A Single Center, Phase I, Double-blind, Placebo-controlled Evaluation of the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of Deferiprone Administered by Intravenous Infusion to Healthy Male and Female Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- ApoPharma
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Area Under the Curve From Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide
研究概览
简要总结
Single center, randomized, double-blind, placebo-controlled, adaptive sequential ascending-dose study for the evaluation of the safety, tolerability, and pharmacokinetics of single doses of deferiprone administered by intravenous infusion to healthy males and females. A bioavailability comparison will be included.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adult males or females, at least 18 years old but not older than 50 years.
- •Body weight at least 60kg.
- •Body Mass Index (BMI) ≥ 18.50 and ≤ 30.00 kg/m2
- •Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical history, ECG, vital signs, physical examination.
- •Non or ex-smoker (someone who has completely stopped smoking 6 months before study start)
- •For females, negative result on a serum pregnancy test.
排除标准
- •Absolute neutrophil count (ANC) <1.5x10^9/L.
- •History or presence of hypersensitivity to deferiprone or any related products.
- •History or presence of gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs.
- •Presence of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, endocrine, immunologic or dermatologic disease.
- •Any history of tuberculosis (TB) or prophylaxis for TB.
- •Suicidal tendency, history of seizures, head trauma with coma or craniotomy/trepanation, state of confusion or relevant psychiatric disease.
- •Inadequate venous access in either arm.
- •Presence of out-of-range cardiac interval or clinically significant ECG abnormalities (PR <110 msec or > 220 msec, QRS <60 msec or >119 msec, QTcB > 450 msec for males and >460 msec for females).
- •Use of acetaminophen, acetylsalicylic acid (ASA), or non-steroidal anti-inflammatory drugs (NSAIDs) in the previous 7 days before study start.
- •Use of any enzyme-modifying drugs, including strong inhibitors of P450 (CYP) enzymes such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem, and HIV antivirals OR strong inducers of CYP enzymes such as: barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin, and St. John's wart within 28 days prior to study start.
- •Maintenance therapy with any drug, or significant history of drug dependency or alcohol abuse.
- •Had a clinically significant illness during the 28 days prior to study start.
- •Receipt of an investigational product in another clinical trial within 28 days prior prior to study start.
- •Enrolment in a previous cohort of this study.
研究组 & 干预措施
Cohort 1
Single dose of 500mg deferiprone or placebo administered via intravenous infusion.
First 2 subjects to enroll: 1 will be randomized to receive deferiprone and the other to receive placebo.
Next 14 subjects enrolled: 13 will be randomized to receive deferiprone and 1 to receive placebo.
干预措施: Deferiprone (Drug)
Cohort 1
Single dose of 500mg deferiprone or placebo administered via intravenous infusion.
First 2 subjects to enroll: 1 will be randomized to receive deferiprone and the other to receive placebo.
Next 14 subjects enrolled: 13 will be randomized to receive deferiprone and 1 to receive placebo.
干预措施: Placebo (Drug)
Cohort 2
Single dose of 1000mg deferiprone or placebo administered via intravenous infusion and oral solution.
Randomization will be done for all 16 subjects at the same time: 14 will be randomized to receive deferiprone and 2 to receive placebo.
Subjects enrolled to cohort 2 will receive an oral dose of deferiprone.
干预措施: Deferiprone (Drug)
Cohort 2
Single dose of 1000mg deferiprone or placebo administered via intravenous infusion and oral solution.
Randomization will be done for all 16 subjects at the same time: 14 will be randomized to receive deferiprone and 2 to receive placebo.
Subjects enrolled to cohort 2 will receive an oral dose of deferiprone.
干预措施: Placebo (Drug)
Cohort 3
Single dose of 1500mg deferiprone or placebo administered via intravenous infusion.
Randomization will be done for all 16 subjects at the same time, 14 will be randomized to receive deferiprone and 2 to receive placebo.
干预措施: Deferiprone (Drug)
Cohort 3
Single dose of 1500mg deferiprone or placebo administered via intravenous infusion.
Randomization will be done for all 16 subjects at the same time, 14 will be randomized to receive deferiprone and 2 to receive placebo.
干预措施: Placebo (Drug)
Cohort 4
Single dose of 2000mg deferiprone or placebo administered via intravenous infusion.
First 2 subjects to enroll: 1 will be randomized to receive deferiprone and the other to receive placebo.
Next 14 subjects enrolled: 13 will be randomized to receive deferiprone and 1 to receive placebo.
干预措施: Deferiprone (Drug)
Cohort 4
Single dose of 2000mg deferiprone or placebo administered via intravenous infusion.
First 2 subjects to enroll: 1 will be randomized to receive deferiprone and the other to receive placebo.
Next 14 subjects enrolled: 13 will be randomized to receive deferiprone and 1 to receive placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Area Under the Curve From Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide
时间窗: 14-hour interval
AUC0-∞ was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.
Maximum Measured Serum Concentration (Cmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide
时间窗: 14-hour interval
Cmax was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.
Time to Maximum Observed Serum Concentration (Tmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide
时间窗: 14-hour interval
Tmax was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 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).
The Terminal Elimination Half-life (T1/2el) for Serum Deferiprone and Deferiprone 3-O-glucuronide
时间窗: 14-hour interval
T1/2el was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.
Safety and Tolerability of Single Ascending Doses of Deferiprone When Administered by Intravenous Infusion in Healthy Volunteers.
时间窗: From start of intravenous dosing until Day 5 post-dose for all subjects; and from time of oral dose until 24 hours post-dose for subjects who additionally received oral deferiprone
The number of participants who experienced adverse events (including any changes of clinical significance in physical examinations, vital signs, 12-lead ECG, and clinical laboratory tests) following a single dose of intravenous deferiprone.
次要结局
- Safety and Tolerability of a Single 1000 mg Oral Dose of Deferiprone(From dosing until 24 hours post-dose)
- Comparison of Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide Between Deferiprone for Infusion and Oral Deferiprone(14-hour interval)
- Absolute Bioavailability of Deferiprone(14-hour interval)