A Phase 4, Open-Label, Single-Center Study to Assess Pharmacokinetic Characteristics and Safety of Endari in Patients With Sickle Cell Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Area Under Curve (AUC) of L-glutamine at 0.1 g/kg twice daily, 0.3 g/kg twice daily, and 0.6 g/kg once daily in SCD patients
研究概览
简要总结
L-glutamine has been approved in the US to reduce the acute complications of sickle cell disease (SCD) in adult and pediatric patients 5 years of age and older. The purpose of this single-center, open-label, phase 4 study is to evaluate the pharmacokinetic characteristics and safety of L-glutamine in patients with SCD.
详细描述
Sickle cell disease (SCD) is associated with a mutation in the β-hemoglobin gene that results in abnormal polymerization of hemoglobin. Polymerization of hemoglobin causes the red blood cell to sickle, leading to a cascade of events which cause acute complications for SCD patients.
L-glutamine has been approved in the US to reduce the acute complications of sickle cell disease (SCD) in adult and pediatric patients 5 years of age and older.
The purpose of this single-center, open-label, phase 4 study is to evaluate the pharmacokinetic characteristics and safety of L-glutamine in patients with SCD.
8 SCD patients and 4 healthy volunteers will receive weight-based dosing of L-glutamine for 3 weeks. Doses will be changed weekly: 0.1 g/kg administered twice daily during week 1, 0.3 g/kg administered twice daily during week 2, and 0.6 g/kg administered once daily during week 3.
The primary objective is to evaluate the pharmacokinetic characteristics of L-glutamine in SCD patients compared with healthy volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •5 years of age and older at Screening.
- •Has documented diagnosis of SCD with known genotype (HbSS, HbSβ0 and HbSC).
- •Written informed consent provided by patient or the patient's legally authorized representative.
- •Non-pregnant females of childbearing age must agree to avoid pregnancy during the study and to practice a recognized form of birth control during the course of the study (e.g., barrier, birth control pills, or abstinence).
- •Inclusion Criteria for Healthy Volunteers:
- •No known hematologic illness.
- •No known renal impairment.
- •18 Years of age or older at screening.
- •Written informed consent provided by patient or the patient's legally authorized representative.
- •African American and Hispanic participants preferred.
排除标准
- •Recent significant medical condition that required hospitalization (other than sickle cell crisis) within 2 months prior to starting L-glutamine therapy.
- •History of chronic kidney disease Stage 4 (glomerular filtration rate [GFR]=15-29) or Stage 5 (GFR<15 mL/min/1.73 m2).
- •History of chronic liver disease Child Pugh class C (10-15 points).
- •Received any blood products 3 months prior to starting L-glutamine therapy.
- •Currently pregnant or lactating or planning to conceive during the study period.
- •Currently taking or has taken any form of glutamine supplement within 30 days prior to starting L-glutamine therapy.
- •Has been treated with an investigational medication/treatment within 30 days prior to starting L-glutamine therapy.
- •Is currently enrolled in an investigational drug or device study and/or has participated in such a study within 30 days prior to starting L-glutamine therapy.
- •Factors that would, in the judgment of the investigator, make it difficult for the patient to comply with study requirements.
- •Patient is currently being treated with crizanlizumab or voxelotor.
- •Exclusion Criteria for Healthy Volunteers:
- •Known allergies to L-glutamine.
- •Informed consent document was not completed and signed.
- •Currently pregnant or lactating or planning to conceive during the study period.
- •Known hematologic illness, renal or hepatic impairment.
- •Received any blood products within 3 months of starting L-glutamine therapy.
研究组 & 干预措施
L-glutamine
Pharmacokinetic characteristics of L-glutamine
干预措施: L-glutamine (Drug)
结局指标
主要结局
Area Under Curve (AUC) of L-glutamine at 0.1 g/kg twice daily, 0.3 g/kg twice daily, and 0.6 g/kg once daily in SCD patients
时间窗: Week 1 Day 1 (0.1 g/kg dose) and Week 2 Day 1 (0.3 g/kg dose. Week 3 Day 1 and Week4 Day1 (0.6 g/kg once daily dose)
PK (AUC)
Maximum Plasma Concentration (Cmax) of L-glutamine at 0.1 g/kg twice daily, 0.3 g/kg twice daily, and 0.6 g/kg once daily in SCD patients
时间窗: Week 1 Day 1 (0.1 g/kg dose) and Week 2 Day 1 (0.3 g/kg dose. Week 3 Day 1 and Week4 Day1 (0.6 g/kg once daily dose)
PK (Cmax)
Half-life (t1/2) of L-glutamine at 0.1 g/kg twice daily, 0.3 g/kg twice daily, and 0.6 g/kg once daily in SCD patients
时间窗: Week 1 Day 1 (0.1 g/kg dose) and Week 2 Day 1 (0.3 g/kg dose. Week 3 Day 1 and Week4 Day1 (0.6 g/kg once daily dose)
PK (t1/2)
Time to Peak Concentration (Tmax) of L-glutamine at 0.1 g/kg twice daily, 0.3 g/kg twice daily, and 0.6 g/kg once daily in SCD patients
时间窗: Week 1 Day 1 (0.1 g/kg dose) and Week 2 Day 1 (0.3 g/kg dose. Week 3 Day 1 and Week4 Day1 (0.6 g/kg once daily dose)
PK (Tmax)
次要结局
- Effect of Food on L-glutamine Maximum Plasma Concentration (Cmax)(Week 1 Day 1, Week 2 Day 1, Week 4 Day 1.)
- L-glutamine Interpatient Variability of Area Under Curve (AUC)(Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.)
- Glutamate levels(Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.)
- Effect of Food on L-glutamine Area Under Curve (AUC)(Week 1 Day 1, Week 2 Day 1, Week 4 Day 1.)
- L-glutamine Dose Effect on Area Under Curve (AUC)(Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.)
- L-glutamine Interpatient Variability of Maximum Plasma Concentration (Cmax)(Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.)
- L-glutamine Dose Effect on Maximum Plasma Concentration (Cmax)(Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.)
- Ammonia levels(Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.)