Clarithromycin 500 mg Extended Release Tablets Under Fasting Conditions

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Clarithromycin ER 500 mg tablets; Drug: BIAXIN® XL 500 mg tablets

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St. Charles, Missouri, United States, 63301
      • Gateway Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

  2. 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.

C. 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.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax - Maximum Observed Concentration	Bioequivalence based on Cmax	Blood samples collected over 36 hour period
AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)	Bioequivalence based on AUC0-inf	Blood samples collected over 36 hour period
AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration	Bioequivalence based on AUC0-t	Blood samples collected over 36 hour period

Collaborators and Investigators

• Sponsor: Teva Pharmaceuticals USA
• Investigators: Principal Investigator: Ali Ziaee, M.D., Gateway Medical Research

Study record dates

Study Major Dates

• Study Start: September 1, 2002
• Primary Completion (Actual): October 1, 2002
• Study Completion (Actual): October 1, 2002

Study Registration Dates

• First Submitted: February 6, 2009
• First Submitted That Met QC Criteria: February 9, 2009
• First Posted (Estimate): February 10, 2009

Study Record Updates

• Last Update Posted (Estimate): September 11, 2009
• Last Update Submitted That Met QC Criteria: September 1, 2009
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: Bioequivalence; Healthy Subjects
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Clarithromycin
• Other Study ID Numbers: 02197