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

NCT ID: NCT03920865

Last Updated: 2021-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-16
• Study Completion Date: 2020-01-02

Brief 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.

Conditions

Muscular Atrophy, Spinal

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1

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.

Group Type: EXPERIMENTAL

Risdiplam

Intervention Type: DRUG

5 milligram (mg) oral dose administered in fasted state

Part 2

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.

Group Type: EXPERIMENTAL

Risdiplam

Intervention Type: DRUG

5 milligram (mg) oral dose administered in fasted state

Interventions

Risdiplam

5 milligram (mg) oral dose administered in fasted state

Intervention Type: DRUG

Eligibility 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 </= 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Clinical Pharmacology of Miami, Inc.

Miami, Florida, United States

Orlando Clinical Research Center

Orlando, Florida, United States

American Research Corporation Inc.

San Antonio, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

BP40995

Identifier Type: -

Identifier Source: org_study_id