Pharmacokinetics (PK) Study of a Fluconazole Loading Dose in Infants and Toddlers

Candidiasis Clinical Trial

Official title:

Pharmacokinetics of a Fluconazole Loading Dose in Infants and Toddlers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00797420
• Other study ID #: Pro00011454
• Secondary ID: NIH-5U10-HD-0459
• Status: Completed
• Phase: Phase 1
• Start date: November 2008
• Est. completion date: September 2011

Study information

• Verified date: November 2018
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the pharmacokinetics and safety of a fluconazole loading dose in infants and toddlers.

Description:

This is an open label study to investigative the pharmacokinetics and safety of a fluconazole loading dose in infants and toddlers < 2 years of age with suspected sepsis. There will be two treatment groups: single fluconazole loading dose 25 mg/kg; fluconazole loading dose 25mg/kg followed by 12 mg/kg daily for total of 5 days. There will be three age cohorts within each group: pre-term < 30 week EGA infants > 48 hours and < 31 days; > 30 weeks EGA infants > 48 hours and < 31 days; infants ≥ 31 days and < 2 years of age. The study requires administration of fluconazole over 1-5 days depending on treatment group followed by 1 week of safety monitoring. Six to eight 100 µL PK samples will be obtained over the 5 days of drug administration. The risks are reasonable vs. the benefits and have been minimized appropriately. There may be benefit to the subjects (administration of empirical antifungal therapy), and information from the study may benefit a large number of other infants and toddlers with suspected or proven fungal sepsis. There is a data analysis plan.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: September 2011
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 2 Years

Eligibility

Inclusion Criteria:

• suspected sepsis with blood culture within 48 hours

• age = 48 hours and < 2 years of age

• sufficient venous access to permit study drug administration

Exclusion Criteria:

• allergic reaction to azole

• history of fluconazole administration in prior 5 days

• liver dysfunction

• renal failure

• concomitant use of cyclosporine, tacrolimus, or azithromycin

Related Conditions & MeSH terms

• Candidiasis

Intervention

Drug:
• Fluconazole Loading Dose
Single Fluconazole loading dose 25 mg/kg
• Fluconazole Loading Dose & High Dose
Fluconazole loading dose 25 mg/kg, followed by fluconazole 12 mg/kg q24 hours for total of 5 days

Locations

Country	Name	City	State
United States	Duke Univeristy Medical Center	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Daniel Benjamin	Pediatric Pharmacology Research Units Network

Country where clinical trial is conducted

United States, 

References & Publications (7)

Anaissie EJ, Kontoyiannis DP, Huls C, Vartivarian SE, Karl C, Prince RA, Bosso J, Bodey GP. Safety, plasma concentrations, and efficacy of high-dose fluconazole in invasive mold infections. J Infect Dis. 1995 Aug;172(2):599-602. — View Citation

Benjamin DK Jr, DeLong ER, Steinbach WJ, Cotton CM, Walsh TJ, Clark RH. Empirical therapy for neonatal candidemia in very low birth weight infants. Pediatrics. 2003 Sep;112(3 Pt 1):543-7. — View Citation

Benjamin DK Jr, Stoll BJ. Infection in late preterm infants. Clin Perinatol. 2006 Dec;33(4):871-82; abstract x. Review. — View Citation

Brammer KW, Coates PE. Pharmacokinetics of fluconazole in pediatric patients. Eur J Clin Microbiol Infect Dis. 1994 Apr;13(4):325-9. — View Citation

Novelli V, Holzel H. Safety and tolerability of fluconazole in children. Antimicrob Agents Chemother. 1999 Aug;43(8):1955-60. — View Citation

Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, Lemons JA, Donovan EF, Stark AR, Tyson JE, Oh W, Bauer CR, Korones SB, Shankaran S, Laptook AR, Stevenson DK, Papile LA, Poole WK. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics. 2002 Aug;110(2 Pt 1):285-91. — View Citation

Wade KC, Wu D, Kaufman DA, Ward RM, Benjamin DK Jr, Sullivan JE, Ramey N, Jayaraman B, Hoppu K, Adamson PC, Gastonguay MR, Barrett JS; National Institute of Child Health and Development Pediatric Pharmacology Research Unit Network. Population pharmacokinetics of fluconazole in young infants. Antimicrob Agents Chemother. 2008 Nov;52(11):4043-9. doi: 10.1128/AAC.00569-08. Epub 2008 Sep 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma concentration of Fluconazole		6-8 samples over 5 days