Clinical trial NCT03241550: A Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients
Official title: A Phase 1, Open-label, Multicenter, Non-comparative Pharmacokinetics and Safety Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hematological Malignancy
Keywords: invasive fungal disease
Cresemba®
Hematological malignancy
isavuconazonium sulfate
ASP9766
isavuconazole
pediatric population
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Basilea Pharmaceutica International Ltd
First posted: 2017-08-07
Enrollment: 49
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the pharmacokinetics (PK), safety and tolerability of multiple doses of intravenous (IV) and oral isavuconazonium sulfate administered daily in pediatric patients. The PK data will be utilized to establish a pediatric population PK model of isavuconazole, the active moiety of isavuconazonium sulfate.


Eligibility criteria: Inclusion Criteria:

* Subject has sufficient venous access to permit administration of study drug (for the IV cohorts), collection of pharmacokinetic samples and monitoring of safety laboratories.
* Female subject must either:

  * Be of non-childbearing potential: Clearly premenarchal or documented surgically sterile
  * Or, if of childbearing potential: Agree not to try to become pregnant during the study and for 28 days after the final study drug administration; and have a negative urine or serum pregnancy test at screening; and, if heterosexually active, agree to consistently use 2 forms of highly effective birth control (at least one of which must be a barrier method) starting at screening and throughout the study and for 28 days after the final study drug administration.
* Female subject who is of childbearing potential must agree not to breastfeed starting at screening and throughout the study and for 28 days after the final study drug administration.
* Female subject who is of childbearing potential must not donate ova starting at screening and throughout the study and for 28 days after the final study drug administration.
* Male subject who is of childbearing potential and their female spouse/partner who is of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (at least one of which must be a barrier method) starting at screening and continue throughout the study, and for 90 days after the final study drug administration.
* Male subject who is of childbearing potential must not donate sperm starting at screening and throughout the study and, for 90 days after the final study drug administration.
* Subject and subject's parent(s) or legal guardian agree that the subject will not participate in another interventional study while on treatment.
* For oral cohorts: subject is able to swallow the oral capsule medication.

Exclusion Criteria:

* Subject has familial short QT syndrome, is receiving medications that are known to shorten the QT interval, or has a clinically significant abnormal electrocardiogram (ECG).
* Subject has evidence of hepatic dysfunction defined as:

  * Total bilirubin ≥ 3 times the upper limit of normal (ULN)
  * Alanine transaminase or aspartate transaminase ≥ 5 times the ULN
  * Known cirrhosis or chronic hepatic failure
* Subject has used strong cytochrome P450 (CYP) 3A4 inhibitors or inducers such as ketoconazole, rifampin/rifampicin, long acting barbiturates, carbamazepine and St. John's wort in the 5 days prior to the first administration of study drug.
* Subject has known history of allergy, hypersensitivity, or any serious reaction to any of the azole class antifungals.
* Subject has any condition which makes the subject unsuitable for study participation.
* Subject is unlikely to survive 30 days.
* Subject has received investigational therapy, with the exception of oncology drug trials, within 28 days or 5 half-lives, whichever is longer, prior to screening.
* For oral cohorts: The subject has gastrointestinal disease or has had a procedure that is expected to interfere with the oral absorption or tolerance of the study drug (e.g., functionally relevant gastrointestinal obstruction, mucositis/stomatitis, or frequent vomiting).
* Subject previously dosed with isavuconazonium sulfate.

Primary outcomes:
measure: Pharmacokinetics (PK) of isavuconazole in plasma: Cmax at steady state
timeFrame: Up to 7 days
measure: PK of isavuconazole in plasma: AUCtau
timeFrame: Up to 7 days
measure: PK of isavuconazole in plasma: tmax
timeFrame: Up to 7 days
measure: PK of isavuconazole in plasma: Ctrough
timeFrame: Up to 28 days
measure: PK of isavuconazole in plasma: CL
timeFrame: Up to 28 days
measure: PK of isavuconazole in plasma: Vss
timeFrame: Up to 28 days
measure: PK of isavuconazole in plasma: AUCss
timeFrame: Up to 28 days
measure: PK of isavuconazole in plasma: t 1/2
timeFrame: Up to 28 days
measure: Safety assessed by nature, frequency and severity of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 58 days
measure: Number of patients with vital sign abnormalities and/or adverse events
timeFrame: Up to 28 days
measure: Number of patients with laboratory value abnormalities and/or adverse events
timeFrame: Up to 28 days
measure: Safety assessed by routine 12- lead electrocardiogram (ECG)
timeFrame: Up to 28 days
Secondary outcomes:
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Miller Children's Hospital
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Orange
country: United States
facility: CHOC Children's Hospital of Orange County
state: California
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H Lurie Children's Hospital of Chicago
state: Illinois
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Kansas City
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospital of Cleveland
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: The Children's Hospital at TriStar Centennial Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Senior Medical Director
role: STUDY_DIRECTOR
References:
citation: Arrieta AC, Neely M, Day JC, Rheingold SR, Sue PK, Muller WJ, Danziger-Isakov LA, Chu J, Yildirim I, McComsey GA, Frangoul HA, Chen TK, Statler VA, Steinbach WJ, Yin DE, Hamed K, Jones ME, Lademacher C, Desai A, Micklus K, Phillips DL, Kovanda LL, Walsh TJ. Safety, Tolerability, and Population Pharmacokinetics of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients. Antimicrob Agents Chemother. 2021 Jul 16;65(8):e0029021. doi: 10.1128/AAC.00290-21. Epub 2021 Jul 16.