A Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients
A Phase 1, Open-label, Multicenter, Non-comparative Pharmacokinetics and Safety Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients
1 other identifier
interventional
49
1 country
16
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Oct 2017
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 3, 2017
CompletedFirst Posted
Study publicly available on registry
August 7, 2017
CompletedStudy Start
First participant enrolled
October 2, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 5, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
July 5, 2019
CompletedNovember 19, 2024
November 1, 2024
1.8 years
August 3, 2017
November 15, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (12)
Pharmacokinetics (PK) of isavuconazole in plasma: Cmax at steady state
Maximum concentration at steady state (Cmax) will be derived from the PK plasma samples collected.
Up to 7 days
PK of isavuconazole in plasma: AUCtau
Area under the concentration time curve from the time of dosing to the start of next dosing interval at multiple dose conditions (AUCtau) will be derived from the PK plasma samples collected.
Up to 7 days
PK of isavuconazole in plasma: tmax
Time of maximum concentration (tmax) will be derived from the PK plasma samples collected.
Up to 7 days
PK of isavuconazole in plasma: Ctrough
Concentration - trough level (Ctrough) will be derived from the PK plasma samples collected.
Up to 28 days
PK of isavuconazole in plasma: CL
Clearance (CL) will be model-derived.
Up to 28 days
PK of isavuconazole in plasma: Vss
Volume of distribution at steady state (Vss) will be model-derived.
Up to 28 days
PK of isavuconazole in plasma: AUCss
Area under the concentration-time curve at steady state (AUCss) will be model-derived.
Up to 28 days
PK of isavuconazole in plasma: t 1/2
Half-life (t1/2) will be model-derived.
Up to 28 days
Safety assessed by nature, frequency and severity of Treatment Emergent Adverse Events (TEAEs)
A TEAE is defined as an Adverse Event (AE) observed after starting administration of the study drug through follow-up. AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). Number of patients with TEAE's will be summarized.
Up to 58 days
Number of patients with vital sign abnormalities and/or adverse events
An abnormality identified during a medical test (e.g. vital signs) should be defined as an AE only if the abnormality meets 1 of the following criteria: induces clinical signs or symptoms; requires active intervention; requires interruption or discontinuation of study drug; or the abnormality or test value is clinically significant.
Up to 28 days
Number of patients with laboratory value abnormalities and/or adverse events
An abnormality identified during a medical test (e.g. laboratory parameter) should be defined as an AE only if the abnormality meets 1 of the following criteria: induces clinical signs or symptoms; requires active intervention; requires interruption or discontinuation of study drug; or the abnormality or test value is clinically significant.
Up to 28 days
Safety assessed by routine 12- lead electrocardiogram (ECG)
Standard 12-lead ECG recordings will be used for the purposes of safety assessment. A 12-lead, resting ECG is to be recorded. Patients should remain supine for at least 5 minutes prior to all ECGs being performed. The results (normal, abnormal not clinically significant, abnormal clinically significant) are to be recorded.
Up to 28 days
Study Arms (5)
isavuconazonium sulfate IV cohort 1: 1 to < 6 years of age
EXPERIMENTALPatients will receive an intravenous (IV) loading regimen of isavuconazonium sulfate, which consists of a dose every 8 hours (+/- 2 hours) on days 1 and 2, followed by once daily IV maintenance dosing for up to 26 additional days (for a maximum of 28 days of dosing).
isavuconazonium sulfate IV cohort 2: 6 to < 12 years of age
EXPERIMENTALPatients will receive an IV loading regimen of isavuconazonium sulfate, which consists of a dose every 8 hours (+/- 2 hours) on days 1 and 2, followed by once daily IV maintenance dosing for up to 26 additional days (for a maximum of 28 days of dosing).
isavuconazonium sulfate IV cohort 3: 12 to < 18 years of age
EXPERIMENTALPatients will receive an IV loading regimen of isavuconazonium sulfate, which consists of a dose every 8 hours (+/- 2 hours) on days 1 and 2, followed by once daily IV maintenance dosing for up to 26 additional days (for a maximum of 28 days of dosing).
isavuconazonium sulfate oral cohort 4: 6 to < 12 years of age
EXPERIMENTALPatients will receive a loading regimen of isavuconazonium sulfate by oral administration, comprising one dose every 8 hours (+/- 2 hours) on days 1 and 2 (a total of six doses), followed by once daily oral maintenance dosing for up to 26 additional days (for a maximum of 28 days of dosing).
isavuconazonium sulfate oral cohort 5: 12 to < 18 years of age
EXPERIMENTALPatients will receive a loading regimen of isavuconazonium sulfate by oral administration, comprising one dose every 8 hours (+/- 2 hours) on days 1 and 2 (a total of six doses), followed by once daily oral maintenance dosing for up to 26 additional days (for a maximum of 28 days of dosing).
Interventions
IV infusion
Oral
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (16)
Miller Children's Hospital
Long Beach, California, 90806, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
CHOC Children's Hospital of Orange County
Orange, California, 92868, United States
Nicklaus Children's Hospital
Miami, Florida, 33155, United States
Emory University School of Medicine
Atlanta, Georgia, 30322, United States
Ann & Robert H Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611, United States
University of Louisville
Louisville, Kentucky, 40202, United States
Children's Hospitals and Clinics of Minnesota
Minneapolis, Minnesota, 55404, United States
Children's Mercy Kansas City
Kansas City, Missouri, 64108, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
University Hospital of Cleveland
Cleveland, Ohio, 44106, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
The Children's Hospital at TriStar Centennial Medical Center
Nashville, Tennessee, 37203, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75235, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
Related Publications (1)
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.
PMID: 34031051DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Senior Medical Director
Astellas Pharma Global Development, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 3, 2017
First Posted
August 7, 2017
Study Start
October 2, 2017
Primary Completion
July 5, 2019
Study Completion
July 5, 2019
Last Updated
November 19, 2024
Record last verified: 2024-11
Data Sharing
- IPD Sharing
- Will not share
Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.