A Relative Bioavailability Study of 200mg/5 mL Azithromycin Oral Suspension Under Non-Fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00830336
• Collaborator: (none)
• Enrollment: 80
• Location: 1
• Arms: 2
• Duration (Months): 1
• Patients Per Site Per Month: 78.5

Study Details

Study Description

Brief Summary

The study will compare the relative bioavailability (rate and extent of absorption) of 200 mg/5 mL Azithromycin oral suspension manufactured by TEVA Pharmaceutical Industries Ltd.; distributed by TEVA Pharmaceuticals USA with that of 200 mg/5 mL ZITHROMAX oral suspension distributed by Pfizer labs, a division of Pfizer Inc. following a single oral 10 mL dose (400 mg) in healthy adult subjects administered under non-fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Azithromycin; Drug: Zithromax®	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: 80 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Relative Bioavailability Study of 200mg/5 mL Azithromycin Oral Suspension Under Non-Fasting Conditions
• Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Nov 1, 2005
• Actual Study Completion Date: Nov 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Azithromycin (test) Azithromycin for Oral Suspension 200 mg/5 mL (test) dosed in first period followed by Zithromax® Oral Suspension 200 mg/5 mL (reference) dosed in second period	Drug: Azithromycin; Oral Suspension
Active Comparator: Zithromax® (reference) Zithromax® for Oral Suspension 200 mg/5 mL (reference) dosed in first period followed by Azithromycin for Oral Suspension 200 mg/5 mL (test) dosed in second period	Drug: Zithromax®; Oral Suspension; Other Names: Zithromax® for Oral Suspension

Outcome Measures

Primary Outcome Measures

1. Cmax - Maximum Observed Concentration [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) [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) [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

• Screening Demographics: All subjects selected for this study will be healthy men and women 18 years of age or older at the time of dosing. The subject's body mass index (BMI) should be between 19 and 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 GB 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)

• If female and:

• Of childbearing potential, is practicing an acceptable method of birth control for the duration of the study as judged by the investigator(s), such as condom with spermicide, diaphragm with spermicide, intrauterine device (IUD), or abstinence; or

• 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 demonstrating a reactive screen for hepatitis B surface antigen, hepatitis C antibody or HIV antibody.

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

• Female subjects demonstrating a positive pregnancy screen.

• Female subjects who are currently breastfeeding.

• Subjects with a history of allergic response(s) to azithromycin 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 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 28 days prior to Period I dosing. All subjects will be 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 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.

• Female subjects who report using implanted or injected hormonal contraceptives (birth control) during the 6 months prior to Period I dosing.

• Female subjects who report using oral hormonal contraceptives (birth control) during the 14 days prior to Period I dosing.

• Subjects who report having difficulty fasting or consuming standardized meals.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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: NCT00830336
• Other Study ID Numbers: R05-1375
• 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: Azithromycin

Study Results

Participant Flow

Arm/Group Title	Azithromycin (Test) First	Zithromax® (Reference) First
Arm/Group Description	Azithromycin for Oral Suspension 200 mg/5 mL (test) dosed in first period followed by Zithromax® Oral Suspension 200 mg/5 mL (reference) dosed in second period	Zithromax® for Oral Suspension 200 mg/5 mL (reference) dosed in first period followed by Azithromycin for Oral Suspension 200 mg/5 mL (test) dosed in second period
Period Title: First Intervention
STARTED	40	40
COMPLETED	40	40
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	40	40
COMPLETED	39	40
NOT COMPLETED	1	0
Period Title: First Intervention
STARTED	39	40
COMPLETED	39	40
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Azithromycin (Test) First	Zithromax® (Reference) First	Total
Arm/Group Description	Azithromycin for Oral Suspension 200 mg/5 mL (test) dosed in first period followed by Zithromax® Oral Suspension 200 mg/5 mL (reference) dosed in second period	Zithromax® for Oral Suspension 200 mg/5 mL (reference) dosed in first period followed by Azithromycin for Oral Suspension 200 mg/5 mL (test) dosed in second period	Total of all reporting groups
Overall Participants	40	40	80
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	39 97.5%	39 97.5%	78 97.5%
>=65 years	1 2.5%	1 2.5%	2 2.5%
Sex: Female, Male (Count of Participants)
Female	19 47.5%	25 62.5%	44 55%
Male	21 52.5%	15 37.5%	36 45%
Race/Ethnicity, Customized (Number) [Number]
White	37 92.5%	37 92.5%	74 92.5%
Black	1 2.5%	0 0%	1 1.3%
Asian	1 2.5%	1 2.5%	2 2.5%
Native American	0 0%	2 5%	2 2.5%
Pacific Islander/Hawaiian	1 2.5%	0 0%	1 1.3%
Region of Enrollment (participants) [Number]
United States	40 100%	40 100%	80 100%

Outcome Measures

1. Primary Outcome

Title	Cmax - Maximum Observed Concentration
Description	Bioequivalence based on Cmax
Time Frame	Blood samples collected over 168 hour period

Outcome Measure Data

Analysis Population Description

Samples for two subjects who completed the study were not analyzed per protocol due to emesis during the sample collection period.

Arm/Group Title	Azithromycin	Zithromax®
Arm/Group Description	Azithromycin for Oral Suspension 200 mg/5 mL (test) dosed in either period	Zithromax® for Oral Suspension 200 mg/5 mL (reference) dosed in either period
Measure Participants	77	77
Mean (Standard Deviation) [ng/mL]	560.56 (212.71)	562.97 (254.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin, Zithromax®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The pharmacokinetic parameters were 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	Geometric Test/Ref Ratio x 100
	Estimated Value	103.08
	Confidence Interval	() 90%; 95.41 to 111.37
	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 168 hour period

Outcome Measure Data

Analysis Population Description

Samples for two subjects who completed the study were not analyzed per protocol due to emesis during the sample collection period.

Arm/Group Title	Azithromycin	Zithromax®
Arm/Group Description	Azithromycin for Oral Suspension 200 mg/5 mL (test) dosed in either period	Zithromax® for Oral Suspension 200 mg/5 mL (reference) dosed in either period
Measure Participants	77	77
Mean (Standard Deviation) [ng*h/mL]	5140.47 (1630.93)	4884.55 (1599.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin, Zithromax®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The pharmacokinetic parameters were 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	Geometric Test/Ref Ratio x 100
	Estimated Value	105.84
	Confidence Interval	() 90%; 99.33 to 112.77
	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 168 hour period

Outcome Measure Data

Analysis Population Description

Samples for two subjects who completed the study were not analyzed per protocol due to emesis during the sample collection period.

Arm/Group Title	Azithromycin	Zithromax®
Arm/Group Description	Azithromycin for Oral Suspension 200 mg/5 mL (test) dosed in either period	Zithromax® for Oral Suspension 200 mg/5 mL (reference) dosed in either period
Measure Participants	77	77
Mean (Standard Deviation) [ng*h/mL]	4555.91 (1502.93)	4277.83 (1431.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin, Zithromax®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The pharmacokinetic parameters were 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	Geometric Test/Ref Ratio x 100
	Estimated Value	107.04
	Confidence Interval	() 90%; 99.96 to 114.62
	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.