Clarithromycin 500 mg Extended Release Tablets Under Non-Fasting Conditions.
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 22 adult subjects under fed 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: 1
|
Drug: Clarithromycin ER 500 mg tablets
1 x 500 mg
|
Active Comparator: 2
|
Drug: BIAXIN® XL 500 mg tablets
1 x 500 mg
|
Outcome Measures
Primary Outcome Measures
- Cmax - Maximum Observed Concentration [Blood samples collected over 36 hour period]
Bioequivalence based on Cmax
- 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
- 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
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:
- 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.
- 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 any gastrointestinal disorder within the past 5 years.
-
History of treatment for asthma within the past five (5) years.
-
History of diarrhea within 24 hours prior to dosing.
-
Females who are pregnant or lactating.
-
History of hypersensitivity to clarithromycin or any macrolide antibiotic.
- Conditions upon screening which might contraindicate or require that caution be used in the administration of dexmethylphenidate hydrochloride, including:
-
Sitting systolic blood pressure below 90 mm Hg, or diastolic pressure below 50 mm Hg.
-
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 Inc. | St. Charles | Missouri | United States | 63301 |
Sponsors and Collaborators
- Teva Pharmaceuticals USA
Investigators
- Principal Investigator: Ali Ziaee, MD, Gateway Medical Research
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 02198
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Clarithromycin (Test) First | Biaxin® (Reference) First |
---|---|---|
Arm/Group Description | Clarithromycin 500 mg ER Tablets (test) dosed in first period followed by Biaxin® XL Filmtab® 500 mg (reference) dosed in second period | Biaxin® XL Filmtab® 500 mg (reference) dosed in first period followed by Clarithromycin 500 mg Tablet (test) dosed in second period. |
Period Title: First Intervention | ||
STARTED | 11 | 11 |
COMPLETED | 11 | 11 |
NOT COMPLETED | 0 | 0 |
Period Title: First Intervention | ||
STARTED | 11 | 11 |
COMPLETED | 10 | 11 |
NOT COMPLETED | 1 | 0 |
Period Title: First Intervention | ||
STARTED | 10 | 11 |
COMPLETED | 10 | 11 |
NOT COMPLETED | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Clarithromycin (Test) First | Biaxin® (Reference) First | Total |
---|---|---|---|
Arm/Group Description | Clarithromycin 500 mg ER Tablets (test) dosed in first period followed by Biaxin® XL Filmtab® 500 mg (reference) dosed in second period | Biaxin® XL Filmtab® 500 mg (reference) dosed in first period followed by Clarithromycin 500 mg Tablet (test) dosed in second period. | Total of all reporting groups |
Overall Participants | 11 | 11 | 22 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
10
90.9%
|
10
90.9%
|
20
90.9%
|
>=65 years |
1
9.1%
|
1
9.1%
|
2
9.1%
|
Sex: Female, Male (Count of Participants) | |||
Female |
5
45.5%
|
6
54.5%
|
11
50%
|
Male |
6
54.5%
|
5
45.5%
|
11
50%
|
Race/Ethnicity, Customized (Number) [Number] | |||
Caucasian |
9
81.8%
|
10
90.9%
|
19
86.4%
|
Black |
2
18.2%
|
1
9.1%
|
3
13.6%
|
Region of Enrollment (participants) [Number] | |||
United States |
11
100%
|
11
100%
|
22
100%
|
Outcome Measures
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® |
---|---|---|
Arm/Group Description | Clarithromycin 500 mg ER Tablets (test) dosed in either period | Biaxin® XL Filmtab® 500 mg (reference) dosed in either period |
Measure Participants | 21 | 21 |
Mean (Standard Deviation) [ng/mL] |
1515.00
(533.782)
|
1464.10
(700.030)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Clarithromycin, Biaxin® |
---|---|---|
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 | 106.9 | |
Confidence Interval |
() 90% to |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Bioequivalence is established when the ratio of the mean falls within 80-125. |
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 |
---|
Data from subjects who completed the study were included in the statistical analysis. |
Arm/Group Title | Clarithromycin | Biaxin® |
---|---|---|
Arm/Group Description | Clarithromycin 500 mg ER Tablets (test) dosed in either period | Biaxin® XL Filmtab® 500 mg (reference) dosed in either period |
Measure Participants | 21 | 21 |
Mean (Standard Deviation) [ng*h/mL] |
14449.3
(4684.11)
|
15699.8
(5991.11)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Clarithromycin, Biaxin® |
---|---|---|
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 | 92.7 | |
Confidence Interval |
() 90% to |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Bioequivalence is established when ratio of the mean falls within 80-125. |
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® |
---|---|---|
Arm/Group Description | Clarithromycin 500 mg ER Tablets (test) dosed in either period | Biaxin® XL Filmtab® 500 mg (reference) dosed in either period |
Measure Participants | 21 | 21 |
Mean (Standard Deviation) [ng*h/mL] |
14236.7
(4681.28)
|
15389.5
(5923.27)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Clarithromycin, Biaxin® |
---|---|---|
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 | 93.0 | |
Confidence Interval |
() 90% to |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Bioequivalence is established when ratio of the mean 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 |
- 02198