A Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients

Sponsor

Astellas Pharma Global Development, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03241550

Collaborator

Basilea Pharmaceutica International Ltd (Industry)

Enrollment

Locations

Arms

21.1

Actual Duration (Months)

3.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hematological Malignancy	Drug: isavuconazonium sulfate - intravenous Drug: isavuconazonium sulfate - oral	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

49 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 2, 2017

Actual Primary Completion Date :

Jul 5, 2019

Actual Study Completion Date :

Jul 5, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: isavuconazonium sulfate IV cohort 1: 1 to < 6 years of age 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).	Drug: isavuconazonium sulfate - intravenous IV infusion Other Names: Cresemba®
Experimental: isavuconazonium sulfate IV cohort 2: 6 to < 12 years of age 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).	Drug: isavuconazonium sulfate - intravenous IV infusion Other Names: Cresemba®
Experimental: isavuconazonium sulfate IV cohort 3: 12 to < 18 years of age 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).	Drug: isavuconazonium sulfate - intravenous IV infusion Other Names: Cresemba®
Experimental: isavuconazonium sulfate oral cohort 4: 6 to < 12 years of age 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).	Drug: isavuconazonium sulfate - oral Oral Other Names: Cresemba®
Experimental: isavuconazonium sulfate oral cohort 5: 12 to < 18 years of age 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).	Drug: isavuconazonium sulfate - oral Oral Other Names: Cresemba®

Outcome Measures

Primary Outcome Measures

Pharmacokinetics (PK) of isavuconazole in plasma: Cmax at steady state [Up to 7 days]
Maximum concentration at steady state (Cmax) will be derived from the PK plasma samples collected.
PK of isavuconazole in plasma: AUCtau [Up to 7 days]
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.
PK of isavuconazole in plasma: tmax [Up to 7 days]
Time of maximum concentration (tmax) will be derived from the PK plasma samples collected.
PK of isavuconazole in plasma: Ctrough [Up to 28 days]
Concentration - trough level (Ctrough) will be derived from the PK plasma samples collected.
PK of isavuconazole in plasma: CL [Up to 28 days]
Clearance (CL) will be model-derived.
PK of isavuconazole in plasma: Vss [Up to 28 days]
Volume of distribution at steady state (Vss) will be model-derived.
PK of isavuconazole in plasma: AUCss [Up to 28 days]
Area under the concentration-time curve at steady state (AUCss) will be model-derived.
PK of isavuconazole in plasma: t 1/2 [Up to 28 days]
Half-life (t1/2) will be model-derived.
Safety assessed by nature, frequency and severity of Treatment Emergent Adverse Events (TEAEs) [Up to 58 days]
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.
Number of patients with vital sign abnormalities and/or adverse events [Up to 28 days]
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.
Number of patients with laboratory value abnormalities and/or adverse events [Up to 28 days]
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.
Safety assessed by routine 12- lead electrocardiogram (ECG) [Up to 28 days]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 17 Years

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Miller Children's Hospital	Long Beach	California	United States	90806
2	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
3	CHOC Children's Hospital of Orange County	Orange	California	United States	92868
4	Nicklaus Children's Hospital	Miami	Florida	United States	33155
5	Emory University School of Medicine	Atlanta	Georgia	United States	30322
6	Ann & Robert H Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
7	University of Louisville	Louisville	Kentucky	United States	40202
8	Children's Hospitals and Clinics of Minnesota	Minneapolis	Minnesota	United States	55404
9	Children's Mercy Kansas City	Kansas City	Missouri	United States	64108
10	Duke University Medical Center	Durham	North Carolina	United States	27710
11	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
12	University Hospital of Cleveland	Cleveland	Ohio	United States	44106
13	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
14	The Children's Hospital at TriStar Centennial Medical Center	Nashville	Tennessee	United States	37203
15	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75235
16	Texas Children's Hospital	Houston	Texas	United States	77030