A Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients

Hematological Malignancy Clinical Trial

Official title:

A Phase 1, Open-label, Multicenter, Non-comparative Pharmacokinetics and Safety Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03241550
• Other study ID #: 9766-CL-0046
• Status: Completed
• Phase: Phase 1
• Start date: October 2, 2017
• Est. completion date: July 5, 2019

Study information

• Verified date: March 2024
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: July 5, 2019
• Est. primary completion date: July 5, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematological Malignancy
• Neoplasms

Intervention

Drug:
• isavuconazonium sulfate - intravenous
IV infusion
• isavuconazonium sulfate - oral
Oral

Locations

Country	Name	City	State
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Ann & Robert H Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University Hospital of Cleveland	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Texas Children's Hospital	Houston	Texas
United States	Children's Mercy Kansas City	Kansas City	Missouri
United States	Miller Children's Hospital	Long Beach	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Nicklaus Children's Hospital	Miami	Florida
United States	Children's Hospitals and Clinics of Minnesota	Minneapolis	Minnesota
United States	The Children's Hospital at TriStar Centennial Medical Center	Nashville	Tennessee
United States	CHOC Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.	Basilea Pharmaceutica International Ltd

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	PK of isavuconazole in plasma: tmax	Time of maximum concentration (tmax) will be derived from the PK plasma samples collected.	Up to 7 days
Primary	PK of isavuconazole in plasma: Ctrough	Concentration - trough level (Ctrough) will be derived from the PK plasma samples collected.	Up to 28 days
Primary	PK of isavuconazole in plasma: CL	Clearance (CL) will be model-derived.	Up to 28 days
Primary	PK of isavuconazole in plasma: Vss	Volume of distribution at steady state (Vss) will be model-derived.	Up to 28 days
Primary	PK of isavuconazole in plasma: AUCss	Area under the concentration-time curve at steady state (AUCss) will be model-derived.	Up to 28 days
Primary	PK of isavuconazole in plasma: t 1/2	Half-life (t1/2) will be model-derived.	Up to 28 days
Primary	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
Primary	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
Primary	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
Primary	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

External Links

•   Link to plain language summary of the study on the Trial Results Summaries website
•   Link to results and other applicable study documents on the Astellas Clinical Trials website