Comparative Effects of Azithromycin, Telithromycin and Levofloxacin on Drug Metabolizing Enzymes

This study has been completed.
Sponsor:
Collaborator:
PriCara, Unit of Ortho-McNeil, Inc.
Information provided by:
Bassett Healthcare
ClinicalTrials.gov Identifier:
NCT00164112
First received: September 9, 2005
Last updated: September 13, 2005
Last verified: March 2005
  Purpose

Studies have previously shown that a broad drug interaction screening can be performed using enzyme specific probes such as oral caffeine for CYP1A2, N-acetyltrasferase-2 (NAT-2), and xanthine oxidase (XO), warfarin plus vitamin K for CYP2C9, omeprazole for CYP 2C19, dextromethorphan for CYP2D6, and midazolam for CYP3A4/5. This combination of probes has been validated in the Cooperstown 5+1 Cocktail (5+1).1 The use of the 5+1 cocktail provides information on the drug metabolizing enzymes that metabolize 90% of hepatically eliminated drugs for a fraction of the costs of the individual studies. Using a cocktail of biomarkers reduces the overall cost of drug interaction screening. The purpose of this study is to evaluate the effects of three Food and Drug Administration (FDA) approved oral antibiotics (azithromycin, telithromycin, and levofloxacin) on metabolism of other medications when taken together. This will be determined by the measuring the activity of drug metabolizing enzymes following administration of certain drug probes (caffeine, dextromethorphan, omeprazole, midazolam, and warfarin with vitamin K). A total of 16 subjects will complete four phases of the study: 1) Cooperstown 5+1 alone, 2) Azithromycin plus Cooperstown 5+1, 3) Telithromycin plus Cooperstown 5+1, and 4) Levofloxacin plus Cooperstown 5+1.


Condition Intervention Phase
Healthy
Drug: Cooperstown 5+1 alone
Drug: Azithromycin plus Cooperstown 5+1
Drug: Telithromycin plus Cooperstown 5+1
Drug: Levofloxacin plus Cooperstown 5+1
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Comparison of the Effect of Azithromycin, Telithromycin and Levofloxacin on Drug Metabolizing Enzymes Using the Validated Cooperstown 5+1 Cocktail

Resource links provided by NLM:


Further study details as provided by Bassett Healthcare:

Primary Outcome Measures:
  • Phenotype measures

Estimated Enrollment: 16
Study Start Date: November 2004
Estimated Study Completion Date: June 2005
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy adults between the ages of 18 and 55 years.
  • Ability to provide written informed consent.
  • Willing to avoid all medications (other than the study drugs) which may inhibit or induce hepatic microsomal enzymes during the study period. This includes prescription and non-prescription medications, vitamins, herbal supplements, and nutriceuticals.
  • Willing to avoid drinking more than the equivalence of one beer per day (one 12 ounce beer or equivalent alcohol intake) throughout the study period.
  • Women of child-bearing potential who are willing to practice non-hormonal methods of contraception during all study phases.
  • Willing to adhere to dietary restrictions as required during the study.

Exclusion Criteria:

  • Clinically significant abnormal findings by history, physical exam, ECG, or laboratory testing.
  • Elevated liver function tests twice above the upper limit of the normal range (males AST 0-50 U/L, ALT 0-60 U/L, GGT 11-50; females AST 0-40 U/L, ALT 0-50 U/L, GGT 7-32), or total bilirubin >1.3mg/dL.
  • Baseline INR >1.2.
  • Serum creatinine above the normal ranges
  • Women who are pregnant, breastfeeding, and/or not using an acceptable form of non-hormonal contraception (barrier method or abstinence) during the study.
  • History of gastrointestinal bleeding or peptic ulcer disease.
  • Any condition that may affect drug absorption (e.g., gastrectomy, malabsorption syndromes).
  • History of known hypersensitivity or serious adverse reaction to azithromycin, telithromycin, levofloxacin, midazolam, dextromethorphan, caffeine, omeprazole, heparin, warfarin, or vitamin K.
  • Poor IV access as determined by an investigator.
  • Current illicit drug use.
  • History of tobacco use within 3 months of screening.
  • Use of any drug known to inhibit or induce hepatic enzymes within 30 days of the first study phase.
  • Regular alcohol intake exceeding 1 drink/day (1 drink = 5 ounces of wine or 12 ounces of beer or 1 ounce of hard liquor) within 1 months of screening.
  • Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study drug.
  • Presence of any condition that the investigator feels would interfere with successful completion of the study.
  • Poor metabolizers of CYP2D6, CYP2C9, and CYP2C19.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00164112

Sponsors and Collaborators
Bassett Healthcare
PriCara, Unit of Ortho-McNeil, Inc.
Investigators
Principal Investigator: Joseph S Bertino, Pharm.D. Bassett Healthcare
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00164112     History of Changes
Other Study ID Numbers: CAPSS-273
Study First Received: September 9, 2005
Last Updated: September 13, 2005
Health Authority: United States: Institutional Review Board

Keywords provided by Bassett Healthcare:
Cooperstown Cocktail
Drug Metabolizing Enzymes
Drug Interactions
Phenotyping

Additional relevant MeSH terms:
Ofloxacin
Azithromycin
Telithromycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Renal Agents

ClinicalTrials.gov processed this record on July 26, 2014