Pharmacokinetics of Voriconazole in Obese Subjects

This study has been completed.
Sponsor:
Collaborator:
TKL Research, Inc.
Information provided by:
Albany College of Pharmacy and Health Sciences
ClinicalTrials.gov Identifier:
NCT01030653
First received: December 10, 2009
Last updated: May 12, 2010
Last verified: May 2010
  Purpose

Obese subjects may require a higher fixed oral maintenance dosing regimen of voriconazole compared to normal weight subjects to achieve comparable plasma exposures. The current study is designed to address this issue.


Condition Intervention Phase
Healthy
Drug: Voriconazole
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Health Services Research
Official Title: Pharmacokinetics of Voriconazole in Obese Subjects

Resource links provided by NLM:


Further study details as provided by Albany College of Pharmacy and Health Sciences:

Primary Outcome Measures:
  • To compare the steady-state pharmacokinetics of voriconazole administered by mouth as a loading dose (400 mg x 2 doses, day 1) and as two fixed maintenance doses (200 mg or 300 mg every 12 hours x 7 doses) in obese subjects. [ Time Frame: Day 5 ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: November 2009
Study Completion Date: May 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Voriconazole Drug: Voriconazole
Voriconazole 400 mg po x 2 doses (loading dose)then 200 mg po twice daily x 7 doses Voriconazole 400 mg po x 2 doses (loading dose)then 300 mg po twice daily x 7 doses
Other Name: Vfend

Detailed Description:

The prevalence of obesity has increased tremendously in the past two decades. An estimated 1 out of 5 persons in the United States are classified as obese. Under representation of obese patients in pharmacokinetic trials grossly limit generalizability of drug dosing recommendations in this emerging population. No published pharmacokinetic studies of voriconazole dosing in patients with obesity currently exist in the literature. Specifically,voriconazole pharmacokinetic data from subjects with a body mass index (BMI) ≥ 35 kg/m2(Class II and III obesity) are limited.

Voriconazole is available as both an intravenous and oral formulation. Anecdotal experience suggest that the use of oral voriconazole to be significantly more prevalent that that of intravenous therapy. The current oral recommended dosing regimen for voriconazole includes use of 200 mg every 12 hours for patients who are over 40 kg. The dosage can be increased to 300 mg by mouth every 12 hours in situations where a sufficient clinical response is not noted. A weight based dosing strategy is also utilized in patients with more serious infections (3-6 mg/kg IV Q 12 hours) such as invasive aspergillosis. Voriconazole demonstrates non-linear pharmacokinetics and so dosing based on total body weight may result in non-dose proportional exposure. For example, a 1.5 fold dose increment in voriconazole from 200 mg to 300 mg every 12 hours results in a 2.5 fold increase in exposure. The most appropriate body size descriptor is unknown (i.e. ideal body weight, fat free weight, lean body weight, etc.) for most antimicrobials, including voriconazole. As a consequence, the appropriateness of weight-based voriconazole dosage selection in obese patients is not known. Intuitively, weight based dosing (on total body weight) in this population could lead to higher than expected exposures (non-linear pharmacokinetics) and lead to potential adverse events. Therapeutic drug monitoring is increasingly advocated as a system to improve voriconazole dosing. However, an assay to measure voriconazole concentrations in the clinic is not routinely available. Hence, the current pilot study proposes to characterize the pharmacokinetic profile of voriconazole in obese subjects using two fixed dose regimens.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. males and females, 18 to 50 years of age;
  2. non-smoking or light-smoking (≤5 cigarettes per day) volunteers;
  3. BMI ≥ 35 kg/m2;
  4. female subjects of childbearing potential either surgically sterilized, using an effective method of contraception (diaphragm, cervical cap, condom) or agree to abstain from sex from time of prestudy screening, during entire study period and 1 week following the study period.

Exclusion Criteria:

  1. History of significant hypersensitivity reaction or intolerance to voriconazole, fluconazole,itraconazole, posaconazole, or ketoconazole ;
  2. history of significant clinical illness requiring pharmacological management;
  3. abnormal serum electrolyte or complete blood count requiring further clinical work-up;
  4. transaminases (AST or ALT) >2.5 x upper limit of normal;
  5. estimated creatinine clearance <50 mL/min (Cockcroft-Gault equation);
  6. positive urine pregnancy test (if female);
  7. abnormal electrocardiogram (ECG) as judged by study physician;
  8. unable to tolerate venipuncture and multiple blood draws;
  9. clinically significant abnormal physical examination defined as a physical finding requiring further clinical work-up.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01030653

Locations
United States, New Jersey
TKL Research Inc
Paramus, New Jersey, United States, 07652
Sponsors and Collaborators
Albany College of Pharmacy and Health Sciences
TKL Research, Inc.
Investigators
Principal Investigator: Manjunath P Pai, PharmD Albany College of Pharmacy and Health Sciences
  More Information

Publications:
Responsible Party: Manjunath (Amit) P. Pai, PharmD, Associate Professor, Albany College of Pharmacy and Health Sciences
ClinicalTrials.gov Identifier: NCT01030653     History of Changes
Other Study ID Numbers: 09010
Study First Received: December 10, 2009
Last Updated: May 12, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Albany College of Pharmacy and Health Sciences:
Voriconazole
Pharmacokinetics
Obese
Healthy Volunteer

Additional relevant MeSH terms:
Voriconazole
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 27, 2014