A PhaseI/II, Open Label Multi-Centre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the JAK2 Inhibitor AZD1480 Administered Orally to Patients With Primary Myelofibrosis (PMF) and Post-Polycythaemia Vera/Essential Thrombocythaemia Myelofibrosis (Post-PV/ET MF
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Pharamcokinetic Parameters Following Single Dosing: Tmax
研究概览
简要总结
This study is being conducted to test study drug AZD1480 to see how it may work to treat myeloproliferative diseases. The main purpose of this study is to determine the safety and tolerability of AZD1480. This is the first time the drug has been given to humans and is classed as a first time in man study. Its main purpose is to establish a safe dosage of the drug and provide additional information on any potential side effects this drug may cause. The study will also assess the blood levels and action of AZD1480 in the body over a period of time and will indicate whether the drug has a therapeutic effect on myeloproliferative diseases.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 25 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with myelofibrosis requiring therapy
- •Evidence of post-menopausal status or sterile
- •ECOG Performance Status </=2
排除标准
- •Prior therapy with any JAK2 medications
- •Significant lung disorder or lung disease
- •Previous radiation therapy to chest wall or chest infection requiring antibiotic treatment within 28 days before study screening
- •Eye disease of the cornea
- •Patients requiring oxygen supplementation
- •Ejection fraction <45% (ECHO/MUGA) or significant pulmonary hypertension >40 mm Hg (by Echo/Doppler)
- •Forced Expiratory Volume (FEV1)/Forced Vital Capacity (FVC) <70% predicted or >130% predicted
- •Diffusing capacity of the Lung for Carbon Monoxide (DLCO) corrected for hemoglobin <60% predicted, oxygen saturation <88% at rest or after a 6-minute flat walk, without supplemental oxygen
- •Chest infection requiring antibiotics within 7 days of the first dose of Investigational product.
研究组 & 干预措施
1
AZD1480
干预措施: AZD1480 (Drug)
结局指标
主要结局
Pharamcokinetic Parameters Following Single Dosing: Tmax
时间窗: 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose)
Single dose Tmax (h)
Pharmacokinetic Parameters Following Single Dosing: AUC0-12
时间窗: 0 to 12 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post dose)
Single dose AUC0-12 (ug\*h/L)
Pharmacokinetic Parameters Following Single Dosing: Vz/F
时间窗: 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose)
Single dose Vz/F (L)
Pharmacokinetic Parameters Following Multiple Dosing: Cmax,ss
时间窗: On Days 1 and 28 at 0, 0,5, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose, and at 0, 2, 4 hours post dose on Days 4 and 10
Multiple dose Cmax,ss (ug/L)
Pharmacokinetic Parameters Following Single Dosing: Cmax
时间窗: 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose)
Single dose Cmax (ug/L)
Pharmacokinetic Parameters Following Multiple Dosing: Cmin,ss
时间窗: On Days 1 and 28 at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose and at 0, 2, 4 hours post-dose on Days 4 and 10.
Multiple dose Cmin,ss (ug/L)
Pharmacokinetic Parameters Following Single Dosing: CL/F
时间窗: 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose)
Single dose CL/F (L/h)
Pharmacokinetic Parameters Following Single Dosing: AUC0-24
时间窗: 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose)
Single dose AUC0-24 (ug\*h/L)
Pharmacokinetic Parameters Following Single Dosing:AUC0-inf
时间窗: 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose)
Single dose AUC(0 to infinity) (ug\*h/L)
Pharmacokinetic Parameters Following Multiple Dosing: CLss/F
时间窗: On Days 1 and 28 at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 hours post dose and at 0, 2, 4 hours post-dose
Multiple dose CLss/F (L/h)
Pharamcokinetic Parameters Following Multiple Dosing: Tmax,ss
时间窗: On Days 1 and 28 at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose and at 0, 2, 4 hours post-dose on Days 4 and 10
Multiple dose Tmax,ss (h)
Inhibition of PSTAT3 (Count)
时间窗: 2hrs and 4 hrs post dose
PSTAT3 inhinition
次要结局
未报告次要终点