Voriconazole Pharmacokinetics in Children With Gastrointestinal Graft Versus Host Disease

• ClinicalTrials.gov Identifier: NCT00792246
• Recruitment Status: Completed
• First Posted: November 17, 2008
• Last Update Posted: September 4, 2018
• Sponsor: Phillip Brian Smith
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Phillip Brian Smith, Duke University

Tracking Information

• First Submitted Date: November 13, 2008
• First Posted Date: November 17, 2008
• Last Update Posted Date: September 4, 2018
• Study Start Date: December 2008
• Actual Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 13, 2008): Reduced bioavailability of oral voriconazole in pediatric patients status post stem cell transplantation with gastrointestinal graft versus host disease [ Time Frame: one year ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: November 13, 2008): Pharmacokinetics(including clearance, maximum concentration, area under the time concentration curve, and half life) of voriconazole in pediatric patients status post hematopoietic stem cell transplantation. [ Time Frame: one year ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Voriconazole Pharmacokinetics in Children With Gastrointestinal Graft Versus Host Disease
• Official Title: Define the Pharmacokinetics of Oral Voriconazole in Children With Extensive Gastrointestinal Graft Versus Host Disease

Brief Summary

Determine how much voriconazole is absorbed when the product is given by mouth to children with extensive graft versus host disease after a stem cell transplantation and determine the correct dosing of voriconazole in this population.

Hypothesis: Children with gastrointestinal graft versus host disease will have decreased absorption of oral voriconazole and require higher doses of voriconazole in order to prevent or treat fungal infections.

• Detailed Description: Disseminated fungal infections are a leading cause of mortality in children who receive hematopoietic stem cell transplantation (SCT). Therefore, children routinely receive prophylactic and empirical antifungal therapy after SCT. The most commonly used antifungal agent in this population is voriconazole. Voriconazole can be given via intravenous or oral routes and children who are post SCT are routinely switched from the intravenous to oral formulation at the time of hospital discharge. However, the absorption and systemic exposure of oral voriconazole has not been well-described in children. Furthermore, many children who undergo transplantation develop gastrointestinal graft versus host disease and this likely impacts oral absorption. The magnitude of effect resulting from graft versus host disease on absorption of voriconazole and subsequent blood concentrations in children is unknown. Thus children with graft versus host disease are at a particularly high risk of inadequate absorption with subsequent sub-therapeutic levels of voriconazole. They may need higher or more frequent dosing to achieve therapeutic levels. The purpose of my research project is to define the pharmacokinetics of oral voriconazole and establish dosing guidelines in children following SCT.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Graft Versus Host Disease
• Stem Cell Transplantation

Intervention

Drug: voriconazole

Voriconazole formulation will be changed from oral to intravenous at the same dose the subject is currently receiving per standard of care.

Study Arms

• Experimental: graft versus host disease
  Patients receiving oral voriconazole will be switched to intravenous voriconazole. Pharmacokinetics will be determined after each formulation.
  Intervention: Drug: voriconazole
• Experimental: No graft versus host disease
  Patients receiving oral voriconazole will be switched to intravenous voriconazole. Pharmacokinetics will be determined after each formulation.
  Intervention: Drug: voriconazole

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 14, 2012): 5
• Original Estimated Enrollment (submitted: November 13, 2008): 36
• Actual Study Completion Date: July 2012
• Actual Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age ≤ 18 years, sufficient venous access to permit administration of voriconazole, ability to take oral medications, written informed consent provided by the parent or legally authorized representative, and Grade II or higher (extensive) gastrointestinal graft versus host disease for those patients in the graft versus host disease patient subset.

Exclusion Criteria:

• History of anaphylaxis attributed to voriconazole or other triazole compounds, any concomitant condition, which in the opinion of the investigator would preclude a patient's participation in the study, or previous participation in this study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00792246
• Other Study ID Numbers: Pro00004318
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Phillip Brian Smith, Duke University
• Study Sponsor: Phillip Brian Smith
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: P Brian Smith, MD; Duke Unviersity Medical Center

• PRS Account: Duke University
• Verification Date: August 2018