An Open-label Study to Compare the Pharmacokinetic Profiles of a Single Dose of Ferriprox in Subjects With Impaired Renal Function and Healthy Volunteers
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- ApoPharma
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
研究概览
简要总结
Multi-center, non-randomized, open-label, single-dose, parallel group study to determine the effect of impaired renal function on the PK of deferiprone and its 3-O-glucuronide metabolite following a single oral dose of 33mg/kg Ferriprox®.
详细描述
Post-marketing study to evaluate the effect of impaired renal function on the pharmacokinetics (PK) of deferiprone and its 3-O-glucuronide metabolite and on the safety of Ferriprox® in subjects with mild, moderate and severe renal impairment as compared to healthy volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All subjects:
- •Adult males or females, 18 - 75 years of age (inclusive);
- •Body weight ≥ 45 kg;
- •Body mass index (BMI) range of approximately 18.5-32 kg/m^2 (inclusive);
- •Absolute neutrophil count (ANC) of >1.5x10^9/L;
- •Healthy volunteers:
- •Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical history, vital signs, physical examination);
- •eGFR ≥ 90 mL/min/1.73m^2;
- •Renally impaired subjects:
- •Considered clinically stable in the opinion of the Investigator;
- •Subjects with mild renal impairment (eGFR 60-89 mL/min/1.73m^E2) OR moderate renal impairment (eGFR 30-59 mL/min/1.73m^2) OR severe renal impairment (eGFR 15-29 mL/min/1.73m^2).
排除标准
- •History of renal transplant;
- •Subjects undergoing any method of dialysis;
- •History or presence of clinically unstable significant respiratory, cardiovascular, pulmonary, hepatic, renal (except for subjects assigned to one of the renally impaired groups), hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease;
- •Disorders or surgery of the gastrointestinal tract which may interfere with drug absorption or may otherwise influence the PK of the investigational medicinal product (e.g. cholecystectomy, resections of the small or large intestine, febrile conditions, chronic diarrhea, chronic vomiting, endocrine disease, severe infections, acute inflammations, etc.);
- •Clinically significant abnormalities on 12-lead ECG (e.g., QTcF≥430 ms in males or ≥450 ms in females);
- •Evidence of liver damage: hepatitis B and C; aspartate aminotransferase (AST), alanine aminotransferase (ALT) that is considered clinically significant by the Investigator;
- •Participation in another clinical trial within 28 days prior to the study drug administration;
研究组 & 干预措施
Normal renal function
Healthy volunteers, defined as having an estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone.
干预措施: Deferiprone (Drug)
Mild Renal Impairment
Mild impairment, defined as having an eGFR 60-89 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone.
干预措施: Deferiprone (Drug)
Moderate Renal Impairment
Mild impairment, defined as having an eGFR 30-59 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone.
干预措施: Deferiprone (Drug)
Severe Renal Impairment
Severe impairment, defined as having an eGFR 15-19 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone.
干预措施: Deferiprone (Drug)
结局指标
主要结局
Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
时间窗: 24-hour interval
Cmax was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in subjects with normal, mild, moderate and severe renal impairment. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose.
Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
时间窗: 24 hour interval
Tmax was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose. The results of the Tmax parameter are reported as the median and range (other parameters are reported as mean and standard deviation).
AUC Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide
时间窗: 24 hour interval
AUC0-∞ was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose.
T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide
时间窗: 24 hour interval
T1/2 was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose.
Ae24 for Urine Deferiprone and Deferiprone 3-O-glucuronide
时间窗: 24 hour interval
Ae24 (the amount excreted in urine from time zero to 24 hours) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Urine samples were collected at the intervals of -2 to 0 hours pre-dose and 0 to 2, 2 to 4, 4 to 8, 8 to 12, and 12 to 24 hours post-dose.
Fe24 for Serum Deferiprone and Deferiprone 3-O-glucuronide
时间窗: 24-hour interval
Fe24 (fraction of dose excreted in urine from time zero to 24 hours) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Urine samples were collected at the intervals of -2 to 0 hours pre-dose and 0 to 2, 2 to 4, 4 to 8, 8 to 12, and 12 to 24 hours post-dose. Some of the Fe24 values were over 100% which could be explained by variability in urine collection (e.g. incomplete collection of urine into the container) and volume measurement, as well as analytical imprecision.
次要结局
- Safety and Tolerability of Ferriprox® in Subjects With Renal Impairment.(From time of dosing until 72 hours post-dose)