An Open-Label, Single-Dose, Parallel-Group, Two-Part Study to Evaluate the Pharmacokinetics and Safety of Risdiplam in Subjects With Mild or Moderate Hepatic Impairment Compared to Subjects With Normal Hepatic Function

Hoffmann-La Roche3 个研究点分布在 1 个国家目标入组 26 人开始时间: 2019年5月16日最近更新: 2021年2月21日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Hoffmann-La Roche
入组人数: 26
试验地点: 3
主要终点: Part 1: Maximum Observed Plasma Concentration (Cmax) of Risdiplam and M1

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a multi-center, open-label, non-randomized, parallel-group, 2-part study to evaluate the effect of hepatic impairment on the PK and safety and tolerability of a single oral dose of risdiplam compared to matched healthy participants with normal hepatic function.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Treatment
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: 是

入选标准

•All Participants:
•BMI between 18.0 and 36.0 kilograms per square metre (kg/m2), inclusive, and body weight > / = 50 kg
•Females must not be pregnant or lactating and must be of non-childbearing potential
•Male participants (whether surgically sterilized or not) with female partners of childbearing potential must use methods of contraception from Screening until 4 months after their dose of the study drug as detailed in the protocol
•Male participants must not donate sperm from Check-in (Day -1) until 4 months after their dose of the study drug
•Participants with Normal Hepatic Function Only:
•Matched to participants with mild or moderate hepatic function in sex, age, BMI, and smoking status
•In good health, as determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital sign measurements, and clinical laboratory evaluations
•Participants with Hepatic Impairment Only:
•Documented chronic stable liver disease
•Currently on a stable medication regimen, defined as not starting new drug(s) or changing drug dose(s) within 3 months of administration of study drug
•Anemia secondary to hepatic disease will be acceptable, if hemoglobin >/= 9 gram per decilitre (g/dL). Participants must have a platelet count </= 35 000 platelets

排除标准

•All Participants
•Significant history or clinical manifestation of any metabolic, allergic, dermatological, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder
•History of significant hypersensitivity, intolerance, or allergy to any drug compound, constituents or excipients of the study drug, food, or other substance
•History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered
•Ventricular dysfunction or history of risk factors for Torsades de Pointes
•Evidence of hepatorenal syndrome and estimated creatinine clearance range < 60 millilitre per minute (mL/min) or abnormal sodium and potassium levels
•Clinically significant physical examination abnormality
•History of diabetes mellitus
•Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's Wort
•Positive human immunodeficiency virus (HIV) test
•Participation in a clinical study involving administration of an investigational drug prior to dosing
•Smoke more than 10 cigarettes or use the equivalent tobacco- or nicotine-containing products per day
•Receipt of blood products within 2 months prior to study
•Donation of blood, plasma, or platelets prior to Screening
•Poor peripheral venous access
•Have previously completed or withdrawn from this study or any other study investigating risdiplam, and have previously received the investigational product
•Participants with Normal Hepatic Function Only:
•Confirmed supine blood pressure > 150 millimetre of mercury (mmHg) or < 90 mmHg
•Positive test for hepatitis B or C virus
•Clinically significant abnormal laboratory values
•Significant history or clinical manifestation of hepatic disorder
•History or presence of liver disease or liver injury
•Use or intend to use any prescription medications/products within 14 days prior to dosing
•. Use or intend to use slow-release medications/products considered to still be active within 14 days prior to dosing
•Use or intend to use any non-prescription medications/products within 7 days prior to dosing
•Participants with Hepatic Impairment Only:
•Confirmed supine blood pressure > 159 mmHg or < 90 mmHg
•Values outside the normal range for liver function tests that are not consistent with their hepatic condition
•Use of a new medication, or a change in dose, for the treatment, or worsening of, hepatic encephalopathy
•Use of prescription drugs within 14 days of study drug administration
•Recent history of, or the treatment of, esophageal bleeding
•Presence of a portosystemic shunt
•Recent history of paracentesis
•Current functioning organ transplant or are waiting for an organ transplant
•Evidence of severe ascites
•History or current symptoms of hepatic encephalopathy Grade 2 or above

研究组 & 干预措施

Part 1

Experimental

Participants with mild hepatic impairment and demographically matched healthy participants with normal hepatic function will be enrolled. Participants will receive a single oral dose of 5 mg risdiplam.

干预措施: Risdiplam (Drug)

Part 2

Experimental

Participants with moderate hepatic impairment and demographically matched healthy participants with normal hepatic function will be enrolled. Participants will receive a single oral dose of 5 mg risdiplam.

干预措施: Risdiplam (Drug)