A Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics and Safety and Tolerability of a Single Oral Dose of Risdiplam Compared to Matched Healthy Participants With Normal Hepatic Function

• Status: Completed
• Trial end date: 2020-01-02
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Hoffmann-La Roche
• Treatments: Risdiplam

Criteria

Inclusion Criteria:

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 Exclusion Criteria:

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