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

Roche

Status and phase: Completed; Phase 1

Conditions: Muscular Atrophy, Spinal

Treatments: Drug: Risdiplam

Study type: Interventional

Funder types: Industry

Identifiers

NCT03920865

BP40995

Details and patient eligibility

About

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.

Enrollment: 26 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

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 </= 35 000 platelets

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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26 participants in 2 patient groups

Part 1

Experimental group

Description:

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.

Treatment:

Drug: Risdiplam

Part 2

Experimental group

Description:

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.

Treatment:

Drug: Risdiplam