A Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients

Astellas

Status and phase: Completed; Phase 1

Conditions: Hematological Malignancy

Treatments: Drug: isavuconazonium sulfate - intravenous; Drug: isavuconazonium sulfate - oral

Study type: Interventional

Funder types: Industry

Identifiers

NCT03241550

9766-CL-0046

Details and patient eligibility

About

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.

Enrollment: 49 patients

Sex: All

Ages: 1 to 17 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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49 participants in 5 patient groups

isavuconazonium sulfate IV cohort 1: 1 to < 6 years of age

Experimental group

Description:

Patients 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).

Treatment:

Drug: isavuconazonium sulfate - intravenous

isavuconazonium sulfate IV cohort 2: 6 to < 12 years of age

Experimental group

Description:

Patients 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).

Treatment:

Drug: isavuconazonium sulfate - intravenous

isavuconazonium sulfate IV cohort 3: 12 to < 18 years of age

Experimental group

Description:

Patients 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).

Treatment:

Drug: isavuconazonium sulfate - intravenous

isavuconazonium sulfate oral cohort 4: 6 to < 12 years of age

Experimental group

Description:

Patients 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).

Treatment:

Drug: isavuconazonium sulfate - oral

isavuconazonium sulfate oral cohort 5: 12 to < 18 years of age

Experimental group

Description:

Patients 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).

Treatment:

Drug: isavuconazonium sulfate - oral