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
Condition: Muscular Atrophy, Spinal
MeSH terms: Muscular Atrophy; Muscular Atrophy, Spinal
Intervention: Risdiplam
Intervention description: 5 milligram (mg) oral dose administered in fasted state
Intervention MeSH terms: Risdiplam
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

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