A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Multicenter Study to Assess the Efficacy and Safety of Rifaximin Soluble Solid Dispersion (SSD) Tablets Plus Lactulose for the Treatment of Overt Hepatic Encephalopathy (OHE)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 71
- 试验地点
- 34
- 主要终点
- Time to Overt Hepatic Encephalopathy (OHE) Resolution Determined Using the Hepatic Encephalopathy Grading Instrument (HEGI), Defined as HEGI Score < 2
研究概览
简要总结
Study to Assess the Efficacy and Safety of Rifaximin Soluble Solid Dispersion (SSD) Tablets Plus Lactulose for the Treatment of Overt Hepatic Encephalopathy (OHE).
详细描述
The primary objective of this study is to assess the efficacy of rifaximin SSD plus lactulose versus placebo plus lactulose for the treatment of overt hepatic encephalopathy (OHE). The secondary objectives of this study are to assess the safety of rifaximin SSD in subjects with OHE and to assess the effects of treatment with rifaximin SSD on key secondary endpoints.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Blinding will be maintained in the QD SSD cohorts by administering placebo as the second daily dose.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female age 18 to 75 years of age (inclusive) at the time of screening.
- •Females of childbearing potential, defined as a female who is fertile following menarche, must have a negative serum pregnancy test at screening and agree to use an acceptable method of contraception throughout their participation in the study.
- •Note: Female subjects who have been surgically sterilized (e.g., hysterectomy or bilateral tubal ligation) or who are postmenopausal (defined as total cessation of menses for > 1 year) will not be considered "female subjects of childbearing potential".
- •Subject is hospitalized with liver cirrhosis and/or OHE and has a confirmed diagnosis of OHE at Baseline.
- •Subject has a Grade 2 or Grade 3 HE episode according to the HE Grading Instrument (HEGI) following 8 to 12 hours of intravenous (IV) hydration and lactulose treatment.
排除标准
- •Subject has an uncontrolled major psychiatric disorder including major depression or psychoses as determined by the investigator.
- •Subject has been diagnosed with an infection for which they are currently taking oral or parenteral antibiotics, which cannot be discontinued at time of enrollment. Note: Subjects currently taking Rifaximin are not excluded
- •Subject shows presence of intestinal obstruction or has inflammatory bowel disease.
- •Subject has uncontrolled Type 1 or Type 2 diabetes. Note: Subjects with controlled diabetes may be enrolled if they are on stable doses of oral hypoglycemic drugs for at least 3 months prior to screening, and demonstrate clinically acceptable blood glucose control at Baseline, as determined by the investigator.
- •Subject has an active malignancy (exceptions: non-melanoma skin cancers).
研究组 & 干预措施
Cohort 1 40 mg Rifaximin SSD once daily
40 mg Rifaximin immediate release (IR) rifaximin SSD once daily (QD) and lactulose
干预措施: 40 mg Rifaximin SSD once daily (Drug)
Cohort 2 40 mg Rifaximin SSD twice daily
40 mg Rifaximin immediate release (IR) rifaximin SSD twice daily (BID) and lactulose
干预措施: 40 mg Rifaximin SSD twice daily (Drug)
Cohort 3 80 mg Rifaximin SSD once daily
80 mg Rifaximin sustained extended release (SER) rifaximin SSD once daily (QD) and lactulose
干预措施: 80 mg Rifaximin SSD once daily (Drug)
Cohort 4 80 mg Rifaximin SSD twice daiy
80 mg Rifaximin sustained extended release (SER) rifaximin SSD twice daily (BID) and lactulose
干预措施: 80 mg Rifaximin SSD twice daily (Drug)
Cohort 5 Placebo twice daily
SSD placebo twice daily (BID) and lactulose
干预措施: Placebo (Drug)
结局指标
主要结局
Time to Overt Hepatic Encephalopathy (OHE) Resolution Determined Using the Hepatic Encephalopathy Grading Instrument (HEGI), Defined as HEGI Score < 2
时间窗: 14 days
A participant was considered to have an overt HE episode if at least one of the following applied: (1) Disorientated to time or place or person, (2) Lethargic and has asterixis, (3) Inability to assess the patient due to disorientation to time and place and person; and/or somnolence, and/or coma. Severity of OHE episodes was graded using the HEGI scale, where Grade 1 is no clinical findings of OHE, and Grade 4 is comatose. Higher scores on the scale have higher severity (worse outcome).
次要结局
- Time to Improvement in Hepatic Encephalopathy Grading Instrument (HEGI) Score, Defined as at Least One Grade Decrease (Improvement)(14 days)
- Time to Hospital Discharge(14 days)