E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This is a phase I pharmacokinetic study and does not investigate a medical condition |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the pharmacokinetics (PK), safety and tolerability of multiple doses of 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.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Institutional Review Board (IRB) approved informed consent (IC).
2.Male or female subject 1 year to < 18 years of age for the IV cohorts or 6 years to <18 years of age for the oral cohorts.
3.Subject has sufficient venous access to permit administration of study drug (for the IV cohorts).
4.Female subject must either:
a.Be of non-childbearing potential
b.Or, if of childbearing potential:
●Agree not to try to become pregnant.
●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.
5.Female subject who is of childbearing potential must agree not to breastfeed.
6.Female subject who is of childbearing potential must not donate ova.
7.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.
8.Male subject who is of childbearing potential must not donate sperm.
9.Subject and subject’s parent(s) or legal guardian agree that the subject will not participate in another interventional study while on treatment.
10.For oral cohorts: subject is able to swallow the oral capsule study medication.
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E.4 | Principal exclusion criteria |
1.Subject has familial short QT syndrome, is receiving medications that are known to shorten the QT interval, or has a clinically significant abnormal ECG.
2.Subject has evidence of hepatic dysfunction, known cirrhosis or chronic hepatic failure.
3.Subject has used strong CYP3A4 inhibitors or inducers such as ketoconazole, rifampin/rifampicin, long acting barbiturates, carbamazepine and St. John’s wort.
4.Subject has known history of allergy, hypersensitivity, or any serious reaction to any of the azole class antifungals.
5.Subject is unlikely to survive 30 days in the investigator’s opinion.
6.Subject has received investigational therapy, with the exception of oncology drug trials. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetics Endpoints (IV and Oral)
●Cmax, AUCtau, tmax
●Ctrough
●Model-derived parameters: CL, Vss, AUCss, t1/2
Safety Variables (IV and Oral)
●Nature, frequency, and severity of treatment-emergent adverse events (TEAEs)
●Vital sign measurements (temperature, pulse rate and blood pressure)
●Laboratory assessments (hematology and chemistry)
●Routine 12-lead ECGs
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Cmax, AUCtau, tmax: Day 3 (IV only) and 7
Ctrough: Days 2, 3, 5, and 7
Model-derived parameters: CL, Vss, AUCss, t1/2: after completion of study
Nature, frequency, and severity of treatment-emergent adverse events (TEAEs): throughout the entire study period from screening to follow-up
Vital sign measurements (temperature, pulse rate and blood pressure): daily from Day 1 to Day 28 or End of Treatment (EOT)
Laboratory assessments (hematology and chemistry): Days 3, 7, 14, 21 and 28 or EOT
Routine 12-lead ECGs: Days 1, 7, 14 and 28 or EOT |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
pharmacokinetics and safety study |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |