84.77 to 106.04
	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) - Azithromycin in Plasma
Description	Bioequivalence based on AUC0-inf
Time Frame	Blood samples collected over 168 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	Azithromycin	Zithromax®
Arm/Group Description	Azithromycin 600 mg tablet (test) dosed in either period	Zithromax® 600 mg tablet (reference) dosed in either period
Measure Participants	24	24
Mean (Standard Deviation) [ng*h/mL]	7025.920 (1583.546)	6964.092 (1621.163)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin, Zithromax®
	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	100.89
	Confidence Interval	() 90%; 96.00 to 106.03
	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)- Azithromycin in Plasma
Description	Bioequivalence based on AUC0-t
Time Frame	Blood samples collected over 168 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	Azithromycin	Zithromax®
Arm/Group Description	Azithromycin 600 mg tablet (test) dosed in either period	Zithromax® 600 mg tablet (reference) dosed in either period
Measure Participants	24	24
Mean (Standard Deviation) [ng*h/mL]	6132.710 (1483.937)	6063.795 (1436.447)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin, Zithromax®
	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	101.14
	Confidence Interval	() 90%; 96.05 to 106.49
	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.