A Prospective Open Label, Pharmacokinetic Study of an Oral Hydroxyurea Solution in Children With Sickle Cell Anemia.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 6
- 主要终点
- Clearance (CL/F)
研究概览
简要总结
An open label, safety and pharmacokinetic study of oral hydroxyurea solution administered to children from 6 months to 17.99 years (i.e. to the day before 18th birthday), with a 12 to 15 month treatment period for each participant. The study treatment duration will be for 6 months at the maximum tolerated dose [MTD], which is usually reached by 6 months after initiation of treatment. For patients in whom time to MTD is longer than 6 months or not achieved at all, the maximum duration of study treatment will be 15 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged from 6 months to 17.99 years of age (i.e. to the day before 18th birthday).
- •Diagnosis of sickle cell anemia (HbSS and HbSβº).
- •Parent(s)/legal guardian able and willing to provide written informed consent for the child to take part in the study.
- •Where applicable, the child should assent to undergo blood sampling for pharmacokinetic and biochemistry purposes and to allow physiological measurements to be made.
排除标准
- •Any clinically significant medical condition or abnormality, which, in the opinion of the Investigator, might have compromised the safety of the patient or which might have interfered with the study.
- •Hydroxyurea use within 6 months before enrolment.
- •Renal insufficiency (known creatinine more than twice the upper limit of normal (ULN) for age and >1.0 mg/dL [88.4 μmol/L]).
- •Clinical evidence of hepatic compromise with alanine aminotransferase (ALT) >3 times the ULN (a temporary swing in ALT did not result in exclusion).
- •Other significant organ system dysfunction based on the site Investigators discretion.
- •Severe active infections: fungal, viral or bacterial (as confirmed by culture), examples included tuberculosis, malaria, active hepatitis, osteomyelitis or any other illness that would have precluded the use of HU in normal clinical practice.
- •Active chronic leg ulcers.
- •Known allergy to oral HU solution or any of the excipients.
- •Positive pregnancy test for females of child-bearing potential (in post-menarcheal females) before initiation of treatment, unless participant was sexually abstinent. Note: True abstinence was considered as being in line with the preferred and usual lifestyle of the participant. Periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- •Inadequate contraception measures in sexually active females (post-menarcheal females) and males of child-bearing age (see Section 9.5.1.10.4).
- •Breastfeeding at study initiation.
- •Participation in another clinical trial of an IMP.
- •Known infection with HIV.
研究组 & 干预措施
Open Label
Novel oral solution formulation of hydroxyurea
干预措施: Oral Hydroxyurea (100 mg/mL) Solution (Drug)
结局指标
主要结局
Clearance (CL/F)
时间窗: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36)
Model estimated Pharmacokinetic Parameter (PK population: n=32, having received at least one dose of study drug).
Volume of Distribution (V/F)
时间窗: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36)
Model estimated Pharmacokinetic Parameter (PK population: n=32, having received at least one dose of study drug).
Time to Maximum Concentration (Tmax)
时间窗: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36)
Mean Tmax (h) pharmacokinetic parameter derived using the final population PK model.
Maximum Plasma Concentration Cmax (ug/mL)
时间窗: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36)
Mean Cmax (ug/mL) pharmacokinetic parameter derived using the final population PK model.
Area Under Plasma Concentration Time Curve (AUC 0-Inf)
时间窗: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36)
Mean AUC 0-Infinity (hr\*ug/mL) pharmacokinetic parameters derived using the final population PK model.
Terminal Half-life (Hours)
时间窗: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36)
Mean Terminal Half-life (hours) pharmacokinetic parameter derived using the final population PK model.
次要结局
- Adverse Events(Screening Up to Week 64)
- Absolute Neutrophil Count (ANC)(Baseline and Week 60 (or final visit); max 15 months on treatment)
- White Blood Cell Count (Leukocytes)(Baseline to Week 60 or Final Visit; max 15 months on treatment)
- Platelets(Baseline to Week 60 (or Final Visit), max 15 months on treatment)
- Mean Corpuscular Hemoglobin (MCH)(Baseline to Week 60 (or Final Visit), max 15 months on treatment)
- Hematocrit(Up to Week 60)
- Bilirubin(Up to Week 60)
- Elevation in Liver Function Tests (LFTs)(Up to Week 60)
- Hemoglobin(Baseline to Week 60 (or Final Visit); max 15 months on treatment)
- Bacterial Infections(Up to Week 60)
- Leg Ulcers(Up to Week 60)
- Fetal Hemoglobin(Baseline to Week 60 (or Final Visit); max 15 months on treatment)
- Viral Infections(Up to Week 60)
- Fungal Infections(Up to Week 60)
- Mean Corpuscular Volume (MCV)(Baseline to Week 60 (or Final Visit); max 15 months on treatment)
- Cystatin C(PK1 (day 1), week 20-32 (6 months) and Week 60 (Final Visit))
- Incidence of Acute Vaso-Occlusive Pain Crises (VOC)(12 months prior to treatment and time-averaged 12 months post-treatment; maximum 15 months on IMP)
- Number and Frequency of Blood Transfusions(Up to Week 60)
- Acute Chest Syndrome (ACS)(12 months prior to treatment and time averaged 12 months post-treatment; maximum 15 months on IMP)
- Hospitalizations(12 months prior to treatment and time-averaged 12 months post-treatment; maximum 15 months on IMP)
- Dose Escalation i.e. Maximum Tolerated Dose (MTD)(Screening Up to Final Visit (Week 60 or Withdrawal), maximum 15 months on IMP)
- Other SCA-related Hospitalizations(12 months prior to treatment and time averaged 12 months post-treatment; maximum 15 months on IMP)
- Parent/Caregiver Palatability and Acceptability Questionnaire(Taken once at any point after 8 weeks on study medication (or at early Withdrawal))
- Vitamin D(From Screening Up to Final Visit (Week 60 or WD))
- Other Non-SCA-related Hospitalizations(12 months prior to treatment and 12 months post-treatment; maximum 15 months on IMP)