Safety and Pharmacokinetics of Intravenous and Oral Posaconazole in Immunocompromised Children (MK-5592-097)

NCT ID: NCT02452034

Last Updated: 2019-07-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-07
• Study Completion Date: 2018-09-03

Brief Summary

This study aims to evaluate the pharmacokinetics of posaconazole (POS) administered intravenously (IV) or orally to immunocompromised pediatric participants.

Conditions

Neutropenia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

3.5 mg/kg POS (2<7 years old)

Children 2 to less than 7 years of age will receive POS at 3.5 mg/kg by intravenous (IV) solution twice on Day 1, then once daily on Days 2-10. This will be followed by treatment with 3.5 mg/kg POS once daily by powder for oral suspension (PFS) for a minimum of 10 days; or, if they are unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

Group Type: EXPERIMENTAL

Posaconazole IV solution

Intervention Type: DRUG

Posaconazole by IV solution twice on Day 1, then once daily on Days 2-10.

Posaconazole powder for oral suspension

Intervention Type: DRUG

Posaconazole once daily by PFS for a minimum of 10 days

4.5 mg/kg POS (2<7 years old)

Children 2 to less than 7 years of age will receive POS at 4.5 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This will be followed by treatment with 4.5 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they are unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

Group Type: EXPERIMENTAL

Posaconazole IV solution

Intervention Type: DRUG

Posaconazole by IV solution twice on Day 1, then once daily on Days 2-10.

Posaconazole powder for oral suspension

Intervention Type: DRUG

Posaconazole once daily by PFS for a minimum of 10 days

3.5 mg/kg POS (7-17 years old)

Children 7 to 17 years of age will receive POS at 3.5 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This will be followed by treatment with 3.5 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they are unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

Group Type: EXPERIMENTAL

Posaconazole IV solution

Intervention Type: DRUG

Posaconazole by IV solution twice on Day 1, then once daily on Days 2-10.

Posaconazole powder for oral suspension

Intervention Type: DRUG

Posaconazole once daily by PFS for a minimum of 10 days

4.5 mg/kg POS (7-17 years old)

Children 7 to 17 years of age will receive POS at 4.5 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This will be followed by treatment with 4.5 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they are unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

Group Type: EXPERIMENTAL

Posaconazole IV solution

Intervention Type: DRUG

Posaconazole by IV solution twice on Day 1, then once daily on Days 2-10.

Posaconazole powder for oral suspension

Intervention Type: DRUG

Posaconazole once daily by PFS for a minimum of 10 days

6 mg/kg POS (2<7 years old)

Children 2 to less than 7 years of age will receive POS at 6 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This will be followed by treatment with 6 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they are unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

Group Type: EXPERIMENTAL

Posaconazole IV solution

Intervention Type: DRUG

Posaconazole by IV solution twice on Day 1, then once daily on Days 2-10.

Posaconazole powder for oral suspension

Intervention Type: DRUG

Posaconazole once daily by PFS for a minimum of 10 days

6 mg/kg POS (7-17 years old)

Children 7 to 17 years of age will receive POS at 6 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This will be followed by treatment with 6 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they are unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

Group Type: EXPERIMENTAL

Posaconazole IV solution

Intervention Type: DRUG

Posaconazole by IV solution twice on Day 1, then once daily on Days 2-10.

Posaconazole powder for oral suspension

Intervention Type: DRUG

Posaconazole once daily by PFS for a minimum of 10 days

Interventions

Posaconazole IV solution

Posaconazole by IV solution twice on Day 1, then once daily on Days 2-10.

Intervention Type: DRUG

Posaconazole powder for oral suspension

Posaconazole once daily by PFS for a minimum of 10 days

Intervention Type: DRUG

Other Intervention Names

Noxafil; Noxafil

Eligibility Criteria

Inclusion Criteria

• Have documented or anticipated neutropenia expected to last for at least 7 days, following treatment in at least one of the following clinical situations: acute leukemia, myelodysplasia, severe aplastic anemia, recipients of Autologous Hematopoietic Stem Cell Transplant (HSCT), high risk neuroblastoma, advanced stage non-Hodgkin's lymphoma, hemophagocytic lymphohistiocytosis
• Have a central line in place prior to IV study therapy
• Participants of reproductive potential agree to remain abstinent, or use a medically accepted method of birth control

Exclusion Criteria

• Has a proven or probable invasive fungal infection
• Has received any formulation of POS within prior 10 days
• Is receiving any prohibited drugs
• Has laboratory results that are outside of normal limits at screening, as follows: a) Moderate or severe liver dysfunction, as defined as: Aspartate Aminotransferase (AST) > 5 times the upper limit of normal (ULN), OR Alanine Aminotransferase (ALT) > 5 times the ULN, OR Serum total bilirubin >2.5 times the ULN, OR AST or ALT > 3 times ULN with total bilirubin > 2 times ULN; b) Calculated creatinine clearance <30 mL/min.
• Has QTc (QT interval corrected for rate) prolongation defined as: a) Symptomatic QTc prolongation >450 msec (males) or >470 msec (females) OR b) Any QTc prolongation of >500 msec
• Is pregnant, intends to become pregnant during study, or is breastfeeding
• Has a history of anaphylaxis attributed to the azole class of antifungal agents
• Is not expected to receive a minimum of 10 days of POS IV solution
• Has participated in any Phase 1 Investigational New Drug (IND) study within prior 30 days or expects to do so within the following 60 days
• Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Groll AH, Abdel-Azim H, Lehrnbecher T, Steinbach WJ, Paschke A, Mangin E, Winchell GA, Waskin H, Bruno CJ. Pharmacokinetics and safety of posaconazole intravenous solution and powder for oral suspension in children with neutropenia: an open-label, sequential dose-escalation trial. Int J Antimicrob Agents. 2020 Sep;56(3):106084. doi: 10.1016/j.ijantimicag.2020.106084. Epub 2020 Jul 17.

Reference Type: DERIVED

PMID: 32682946 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2014-002807-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-5592-097

Identifier Type: OTHER

Identifier Source: secondary_id

5592-097

Identifier Type: -

Identifier Source: org_study_id