A Study of the Safety, Tolerance, and Pharmacokinetics of Oral Posaconazole in Immunocompromised Children (P03579)

Study Overview
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Brief Summary
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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.

Official Title
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Phase 1B Study of the Safety, Tolerance, and Pharmacokinetics of Oral Posaconazole in Immunocompromised Children With Neutropenia (P03579)

Conditions
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Fungal Infections

Intervention / Treatment
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* Drug: Posaconazole 12 mg/kg/day BID
* Drug: Posaconazole 18 mg/kg/day BID
* Drug: Posaconazole 18 mg/kg/day TID
* Drug: Posaconazole 12 mg/kg/day TID


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: POS 12 BID 2 to <7 Years<br>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. | Drug: Posaconazole 12 mg/kg/day BID<br>* Posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) (maximum 800 mg/day)<br>* Other names: Noxafil®;|
| Experimental: POS 12 BID 7 to <18 Years<br>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. | Drug: Posaconazole 12 mg/kg/day BID<br>* Posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) (maximum 800 mg/day)<br>* Other names: Noxafil®;|
| Experimental: POS 18 BID 2 to <7 Years<br>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. | Drug: Posaconazole 18 mg/kg/day BID<br>* Posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) (maximum 1200 mg/day)<br>* Other names: Noxafil®;|
| Experimental: POS 18 BID 7 to <18 Years<br>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. | Drug: Posaconazole 18 mg/kg/day BID<br>* Posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) (maximum 1200 mg/day)<br>* Other names: Noxafil®;|
| Experimental: POS 18 TID 2 to <7 Years<br>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. | Drug: Posaconazole 18 mg/kg/day TID<br>* Posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) (maximum 1200 mg/day)<br>* Other names: Noxafil®;|
| Experimental: POS 18 TID 7 to <18 Years<br>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. | Drug: Posaconazole 18 mg/kg/day TID<br>* Posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) (maximum 1200 mg/day)<br>* Other names: Noxafil®;|
| Experimental: POS 12 TID 3 months to <2 Years<br>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. | Drug: Posaconazole 12 mg/kg/day TID<br>* Posaconazole oral suspension 12 mg/kg/day divided into 3 doses (TID) (maximum 800 mg/day)<br>* Other names: Noxafil®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Concentration of Posaconazole (Cavg) on Day 1 (Single 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 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. | 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) | 
| Average Concentration of Posaconazole (Cavg) on Day 7 (Steady State) | 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. | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With an Adverse Event | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions. | Up to Day 58 | 
| Number of Participants With an Adverse Event Leading to Study Drug Discontinuation | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions. | Up to Day 28 |