A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Multiple Doses of ACH-0137171 in Subjects With Chronic Hepatitis C Infection
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 30
- 试验地点
- 10
- 主要终点
- To characterize the plasma pharmacokinetics of ACH-0137171 following administration of multiple, escalating, oral doses in subjects with chronic hepatitis C infection.
研究概览
简要总结
The purpose of this study was to investigate the safety, tolerability, pharmacokinetics (PK), and antiviral activity of multiple doses of ACH-0137171 in participants with chronic hepatitis C virus (HCV) infection.
详细描述
This was a randomized, double-blind, placebo-controlled, dose-escalation study of ACH-0137171 in participants with chronic HCV infection.
Sequential cohorts of 10 participants were randomized (8:2) to receive multiple doses of ACH-0137171 or placebo for 4 days (Days 1 through 4) with a single dose on Day 5 followed by a complete PK profile. Dosing was 300-600 milligrams (mg) administered either every 12 hours or every 6 hours (maximum daily dose of 2400 mg). All doses were administered with food.
The dose cohorts were as follows:
Study Schema:
Cohort 1: 300 mg ACH-0137171/placebo every 12 hours (600 mg/day) Cohort 2: 300 mg ACH-0137171/placebo every 6 hours (1200 mg/day) Cohort 3: 600 mg ACH-0137171/placebo every 6 hours (2400 mg/day)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic HCV infection must be documented by positive anti-HCV antibody using a third-generation enzyme immunoassay and persistent detection of HCV RNA in the blood for at least 6 months.
- •Participants must be infected with HCV genotype 1 (line probe assay; INNO-LiPA HCV II, Innogenetics) and maybe treatment-naïve or treatment-experienced (treatment experienced specifically means prior treatment with interferon, standard or pegylated, with or without ribavirin with therapy stopped > 6 months prior to screening).
- •Eligible participants must have had alanine aminotransferase and aspartate aminotransferase < 5 x upper limit of normal (ULN), plasma HCV RNA > 5 log10 international units (IU)/milliliter (mL), and have had no clinical or laboratory evidence of hepatic decompensation for inclusion (must have platelets > 100,000/cubic millimeter [mm^3], total bilirubin < 1.5 x ULN, prothrombin time < 1.5 x ULN, or albumin > 3.0 grams/deciliter [g/dL] for inclusion).
- •Women were eligible if not pregnant or breast-feeding.
- •Women of childbearing potential (that is, not surgically sterile or confirmed post menopausal) must have had confirmed negative pregnancy tests. All participants must practice a medically acceptable form of contraception.
排除标准
- •Human immunodeficiency virus or hepatitis B virus co-infection known cirrhosis.
- •Prior history of clinical hepatic decompensation (ascites, jaundice, encephalopathy, or variceal hemorrhage), alcoholic or other forms of chronic liver disease, evidence of hepatocellular carcinoma (α-fetoprotein > 50 nanograms/mL), creatinine clearance < 80 mL/minute (using Cockcroft-Gault equation), hemoglobin < 10 g/dL, neutrophils < 1500/mm^3, and abnormal thyroid function tests (thyroid stimulating hormone > 2.5 microIU/mL, free T4 > ULN), or, a positive test result for illicit drugs, alcohol, or drug abuse within the past 12 months.
- •Participants who have had significant gastrointestinal, thyroid, renal, cardiovascular, pulmonary, oncologic, or neurological disease, or who are currently receiving immunomodulators (corticosteroids), investigational, nephrotoxic or hepatotoxic drugs (for example, phenytoin, carbamazepine, isonicotinic acid hydrazide, azole anti-fungal agents such as ketoconazole, and aminoglycoside antibiotics), non-steroidal anti-inflammatory agents, ibuprofen or acetaminophen (on a daily basis) will also be excluded.
结局指标
主要结局
To characterize the plasma pharmacokinetics of ACH-0137171 following administration of multiple, escalating, oral doses in subjects with chronic hepatitis C infection.
To assess the short-term safety and tolerability of multiple, escalating, oral doses of ACH-0137171 in subjects with chronic hepatitis C infection.
To assess the antiviral activity of ACH-0137171 as measured by plasma HCV RNA levels in subjects with chronic hepatitis C infection following administration of multiple, escalating, oral doses.
To assess the correlation between antiviral activity and pharmacokinetic parameters.
次要结局
- To perform viral dynamic and pharmacodynamic modeling of ACH 0137171 virologic response.
- To assess the biochemical response of ACH-0137171 as measured by the change from baseline of serum ALT and AST levels.