A Double-Blind, Randomized, Crossover, Thorough QT/QTc Trial to Evaluate the Potential of Deferiprone to Prolong the QT Interval in Healthy Subjects
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- ApoPharma
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of 33 mg/kg Deferiprone
研究概览
简要总结
Randomized, single-dose, double-blind, placebo and active controlled, four-period crossover study to evaluate the effect of deferiprone on QTc prolongation after administration of a single therapeutic (33 mg/kg) and supratherapeutic(50 mg/kg) oral doses of deferiprone in healthy volunteers as compared to placebo treatment.
详细描述
Post-marketing study to evaluate the effect of deferiprone and deferiprone 3-O-glucuronide on QTc prolongation in healthy volunteers after administration of a single therapeutic (33 mg/kg) and supratherapeutic (50 mg/kg) oral dose of deferiprone and moxifloxacin (Avelox®).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adult males or females, 18 - 45 years of age (inclusive).
- •Body weight ≥ 50 kg.
- •Body mass index (BMI) ≥ 19 and ≤ 32 kg/m
- •Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical history, vital signs, physical examination).
- •Absolute neutrophil count (ANC) of >1.5x109/L.
- •12-lead ECGs which have no clinically significant findings as judged by the Principal Investigator (PI) or the PI's designee at screening and check-in of each study period,including:
- •Normal sinus rhythm (heart rate between 45 and 100 bpm);
- •QTcF interval ≤ 450 msec;
- •QRS interval ≤ 110 msec; and
- •PR interval ≤ 220 msec.
- •Subject must be capable of providing written informed consent, and must voluntarily consent to participate in the study.
- •Willing to answer inclusion and exclusion criteria questionnaire at check-in.
排除标准
- •History or presence of significant respiratory, cardiovascular, pulmonary, hepatic, renal, 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 products (e.g. cholecystectomy, resections of the small or large intestine, febrile conditions, chronic diarrhea, chronic vomiting, endocrine disease, severe infections,acute inflammations, etc.).
- •Presence of liver impairment: aspartate aminotransferase (AST), alanine aminotransferase (ALT) above the normal reference range.
- •Presence of significant kidney impairment: serum creatinine higher than the normal reference range.
- •Allergy to band aids, adhesive dressing or medical tape.
- •Clinically significant history or presence of ECG abnormalities such as second- or third-degree atrioventricular block; evidence, or family history, of prolonged QT syndrome.
- •Sustained sitting systolic blood pressure of <90 mmHg or >140 mmHg, or diastolic blood pressure of >95 mmHg at screening or check-in of Period
- •History or presence of hypersensitivity or idiosyncratic reaction to deferiprone, moxifloxacin, iron chelators, or quinolone antibiotics.
- •History or presence of:
- •agranulocytosis;
- •chronic bronchitis;
- •diabetes;
- •migraine;
- •hypertension;
- •hypotension;
- •hypokalemia;
- •seizures or epilepsy;
- •History or presence of alcoholism or drug abuse within the past 2 years.
- •Used tobacco/nicotine-containing product for at least 3 months prior to the first dose of study.
- •Used Depo-Provera® or levonorgestrel implant within 90 days prior to the first dose and throughout the study.
- •Participation in another clinical trial within 28 days prior to the first dose of the study.
- •Had a clinically significant illness during the 4 weeks prior to check-in on Day -1 of Period 1.
研究组 & 干预措施
Arm A - Maximum Therapeutic Dose
Single dose of 33 mg/kg rounded to the nearest 250 mg of deferiprone tablets
干预措施: Deferiprone (Drug)
Treatment Arm B - Supratherapeutic Dose
Single dose of 50 mg/kg rounded to the nearest 250 mg of deferiprone tablets
干预措施: Deferiprone (Drug)
Arm C - Placebo Control
Single dose of matching deferiprone and moxifloxacin placebo tablets.
干预措施: deferiprone matching placebo tablets (Drug)
Arm C - Placebo Control
Single dose of matching deferiprone and moxifloxacin placebo tablets.
干预措施: placebo (Drug)
Arm D - Positive Control
Single dose of one 400 mg moxifloxacin tablet.
干预措施: moxifloxacin (Drug)
结局指标
主要结局
Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of 33 mg/kg Deferiprone
时间窗: 24-hour interval
Change from baseline in QTcF interval was measured by looking at the post-dose difference in change from baseline in Fridericia's QT corrected heart rate (dQTcF) between treatment and placebo (ddQTcF) at each time interval. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose.
Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of 50 mg/kg Deferiprone
时间窗: 24-hour interval
Change from baseline in QTcF interval was measured by looking at the post-dose difference in change from baseline in Fridericia's QT corrected heart rate (dQTcF) between treatment and placebo (ddQTcF) at each time interval. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose.
Maximum Postdose QT/QTc Interval
时间窗: 24-hour interval
The maximum post-dose QT/QTc interval for deferiprone and placebo. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose.
Maximum Change From Baseline (dQT/dQTc)
时间窗: 24-hour interval
Maximum Change From Baseline (dQT/dQTc) for deferiprone and placebo. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose.
次要结局
- Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of Moxifloxacin(24-hour interval)
- Number of Participants With Adverse Events(From administration of the first dose until 7 days +/- 1 day following the final dose)
- Cmax of Deferiprone and Deferiprone 3-O Glucuronide(24-hour interval)
- Tmax of Deferiprone and Deferiprone 3-O-glucuronide(24-hour interval)
- AUC0-infinity for Serum Deferiprone and Deferiprone 3-O-glucuronide(24-hour interval)
- T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide(24-hour interval)