Pharmacokinetics of Voriconazole in Obese Subjects

NCT01030653 | Completed Phase 4 Results

• 1 other identifier: 09010
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

Voriconazole; Pharmacokinetics; Obese; Healthy Volunteer

Outcome Measures

Primary Outcomes (2)

• Steady-State Cmax and Cmin of Two Voriconazole Dosing Regimens

  Cmax is the maximum concentration, and Cmin is the minimum concentration. These measurements are based on analysis of plasma. The units shown are milligrams of voriconazole per liter of plasma. The two dosing regimens are: 1. a loading dose (400 mg x 2 doses, day 1) and maintenance doses (200 mg every 12 hours x 7 doses) in obese subjects. 2. a loading dose (400 mg x 2 doses, day 1) and maintenance doses (300 mg every 12 hours x 7 doses) in obese subjects.

  Day 5

• Geometric Mean Ratio of the AUC Between the High and Low Dose Voriconazole

  AUC is the area under the concentration-time curve. The Geometric Mean Ratio and 90% confidence interval around this value permit an assessment of the bioequivalence of two dosing regimens in the same group. The geometric mean is computed based on the ratio of the AUC value from the high dose compared to the AUC value from the low dose for each individual. This ratio provides a more robust interpretation of the differences between the two dosing arms because each individual serves as their own control.

  14 days

Secondary Outcomes (1)

• The Area Under the Curve Over the Dosing Interval for All Participants While on the High Dose and Low Dose Interventions.

  12 hours

Study Arms (2)

Voriconazole low dose first then high dose

EXPERIMENTAL

Voriconazole administered by Mouth as a Loading Dose (400 mg x 2 Doses, Day 1) and as Maintenance Doses (200 mg Every 12 Hours x 7 Doses) followed by 7 day washout followed by Loading Dose (400 mg x 2 Doses, Day 1) and a Maintenance Doses (300 mg Every 12 Hours x 7 Doses)

Drug: Voriconazole low dose; Drug: Voriconazole high dose

Voriconazole high dose first then low dose

EXPERIMENTAL

Voriconazole administered by Mouth as a Loading Dose (400 mg x 2 Doses, Day 1) and as Maintenance Doses (300 mg Every 12 Hours x 7 Doses) followed by 7 day washout followed by Loading Dose (400 mg x 2 Doses, Day 1) and a Maintenance Doses (200 mg Every 12 Hours x 7 Doses)

Drug: Voriconazole low dose; Drug: Voriconazole high dose

Interventions

Voriconazole low dose DRUG

Voriconazole 400 mg po x 2 doses (loading dose)then 200 mg po twice daily x 7 doses

Also known as: Vfend

Voriconazole high dose first then low dose; Voriconazole low dose first then high dose

Voriconazole high dose DRUG

Voriconazole 400 mg po x 2 doses (loading dose)then 300 mg po twice daily x 7 doses

Also known as: Vfend

Voriconazole high dose first then low dose; Voriconazole low dose first then high dose

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• males and females, 18 to 50 years of age;
• non-smoking or light-smoking (≤5 cigarettes per day) volunteers;
• BMI ≥ 35 kg/m2;
• 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.

You may not qualify if:

• History of significant hypersensitivity reaction or intolerance to voriconazole, fluconazole,itraconazole, posaconazole, or ketoconazole ;
• history of significant clinical illness requiring pharmacological management;
• abnormal serum electrolyte or complete blood count requiring further clinical work-up;
• transaminases (AST or ALT) \>2.5 x upper limit of normal;
• estimated creatinine clearance \<50 mL/min (Cockcroft-Gault equation);
• positive urine pregnancy test (if female);
• abnormal electrocardiogram (ECG) as judged by study physician;
• unable to tolerate venipuncture and multiple blood draws;
• clinically significant abnormal physical examination defined as a physical finding requiring further clinical work-up.

Sponsors & Collaborators

• Manjunath Prakash Pai: lead
• TKL Research, Inc.: collaborator
• Pfizer: collaborator

Study Sites (1)

TKL Research Inc

Paramus, New Jersey, 07652, United States

Location

Related Publications (1)

• Pai MP, Norenberg JP, Anderson T, Goade DW, Rodvold KA, Telepak RA, Mercier RC. Influence of morbid obesity on the single-dose pharmacokinetics of daptomycin. Antimicrob Agents Chemother. 2007 Aug;51(8):2741-7. doi: 10.1128/AAC.00059-07. Epub 2007 Jun 4.

  PMID: 17548489 BACKGROUND

MeSH Terms

Conditions

Obesity

Interventions

Voriconazole

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The study sample size was small.

Results Point of Contact

• Title: Manjuanth Pai
• Organization: University of Michigan

amitpai@med.umich.edu

7346470006

Study Officials

• Manjunath P Pai, PharmD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 10, 2009
• First Posted: December 11, 2009
• Study Start: November 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: May 1, 2010
• Last Updated: February 9, 2017
• Results First Posted: February 9, 2017

Record last verified: 2016-12

Locations

US (1)