Phase 1 Pharmacokinetic and Pharmacodynamic Responses to Oral L-Citrulline in Patients With Sickle Cell Disease
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- PK and PD responses to L-citrulline
研究概览
简要总结
To evaluate PK and PD responses to L-citrulline given orally for four weeks to patients with sickle cell disease who are otherwise healthy.
详细描述
Phase 1, single center, open label, multiple-dose study consisting of a screening period followed by four weeks of treatment. At least 12 male and female patients, 10 years of age or older, with sickle cell disease but otherwise healthy, will be enrolled in the study.
PK measurements include plasma concentrations of L-citrulline, L-arginine, L-ornithine, and L-proline following the first dose of orally administered L-citrulline and after four weeks of twice daily administration of the drug.
PD measurements include intercellular and vascular adhesion molecules (ICAM, VCAM, and E-selectin), surrogate markers of sickle cell disease activity, and PAT, a measurement of vascular function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, 10 years of age or older on the day of dosing, and generally healthy as determined by medical history, physical examination, and laboratory test values
- •Diagnosis of sickle cell anemia (Hb SS)
- •For female of child-bearing potential, a negative serum pregnancy test and using an adequate method of contraception
- •Has signed and received a copy of the written informed consent form approved by the investigator's Institutional Review Board (IRB), understands the purposes and risks of the study and agrees to follow the restrictions and schedule of procedures as defined by this protocol
排除标准
- •History of sickle-cell-related pain crisis within two weeks of study
- •Pregnant or breast feeding
- •Transfusion within last 90 days
- •Creatinine >1.5 X upper limit of normal
- •SGPT > 2 X upper limit of normal
- •History of allergic reaction to arginine or citrulline product
- •Requires chronic medication other than study drug that cannot be discontinued during the study period
- •Unable to take or tolerate oral medications
- •Unreliable venous access
- •Noncompliant with regular care
- •Participation in an investigational drug or medical device study within previous 30 days
- •In the opinion of the investigator is not a good candidate for participation in the study
结局指标
主要结局
PK and PD responses to L-citrulline
Endpoints will be determined as change from baseline
次要结局
- Assessment of safety and tolerability of L-citrulline,