A Phase 1, Open-label, Multicenter, Non-comparative Pharmacokinetics and Safety Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 16
- 主要终点
- PK of isavuconazole in plasma: t 1/2
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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).
干预措施: isavuconazonium sulfate - intravenous (Drug)
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).
干预措施: isavuconazonium sulfate - intravenous (Drug)
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).
干预措施: isavuconazonium sulfate - intravenous (Drug)
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).
干预措施: isavuconazonium sulfate - oral (Drug)
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).
干预措施: isavuconazonium sulfate - oral (Drug)
结局指标
主要结局
PK of isavuconazole in plasma: t 1/2
时间窗: Up to 28 days
Half-life (t1/2) will be model-derived.
Pharmacokinetics (PK) of isavuconazole in plasma: Cmax at steady state
时间窗: Up to 7 days
Maximum concentration at steady state (Cmax) will be derived from the PK plasma samples collected.
PK of isavuconazole in plasma: tmax
时间窗: Up to 7 days
Time of maximum concentration (tmax) will be derived from the PK plasma samples collected.
PK of isavuconazole in plasma: Vss
时间窗: Up to 28 days
Volume of distribution at steady state (Vss) will be model-derived.
PK of isavuconazole in plasma: Ctrough
时间窗: Up to 28 days
Concentration - trough level (Ctrough) will be derived from the PK plasma samples collected.
PK of isavuconazole in plasma: AUCtau
时间窗: 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: CL
时间窗: Up to 28 days
Clearance (CL) will be model-derived.
Safety assessed by nature, frequency and severity of Treatment Emergent Adverse Events (TEAEs)
时间窗: 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.
PK of isavuconazole in plasma: AUCss
时间窗: Up to 28 days
Area under the concentration-time curve at steady state (AUCss) will be model-derived.
Number of patients with vital sign abnormalities and/or adverse events
时间窗: 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
时间窗: 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)
时间窗: 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.
次要结局
未报告次要终点