A Multiple-Center, Randomized, Double-blind, Multiple-Dose, Placebo-Controlled, Parallel-Group Study to Investigate the Safety, Tolerability, and Pharmacokinetics of RO0640796 (Oseltamivir) and Its Carboxylate Metabolite, RO0640802, Following Intravenous Administrations in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 99
- 主要终点
- Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hour (AUC0-12h) of Oseltamivir and RO0640802 at Steady State
研究概览
简要总结
This multi-center, randomized, double-blind, multiple-dose, placebo-controlled, parallel-group study will assess the safety and PK of oseltamivir (Tamiflu) and its carboxylate metabolite, RO0640802 in healthy participants. Participants will be randomized to receive 100 milligrams (mg) oseltamivir, 200 mg oseltamivir, or placebo, all administered intravenously twice daily (BID). The anticipated time on study treatment is 5 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- Double (Participant, Investigator)
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
- •Participants with Body Mass Index (BMI) 18-34 kilograms per meter square (kg/m^2), inclusive
- •Male participants who are willing to use barrier contraception for the duration of the study and for 3 months following the end of treatment
- •Female participants who are of non-child bearing potential
- •Female participants who are of child bearing potential utilizing two effective methods of contraception for the duration of the study and for 3 months following the end of treatment
排除标准
- •Evidence of clinically significant disease or disorder (for example, renal, cardiac, bronchopulmonary)
- •Any other condition or disease which would place the participant at undue risk, or interfere with the assessment, or with the ability of the participant to complete the study
- •Clinically significant orthostatic hypotension present at screening or history of clinically significant hypotensive episodes or symptoms of fainting, dizziness, or lightheadedness.
- •Participants with abnormal electrocardiogram (ECG), bradycardia or mean QTc at screening
- •Positive result for Hepatitis B, Hepatitis C, human immunodeficiency virus (HIV) 1 or 2 at screening
- •Renal impairment
- •Transplant recipients
- •A known clinically relevant history of allergy or hypersensitivity
- •Any clinically relevant abnormal laboratory test results
- •A clinically relevant history of abuse of alcohol or other drugs of abuse
- •Any major illness within 30 days prior to the screening examination
- •Smoking of more than 10 cigarettes a day or an equivalent amount of tobacco in the form of cigars or pipe
- •Participation in a clinical study with an investigational drug within 3 months prior to Day 1
- •Donation/loss of more than 500 milliliters (mL) of blood within 3 months prior to Day 1
- •Positive pregnancy test at screening or Day -1 and lactating women
研究组 & 干预措施
Oseltamivir 100 mg
Participants will receive 100 mg oseltamivir intravenous BID for 5 days.
干预措施: Oseltamivir (Drug)
Oseltamivir 200 mg
Participants will receive 200 mg oseltamivir intravenous BID for 5 days.
干预措施: Oseltamivir (Drug)
Placebo
Participants will receive oseltamivir matched placebo intravenous BID for 5 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hour (AUC0-12h) of Oseltamivir and RO0640802 at Steady State
时间窗: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 5
AUC is a measure of the plasma concentration of the drug over time. AUC is presented in nanogram times (\*) hour per milliliter (ng\*hour/mL). RO0640802 is the pharmacologically active carboxylate metabolite of oseltamivir.
Maximum Plasma Concentration (Cmax) of Oseltamivir and RO0640802 at Steady State
时间窗: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 5
Cmax is the maximum observed plasma concentration, presented in nanogram per milliliter (ng/mL). RO0640802 is the pharmacologically active carboxylate metabolite of oseltamivir.
次要结局
- Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Oseltamivir and RO0640802(Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1)
- Volume of Distribution (Vd) of Oseltamivir and RO0640802(Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5)
- Minimum Plasma Concentration (Cmin) of RO0640802(12-hour post dose on Day 1, 5 and predose on Day 2, 3, 4, 5)
- Area Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of Oseltamivir and RO0640802(Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5)
- Cmax of Oseltamivir and RO0640802(Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1)
- Time to Reach Maximum Plasma Concentration (Tmax) of Oseltamivir and RO0640802(Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5)
- Clearance (CL) of Oseltamivir and RO0640802(Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5)
- Half-Life (t1/2) of Oseltamivir and RO0640802(Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5)