Azithromycin 600 Mg Tablets, Fasting
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 36 adult subjects under fasting conditions.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
Detailed Description
Criteria for Evaluation: FDA Bioequivalence Criteria
Statistical Methods: FDA bioequivalence statistical methods
Study Design
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 fasting
|
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 fasting
|
Outcome Measures
Primary Outcome Measures
- Cmax - Maximum Observed Concentration - Azithromycin in Plasma [Blood samples collected over 168 hour period]
Bioequivalence based on Cmax
- 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
- AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of the Last Non-zero Concentration (Per Participant) - Azithromycin in Plasma [Blood samples collected over 168 hour period]
Bioequivalence based on AUC0-t
Eligibility Criteria
Criteria
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: Steven Herrmann, M.D., Cetero Research, San Antonio
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 02183
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
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 | 18 | 18 |
COMPLETED | 17 | 18 |
NOT COMPLETED | 1 | 0 |
Period Title: First Intervention | ||
STARTED | 17 | 18 |
COMPLETED | 16 | 18 |
NOT COMPLETED | 1 | 0 |
Period Title: First Intervention | ||
STARTED | 16 | 18 |
COMPLETED | 16 | 18 |
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 | 18 | 18 | 36 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
18
100%
|
18
100%
|
36
100%
|
>=65 years |
0
0%
|
0
0%
|
0
0%
|
Sex: Female, Male (Count of Participants) | |||
Female |
10
55.6%
|
10
55.6%
|
20
55.6%
|
Male |
8
44.4%
|
8
44.4%
|
16
44.4%
|
Race/Ethnicity, Customized (Number) [Number] | |||
Caucasian |
15
83.3%
|
16
88.9%
|
31
86.1%
|
Black |
2
11.1%
|
1
5.6%
|
3
8.3%
|
Asian |
1
5.6%
|
1
5.6%
|
2
5.6%
|
Region of Enrollment (participants) [Number] | |||
United States |
18
100%
|
18
100%
|
36
100%
|
Outcome Measures
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 | 34 | 34 |
Mean (Standard Deviation) [ng/mL] |
522.255
(170.503)
|
544.024
(159.688)
|
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 | 96.00 | |
Confidence Interval |
() 90% 87.96 to 104.78 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Bioequivalence is established when 90% Confidence Interval falls within 80 - 125 |
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 | 34 | 34 |
Mean (Standard Deviation) [ng*h/mL] |
6894.151
(1715.464)
|
6989.682
(2101.213)
|
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 | 98.63 | |
Confidence Interval |
() 90% 92.34 to 105.35 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Bioequivalence is established when 90% Confidence Interval falls within 80 - 125 |
Title | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of the 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 | 34 | 34 |
Mean (Standard Deviation) [ng*h/mL] |
6190.268
(1501.185)
|
6167.730
(1800.711)
|
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 | 100.37 | |
Confidence Interval |
() 90% 93.95 to 107.21 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Bioequivalence is established when 90% Confidence Interval falls within 80 - 125 |
Adverse Events
Limitations/Caveats
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.
Results Point of Contact
Name/Title | Manager, Biopharmaceutics |
---|---|
Organization | Teva Pharmaceuticals USA |
Phone | 1-866-384-5525 |
clinicaltrialqueries@tevausa.com |
- 02183