A Study to Evaluate the Bioequivalence of Orfadin Suspension 4 mg/mL Compared to Orfadin Capsules 10 mg, and the Effect of Food on the Bioavailability of the Suspension. An Open-label, Randomized, Cross-over, Single-dose Study in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- The Area Under the Serum Concentration Curve (AUC) During 72 Hours After Dose (AUC72h) During Fasting Conditions.
研究概览
简要总结
The study is primarily being performed in order to demonstrate bioequivalence between the Orfadin (nitisinone) suspension and the marketed capsule formulation. The study will also contain a comparison of the bioavailability of the suspension given with food and on an empty stomach.
详细描述
This is an open, randomized 3-way crossover study in 12 healthy volunteers. Subjects will receive single oral 30-mg doses of nitisinone as a suspension (fasting and with food) and as hard gelatin capsules (fasting only). There will be a 2-week washout period between the doses.
There will be a screening visit within 3 weeks prior to the first dose. During each treatment period, subjects will be admitted to the clinic from the afternoon on the day before drug administration (i.e., on Day -1) and remain at the clinic until the 48-hour post-dose blood sample has been collected in the morning of Day 3. They will then return for ambulatory visit in the morning of Day 4 (72-hour sample). A follow-up visit will take place 7-14 days after the last dose.
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
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male volunteers
- •Age: 18-55 years, inclusive
- •BMI: 18,5-30,0 kg/m2, inclusive
排除标准
- •heavy smokers
- •Consumption of more than 4 cups of coffee per day.
- •History of drug and/or alcohol abuse.
- •Positive drug screen or alcohol breath test.
- •Positive screens for hepatitis B surface antigen, hepatitis C antibodies and human immunodeficiency virus (HIV) 1-2 antibodies.
- •Enrollment in another concurrent clinical study
- •Intake of an investigational medicinal product within three months prior to inclusion in this study.
- •Donation of more than 50 mL of blood within 60 days prior to drug administration
- •Donation of more than 1,5 liters of blood in the 10 months prior to first drug administration.
研究组 & 干预措施
Orfadin capsules, fasting
Orfadin capsules, single dose, 30 mg
干预措施: Nitisinone, capsule (Drug)
Orfadin suspension, fasting
Orfadin suspension 4 mg/mL, single dose 30 mg (7,5 mL)
干预措施: Nitisinone, suspension (Drug)
Orfadin suspension, with food
Orfadin suspension 4mg/mL, single dose 30 mg (7,5 mL)
干预措施: Nitisinone, suspension (Drug)
结局指标
主要结局
The Area Under the Serum Concentration Curve (AUC) During 72 Hours After Dose (AUC72h) During Fasting Conditions.
时间窗: Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.
The Maximum Serum Concentration (Cmax) During Fasting Conditions.
时间窗: Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.
次要结局
- The Area Under the Serum Concentration Curve (AUC) During 72 Hours After Dose (AUC72h)(Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.)
- The Maximum Serum Concentration (Cmax)(Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.)
- AUC From Time Zero to Infinity(Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.)
- Time to Reach C-Max (t-Max)(Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.)
- Terminal Half-life(Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.)
- Oral Clearance (CL/F)(Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.)
- Apparent Volume of Distribution (Vz/F)(Day 1 predose and at 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours postdose.)