Phase 1B Study of the Safety, Tolerance, and Pharmacokinetics of Oral Posaconazole in Immunocompromised Children With Neutropenia (P03579)
Overview
- Phase
- Phase 1
- Intervention
- Posaconazole 12 mg/kg/day BID
- Conditions
- Fungal Infections
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 142
- Primary Endpoint
- Average Concentration of Posaconazole (Cavg) on Day 1 (Single Dose)
- Status
- Terminated
- Last Updated
- 7 years ago
Overview
Brief Summary
The purpose of this dose-escalation study is to evaluate the pharmacokinetics, safety, and tolerability of oral posaconazole in immunocompromised children with neutropenia or expected neutropenia.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Documented or anticipated neutropenia expected to last at least 7 days and only in the following clinical situations: acute leukemia; myelodysplasia; severe aplastic anemia; autologous hematopoietic stem cell transplantation (HSCT) recipients; high risk neuroblastoma; advanced stage non-Hodgkin's lymphoma; recipients of allogeneic HSCT during the pre-engraftment (neutropenia) period
- •Participants of child-bearing potential must use a medically accepted method of
- •contraception throughout the study and for at least 30 days after stopping study medication, unless they are surgically or medically sterile or agree to remain abstinent.
Exclusion Criteria
- •Proven invasive fungal infection (IFI) before study entry
- •Severe nausea and/or vomiting at screening
- •Received posaconazole within 10 days before screening
- •Unable to receive study drug by mouth or via an intestinal (enteral) tube
- •Females who are pregnant, intend to become pregnant during the study, or are breastfeeding
- •History of anaphylaxis attributed to the azole class of antifungal agents
Arms & Interventions
POS 12 BID 2 to <7 Years
Participants aged 2 to \<7 years received posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Intervention: Posaconazole 12 mg/kg/day BID
POS 12 BID 7 to <18 Years
Participants aged 7 to \<18 years received posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Intervention: Posaconazole 12 mg/kg/day BID
POS 18 BID 2 to <7 Years
Participants aged 2 to \<7 years received posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Intervention: Posaconazole 18 mg/kg/day BID
POS 18 BID 7 to <18 Years
Participants aged 7 to \<18 years received posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.
Intervention: Posaconazole 18 mg/kg/day BID
POS 18 TID 2 to <7 Years
Participants aged 2 to \<7 years received posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.
Intervention: Posaconazole 18 mg/kg/day TID
POS 18 TID 7 to <18 Years
Participants aged 7 to \<18 years received posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.
Intervention: Posaconazole 18 mg/kg/day TID
POS 12 TID 3 months to <2 Years
Participants aged 3 months to \<2 years received posaconazole oral suspension 12 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.
Intervention: Posaconazole 12 mg/kg/day TID
Outcomes
Primary Outcomes
Average Concentration of Posaconazole (Cavg) on Day 1 (Single Dose)
Time Frame: Up to 12 hours after the first dose (BID dose groups) or up to 8 hours after the first dose (TID dose (TID dose groups)
Blood samples for determination of plasma posaconazole concentration were collected predose and approximately 3, 5, 8, and 12 hours after the first dose on Day 1. The 12-hour sample was not obtained for the TID dose groups. Day 1 pharmacokinetic samples were not collected for participants 3 months to \<2 years of age weighing \<6.5 kg.
Average Concentration of Posaconazole (Cavg) on Day 7 (Steady State)
Time Frame: Up to 12 hours after the first dose on Day 7 (BID dose groups) or up to 8 hours after the first dose on Day 7 (TID dose
Blood samples for determination of plasma posaconazole concentration were collected predose and approximately 3, 5, 8, and 12 hours after the first dose on Day 7 (steady state). The 12-hour sample was not obtained for the TID dose groups. The target Cavg range was 500 to \<2500 ng/mL.
Secondary Outcomes
- Number of Participants With an Adverse Event(Up to Day 58)
- Number of Participants With an Adverse Event Leading to Study Drug Discontinuation(Up to Day 28)