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A Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03241550
Recruitment Status : Completed
First Posted : August 7, 2017
Last Update Posted : July 2, 2020
Sponsor:
Collaborator:
Basilea Pharmaceutica International Ltd
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

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

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Study Type : Interventional  (Clinical Trial)
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 : October 2, 2017
Actual Primary Completion Date : July 5, 2019
Actual Study Completion Date : July 5, 2019

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Cresemba®




Primary Outcome Measures :
  1. Pharmacokinetics (PK) of isavuconazole in plasma: Cmax at steady state [ Time Frame: Up to 7 days ]
    Maximum concentration at steady state (Cmax) will be derived from the PK plasma samples collected.

  2. PK of isavuconazole in plasma: AUCtau [ Time Frame: 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.

  3. PK of isavuconazole in plasma: tmax [ Time Frame: Up to 7 days ]
    Time of maximum concentration (tmax) will be derived from the PK plasma samples collected.

  4. PK of isavuconazole in plasma: Ctrough [ Time Frame: Up to 28 days ]
    Concentration - trough level (Ctrough) will be derived from the PK plasma samples collected.

  5. PK of isavuconazole in plasma: CL [ Time Frame: Up to 28 days ]
    Clearance (CL) will be model-derived.

  6. PK of isavuconazole in plasma: Vss [ Time Frame: Up to 28 days ]
    Volume of distribution at steady state (Vss) will be model-derived.

  7. PK of isavuconazole in plasma: AUCss [ Time Frame: Up to 28 days ]
    Area under the concentration-time curve at steady state (AUCss) will be model-derived.

  8. PK of isavuconazole in plasma: t 1/2 [ Time Frame: Up to 28 days ]
    Half-life (t1/2) will be model-derived.

  9. Safety assessed by nature, frequency and severity of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 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.

  10. Number of patients with vital sign abnormalities and/or adverse events [ Time Frame: 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.

  11. Number of patients with laboratory value abnormalities and/or adverse events [ Time Frame: 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.

  12. Safety assessed by routine 12- lead electrocardiogram (ECG) [ Time Frame: 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.



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Ages Eligible for Study:   1 Year to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03241550


Locations
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United States, California
Miller Children's Hospital
Long Beach, California, United States, 90806
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
CHOC Children's Hospital of Orange County
Orange, California, United States, 92868
United States, Florida
Nicklaus Children's Hospital
Miami, Florida, United States, 33155
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
United States, Illinois
Ann & Robert H Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Minnesota
Children's Hospitals and Clinics of Minnesota
Minneapolis, Minnesota, United States, 55404
United States, Missouri
Children's Mercy Kansas City
Kansas City, Missouri, United States, 64108
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
University Hospital of Cleveland
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
The Children's Hospital at TriStar Centennial Medical Center
Nashville, Tennessee, United States, 37203
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75235
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Basilea Pharmaceutica International Ltd
Investigators
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Study Director: Senior Medical Director Astellas Pharma Global Development, Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT03241550    
Other Study ID Numbers: 9766-CL-0046
First Posted: August 7, 2017    Key Record Dates
Last Update Posted: July 2, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
invasive fungal disease
Cresemba®
Hematological malignancy
isavuconazonium sulfate
ASP9766
isavuconazole
pediatric population
Additional relevant MeSH terms:
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Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Isavuconazole
Antifungal Agents
Anti-Infective Agents