A Phase 2, 2-panel, Open-label Randomized Study in Hepatitis C Virus Infected Subjects to Investigate the Pharmacokinetic Interactions Between Simeprevir and Ledipasvir in a Treatment Regimen Consisting of Simeprevir, Sofosbuvir and Ledipasvir in Treatment-naive Participants.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 41
- 主要终点
- Maximum Plasma Concentration (Cmax) of Simeprevir
研究概览
简要总结
The purpose of this study is to evaluate the pharmacokinetic interactions between simeprevir and ledipasvir in a treatment regimen consisting of simeprevir (SMV), sofosbuvir (SOF), and ledipasvir (LDV) in treatment-naive participants with chronic hepatitis C virus (HCV) genotype 1 infection.
详细描述
This is an open-label (all people know the identity of the intervention), 2-panel, Phase 2, randomized (study medication assigned to participants by chance) study. The study will consist of 3 study phases: Screening Phase (5 weeks), an Open-label Treatment Phase (70 days for Panel 1 and 56 days for Panel 2), a Post-treatment Follow-up Phase (12 weeks after the actual end of treatment). Participants will receive a combination of the following treatments: Treatment A: SMV 150 milligram (mg) once daily; Treatment B: LDV 90 mg along with SOF 400 mg once daily; Treatment C: SOF 400 mg once daily. Participants will be randomly assigned to Panel 1 (Treatment AC followed by Treatment AB) and Panel 2 (Treatment B followed by Treatment AB). The total study duration will be approximately 27 weeks for participants in Panel 1 and 25 weeks for participants in Panel 2. Participants will be primarily accessed for pharmacokinetic parameters. Participants' safety will be monitored throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with Body Mass Index (weight in kilogram [kg] divided by the square of height in meters) of 18.0 to 35.0 kilogram per square meter kg/m^2, extremes included
- •Participants must be treatment-naive (that is, have not received prior treatment with any approved or investigational drug)
- •Participants with HCV ribonucleic acid (RNA) plasma levels greater than (>) 10,000 international unit per milliliter (IU/ml) and lower than 6,000,000 international unit per milliliter (IU/ml) at screening
- •Participants with absence of cirrhosis confirmed by FibroTest/Fibrosure score less or equal to 0.75 and an aspartate aminotransferase to platelet ration index less or equal to 2 or a Fibroscan less or equal to 14.6 kilopascale (kPA), performed within 6 months prior or during the screening period
- •Participants with documented chronic HCV infection: diagnosis of HCV infection >6 months prior to screening, either by detectable HCV RNA, an HCV positive antibody test or presence of histological changes consistent with chronic hepatitis in a liver biopsy
排除标准
- •Participant has infection/co-infection with HCV of a genotype other than genotype 1, human immunodeficiency virus (HIV) type 1 or 2
- •Participant has any evidence of liver disease of non-HCV etiology. This includes, but is not limited to acute hepatitis A, active hepatitis B, drug- or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or any other non-HC liver disease considered clinically significant by the investigator
- •Participant with significant co-morbidities, conditions or clinical significant findings during screening assessments that in the opinion of the investigator could compromise the participants' safety or could interfere with the Participant participating in and completing the study
- •Participant received an organ transplant (other than cornea or hair transplant or skin graft)
- •Participants have key protocol defined laboratory abnormalities
研究组 & 干预措施
Panel 1
Participants will receive Simeprevir (SMV) 150 milligram (mg) capsule (Treatment A) along with Sofosbuvir (SOF) 400 mg tablet, orally, once daily (Treatment C) from Day 1 until Day 14 followed by SMV 150 mg capsule (Treatment A) along with fixed dose combination (FDC) tablet of 90 mg Ledipasvir (LDV)/400 mg SOF (Treatment B), orally, once daily from Day 15 until Day 70.
干预措施: Ledipasvir (LDV) (Drug)
Panel 1
Participants will receive Simeprevir (SMV) 150 milligram (mg) capsule (Treatment A) along with Sofosbuvir (SOF) 400 mg tablet, orally, once daily (Treatment C) from Day 1 until Day 14 followed by SMV 150 mg capsule (Treatment A) along with fixed dose combination (FDC) tablet of 90 mg Ledipasvir (LDV)/400 mg SOF (Treatment B), orally, once daily from Day 15 until Day 70.
干预措施: Simeprevir (SMV) (Drug)
Panel 2
Participants will receive FDC tablet of 90 mg LDV/400 mg SOF (Treatment B), orally, once daily from Day 1 until Day 14 followed by SMV 150 mg capsule (Treatment A) along with FDC tablet of 90 mg LDV/400 mg SOF (Treatment B), orally, once daily from Day 15 until Day 56.
干预措施: Ledipasvir (LDV) (Drug)
Panel 2
Participants will receive FDC tablet of 90 mg LDV/400 mg SOF (Treatment B), orally, once daily from Day 1 until Day 14 followed by SMV 150 mg capsule (Treatment A) along with FDC tablet of 90 mg LDV/400 mg SOF (Treatment B), orally, once daily from Day 15 until Day 56.
干预措施: Sofosbuvir (SOF) (Drug)
Panel 2
Participants will receive FDC tablet of 90 mg LDV/400 mg SOF (Treatment B), orally, once daily from Day 1 until Day 14 followed by SMV 150 mg capsule (Treatment A) along with FDC tablet of 90 mg LDV/400 mg SOF (Treatment B), orally, once daily from Day 15 until Day 56.
干预措施: Simeprevir (SMV) (Drug)
Panel 1
Participants will receive Simeprevir (SMV) 150 milligram (mg) capsule (Treatment A) along with Sofosbuvir (SOF) 400 mg tablet, orally, once daily (Treatment C) from Day 1 until Day 14 followed by SMV 150 mg capsule (Treatment A) along with fixed dose combination (FDC) tablet of 90 mg Ledipasvir (LDV)/400 mg SOF (Treatment B), orally, once daily from Day 15 until Day 70.
干预措施: Sofosbuvir (SOF) (Drug)
结局指标
主要结局
Maximum Plasma Concentration (Cmax) of Simeprevir
时间窗: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
The Cmax is the maximum observed plasma concentration.
Minimum Plasma Concentration (Cmin) of Simeprevir (SMV)
时间窗: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
The Cmin is the minimum observed plasma concentration.
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Simeprevir
时间窗: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.
Minimum Plasma Concentration (Cmin) of Ledipasvir (LDV)
时间窗: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
The Cmin is the minimum observed plasma concentration.
Maximum Plasma Concentration (Cmax) of Ledipasvir
时间窗: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
The Cmax is the maximum observed plasma concentration.
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Ledipasvir
时间窗: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
AUCtau is defined as area under the analyte concentration versus time curve during dosing interval tau, calculated by linear-linear trapezoidal summation.
次要结局
- Average Plasma Concentration at Steady State (Cavg,ss) of Simeprevir(Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28)
- Fluctuation Index (FI) of Simeprevir(Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28)
- Trough Plasma Concentration (Ctrough) of Ledipasvir(Pre-dose on Day 14 and Day 28)
- Time to Reach Maximum Plasma Concentration (Tmax) of Ledipasvir(Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28)
- Trough Plasma Concentration (Ctrough) of Simeprevir(Pre-dose on Day 14 and Day 28)
- Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir(Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28)
- Average Plasma Concentration at Steady State (Cavg,ss) of Ledipasvir(Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28)
- Fluctuation Index (FI) of Ledipasvir(Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2)
- Percentage of Participants With On-treatment Virologic Response(Week 1, up to EOT (Week 10 in Panel 1 and Week 8 in Panel 2))
- Number of Participants Not Achieving Sustained Virologic Response (SVR) Showing Emerging Mutation in HCV Nonstructural Protein 3/4A (NS3/4A), Nonstructural Protein 5A (NS5A), and Nonstructural Protein 5B (NS5B) Sequence(Up to end of follow-up phase (Week 12 of follow-up phase) in Panel 1 and Panel 2)
- Percentage of Participants With Sustained Virologic Response (SVR) 4 Weeks After the Actual EOT (SVR4) and 12 Weeks After the Actual EOT (SVR12)(4 weeks after EOT (Week 4 of follow-up phase in Panel 1 and Panel 2) and 12 weeks after EOT (Week 12 of follow-up phase in Panel 1 and Panel 2))
- Percentage of Participants With On-treatment Failure(Day 70 in Panel 1 and Day 56 in Panel 2)
- Percentage of Participants With Viral Relapse(Up to Week 12 follow-up phase after EOT)