CompletedNCT03920865Updated Feb 21, 2021Results posted

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

A Phase 1 interventional study of Risdiplam in Muscular Atrophy, Spinal, sponsored by Hoffmann-La Roche. Completed at 3 sites in United States. Open to participants aged 18 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-02-21.

Sponsored by Hoffmann-La Roche · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 26
Allocation: Non-randomized
Ages: 18 Years to 70 Years
Sex: All

Study 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 studied

Muscular Atrophy, Spinal

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In context

Muscular Atrophy

494 studies on the registry are indexed under Muscular Atrophy; 94 are open to participants now.

This study's enrollment of 26 is below the median of 33 across 335 interventional studies indexed under Muscular Atrophy.

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Lead sponsor

Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.

Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 70 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

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

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

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 26 participants (actual)

Study arms

Experimental
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.
Drug: Risdiplam
Experimental
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.
Drug: Risdiplam

Interventions

DrugRisdiplam
5 milligram (mg) oral dose administered in fasted state

What researchers measure

Primary outcomes

Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Risdiplam and Its Metabolite (M1)
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Risdiplam and M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 1: Maximum Observed Plasma Concentration (Cmax) of Risdiplam and M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 2: AUCinf of Risdiplam and M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 2: AUClast of Risdiplam and M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 2: Cmax of Risdiplam and M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose

Secondary outcomes

Part 1: Time of the Maximum Observed Plasma Concentration (Tmax) of Risdiplam and M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 1: Apparent Plasma Terminal Elimination Half-Life (t1/2) of Risdiplam and M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 1: Percentage of Area Under the Plasma Concentration-Time Curve Due to Extrapolation (%AUCextrap) of Risdiplam and M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 1: Terminal Elimination Rate Constant (λz=Lambda-Z) of Risdiplam and M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 1: Apparent Total Clearance (CL/F) of Risdiplam
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 1: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for AUCinf of Risdiplam M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 1: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for Cmax of Risdiplam M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 1: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for AUClast of Risdiplam M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 2: Tmax of Risdiplam and M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 2: t1/2 of Risdiplam and M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 2: %AUCextrap of Risdiplam and M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 2: λz of Risdiplam and M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 2: CL/F of Risdiplam and M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 2: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for AUCinf of Risdiplam M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 2: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for Cmax of Risdiplam M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 2: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for AUClast of Risdiplam M1
Time frame: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Part 1 and Part 2: Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time frame: Up to 31 Days

Results

Posted Feb 21, 2021

Participant flow

Participant flow — Overall Study
Milestone	Mild Hepatic Impairment	Moderate Hepatic Impairment	Normal Hepatic Function
Started	8	8	10
Completed	8	8	10
Not completed	0	0	0

Outcome measures

PrimaryPart 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Risdiplam and Its Metabolite (M1)

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · h*ng/mL

Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Risdiplam and Its Metabolite (M1)
h*ng/mL	Risdiplam - Mild Hepatic Impairment	Risdiplam - Normal Hepatic Function	Risdiplam M1 Metabolite - Mild Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Risdiplam and Its Metabolite (M1)	792 ± 20.0	987 ± 35.2	222 ± 36.6	263 ± 44.1

Statistical analysis

Risdiplam - Mild Hepatic Impairment vs Risdiplam - Normal Hepatic Function · Ratio of geometric least squares means: 0.802 · 90% CI 0.627 to 1.03
Risdiplam M1 Metabolite - Mild Hepatic Impairment vs Risdiplam M1 Metabolite - Normal Hepatic Function · Ratio of geometric least squares means: 0.842 · 90% CI 0.588 to 1.21

PrimaryArea Under the Plasma Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Risdiplam and M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · h*ng/mL

Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Risdiplam and M1
h*ng/mL	Risdiplam - Mild Hepatic Impairment	Risdiplam - Normal Hepatic Function	Risdiplam M1 Metabolite - Mild Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Risdiplam and M1	773 ± 20.3	961 ± 35.9	197 ± 39.1	245 ± 47.1

PrimaryPart 1: Maximum Observed Plasma Concentration (Cmax) of Risdiplam and M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · ng/mL

Part 1: Maximum Observed Plasma Concentration (Cmax) of Risdiplam and M1
ng/mL	Risdiplam - Mild Hepatic Impairment	Risdiplam - Normal Hepatic Function	Risdiplam M1 Metabolite - Mild Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 1: Maximum Observed Plasma Concentration (Cmax) of Risdiplam and M1	21.7 ± 23.5	22.8 ± 46.9	3.73 ± 30.4	3.92 ± 36.3

Statistical analysis

Risdiplam - Mild Hepatic Impairment vs Risdiplam - Normal Hepatic Function · Ratio of geometric least squares means: 0.950 · 90% CI 0.695 to 1.30
Risdiplam M1 Metabolite - Mild Hepatic Impairment vs Risdiplam M1 Metabolite - Normal Hepatic Function · Ratio of geometric least squares means: 0.953 · 90% CI 0.715 to 1.27

PrimaryPart 2: AUCinf of Risdiplam and M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · h*ng/mL

Part 2: AUCinf of Risdiplam and M1
h*ng/mL	Risdiplam - Moderate Hepatic Impairment	Risdiplam - Normal Hepatic Function	Risdiplam M1 Metabolite - Moderate Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 2: AUCinf of Risdiplam and M1	1040 ± 29.2	971 ± 30.8	261 ± 23.4	275 ± 33.1

Statistical analysis

Risdiplam - Moderate Hepatic Impairment vs Risdiplam - Normal Hepatic Function · Ratio of geometric least squares means: 1.08 · 90% CI 0.830 to 1.39
Risdiplam M1 Metabolite - Moderate Hepatic Impairment vs Risdiplam M1 Metabolite - Normal Hepatic Function · Ratio of geometric least squares means: 0.947 · 90% CI 0.740 to 1.21

PrimaryPart 2: AUClast of Risdiplam and M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · h*ng/mL

Part 2: AUClast of Risdiplam and M1
h*ng/mL	Risdiplam - Moderate Hepatic Impairment	Risdiplam - Normal Hepatic Function	Risdiplam M1 Metabolite - Moderate Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 2: AUClast of Risdiplam and M1	1020 ± 29.7	947 ± 31.2	243 ± 24.9	259 ± 33.9

PrimaryPart 2: Cmax of Risdiplam and M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · ng/mL

Part 2: Cmax of Risdiplam and M1
ng/mL	Risdiplam - Moderate Hepatic Impairment	Risdiplam - Normal Hepatic Function	Risdiplam M1 Metabolite - Moderate Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 2: Cmax of Risdiplam and M1	29.9 ± 18.8	25.0 ± 30.2	4.10 ± 24.0	4.13 ± 22.5

Statistical analysis

Risdiplam - Moderate Hepatic Impairment vs Risdiplam - Normal Hepatic Function · Ratio of geometric least squares means: 1.20 · 90% CI 0.962 to 1.49
Risdiplam M1 Metabolite - Moderate Hepatic Impairment vs Risdiplam M1 Metabolite - Normal Hepatic Function · Ratio of geometric least squares means: 0.991 · 90% CI 0.810 to 1.21

SecondaryPart 1: Time of the Maximum Observed Plasma Concentration (Tmax) of Risdiplam and M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Median · hours (h)

Part 1: Time of the Maximum Observed Plasma Concentration (Tmax) of Risdiplam and M1
hours (h)	Risdiplam - Mild Hepatic Impairment	Risdiplam - Normal Hepatic Function	Risdiplam M1 Metabolite - Mild Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 1: Time of the Maximum Observed Plasma Concentration (Tmax) of Risdiplam and M1	4.00 (2.00 to 4.00)	4.00 (2.00 to 4.00)	10.00 (4.00 to 24.00)	10.00 (4.00 to 24.00)

SecondaryPart 1: Apparent Plasma Terminal Elimination Half-Life (t1/2) of Risdiplam and M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · h

Part 1: Apparent Plasma Terminal Elimination Half-Life (t1/2) of Risdiplam and M1
h	Risdiplam - Mild Hepatic Impairment	Risdiplam - Normal Hepatic Function	Risdiplam M1 Metabolite - Mild Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 1: Apparent Plasma Terminal Elimination Half-Life (t1/2) of Risdiplam and M1	41.3 ± 29.1	55.0 ± 16.2	32.9 ± 19.1	38.2 ± 18.7

SecondaryPart 1: Percentage of Area Under the Plasma Concentration-Time Curve Due to Extrapolation (%AUCextrap) of Risdiplam and M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · Percentage (%) of AUCextrap

Part 1: Percentage of Area Under the Plasma Concentration-Time Curve Due to Extrapolation (%AUCextrap) of Risdiplam and M1
Percentage (%) of AUCextrap	Risdiplam - Mild Hepatic Impairment	Risdiplam - Normal Hepatic Function	Risdiplam M1 Metabolite - Mild Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 1: Percentage of Area Under the Plasma Concentration-Time Curve Due to Extrapolation (%AUCextrap) of Risdiplam and M1	2.34 ± 29.1	2.53 ± 32.8	7.49 ± 54.0	6.28 ± 38.7

SecondaryPart 1: Terminal Elimination Rate Constant (λz=Lambda-Z) of Risdiplam and M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · h-1

Part 1: Terminal Elimination Rate Constant (λz=Lambda-Z) of Risdiplam and M1
h-1	Risdiplam - Mild Hepatic Impairment	Risdiplam - Normal Hepatic Function	Risdiplam M1 Metabolite - Mild Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 1: Terminal Elimination Rate Constant (λz=Lambda-Z) of Risdiplam and M1	0.0168 ± 29.1	0.0126 ± 16.2	0.0211 ± 19.1	0.0182 ± 18.7

SecondaryPart 1: Apparent Total Clearance (CL/F) of Risdiplam

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · L/h

Part 1: Apparent Total Clearance (CL/F) of Risdiplam
L/h	Risdiplam - Mild Hepatic Impairment	Risdiplam - Normal Hepatic Function
Part 1: Apparent Total Clearance (CL/F) of Risdiplam	6.31 ± 20.0	5.07 ± 35.2

SecondaryPart 1: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for AUCinf of Risdiplam M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · Ratio

Part 1: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for AUCinf of Risdiplam M1
Ratio	Risdiplam M1 Metabolite - Mild Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 1: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for AUCinf of Risdiplam M1	0.258 ± 22.7	0.255 ± 12.0

SecondaryPart 1: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for Cmax of Risdiplam M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · Ratio

Part 1: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for Cmax of Risdiplam M1
Ratio	Risdiplam M1 Metabolite - Mild Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 1: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for Cmax of Risdiplam M1	0.165 ± 29.4	0.164 ± 15.5

SecondaryPart 1: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for AUClast of Risdiplam M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · Ratio

Part 1: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for AUClast of Risdiplam M1
Ratio	Risdiplam M1 Metabolite - Mild Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 1: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for AUClast of Risdiplam M1	0.244 ± 24.8	0.245 ± 13.8

SecondaryPart 2: Tmax of Risdiplam and M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Median · hours (h)

Part 2: Tmax of Risdiplam and M1
hours (h)	Risdiplam - Moderate Hepatic Impairment	Risdiplam - Normal Hepatic Function	Risdiplam M1 Metabolite - Moderate Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 2: Tmax of Risdiplam and M1	2.00 (1.00 to 4.00)	4.00 (1.00 to 4.00)	24.00 (10.00 to 24.03)	11.00 (4.00 to 24.00)

SecondaryPart 2: t1/2 of Risdiplam and M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · h

Part 2: t1/2 of Risdiplam and M1
h	Risdiplam - Moderate Hepatic Impairment	Risdiplam - Normal Hepatic Function	Risdiplam M1 Metabolite - Moderate Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 2: t1/2 of Risdiplam and M1	45.6 ± 28.0	49.9 ± 28.1	34.5 ± 24.3	35.0 ± 21.6

SecondaryPart 2: %AUCextrap of Risdiplam and M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · Percentage (%) of AUCextrap

Part 2: %AUCextrap of Risdiplam and M1
Percentage (%) of AUCextrap	Risdiplam - Moderate Hepatic Impairment	Risdiplam - Normal Hepatic Function	Risdiplam M1 Metabolite - Moderate Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 2: %AUCextrap of Risdiplam and M1	1.90 ± 33.5	2.41 ± 30.5	6.58 ± 28.8	5.68 ± 23.6

SecondaryPart 2: λz of Risdiplam and M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · h-1

Part 2: λz of Risdiplam and M1
h-1	Risdiplam - Moderate Hepatic Impairment	Risdiplam - Normal Hepatic Function	Risdiplam M1 Metabolite - Moderate Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 2: λz of Risdiplam and M1	0.0152 ± 28.0	0.0139 ± 28.1	0.0201 ± 24.3	0.0198 ± 21.6

SecondaryPart 2: CL/F of Risdiplam and M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · L/h

Part 2: CL/F of Risdiplam and M1
L/h	Risdiplam - Moderate Hepatic Impairment	Risdiplam - Normal Hepatic Function
Part 2: CL/F of Risdiplam and M1	4.79 ± 29.2	5.15 ± 30.8

SecondaryPart 2: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for AUCinf of Risdiplam M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · Ratio

Part 2: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for AUCinf of Risdiplam M1
Ratio	Risdiplam M1 Metabolite - Moderate Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 2: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for AUCinf of Risdiplam M1	0.239 ± 16.8	0.271 ± 10.3

SecondaryPart 2: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for Cmax of Risdiplam M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · Ratio

Part 2: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for Cmax of Risdiplam M1
Ratio	Risdiplam M1 Metabolite - Moderate Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 2: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for Cmax of Risdiplam M1	0.131 ± 16.3	0.158 ± 15.0

SecondaryPart 2: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for AUClast of Risdiplam M1

Time frame:: Predose, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 312, 336, 360, 408, 456, 504, and 552 hours Postdose
Reported as:: Geometric mean · Ratio

Part 2: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for AUClast of Risdiplam M1
Ratio	Risdiplam M1 Metabolite - Moderate Hepatic Impairment	Risdiplam M1 Metabolite - Normal Hepatic Function
Part 2: Molecular Weight-Adjusted Metabolite-to-Parent Ratio for AUClast of Risdiplam M1	0.227 ± 16.8	0.262 ± 10.0

SecondaryPart 1 and Part 2: Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Time frame:: Up to 31 Days
Reported as:: Number · Percentage of Participants

Part 1 and Part 2: Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Percentage of Participants	Part 1	Part 2	Normal Hepatic Function Participants
With at least one AE	62.5	12.5	0.0
With at least one SAE	0.0	12.5	0.0

Adverse events

Collected over Up to 31 days post-dose. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Mild Hepatic Impairment	0/8 (0%)	0/8 (0%)	5/8 (62.5%)
Moderate Hepatic Impairment	0/8 (0%)	1/8 (12.5%)	0/8 (0%)
Normal Hepatic Function	0/10 (0%)	0/10 (0%)	0/10 (0%)

Most frequent serious events

Most frequent serious events
Event	Mild Hepatic Impairment	Moderate Hepatic Impairment	Normal Hepatic Function
Upper gastrointestinal haemorrhageGastrointestinal disorders	0/8	1/8	0/10

Most frequent other events

Most frequent other events
Event	Mild Hepatic Impairment	Moderate Hepatic Impairment	Normal Hepatic Function
VomitingGastrointestinal disorders	2/8	0/8	0/10
Ear painEar and labyrinth disorders	1/8	0/8	0/10
DiarrhoeaGastrointestinal disorders	1/8	0/8	0/10
DyspepsiaGastrointestinal disorders	1/8	0/8	0/10
Chest discomfortGeneral disorders	1/8	0/8	0/10
PruritusSkin and subcutaneous tissue disorders	1/8	0/8	0/10

Baseline characteristics

Age, Continuous
Age, Continuous(Years)	Mild Hepatic Impairment	Moderate Hepatic Impairment	Normal Hepatic Function	Total
Mean	61.5 ± 4.0	56.6 ± 6.3	57.3 ± 6.8	58.4 ± 6.1

Sex: Female, Male
Sex: Female, Male(Participants)	Mild Hepatic Impairment	Moderate Hepatic Impairment	Normal Hepatic Function	Total
Female	4	4	5	13
Male	4	4	5	13

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Mild Hepatic Impairment	Moderate Hepatic Impairment	Normal Hepatic Function	Total
Hispanic or Latino	3	4	7	14
Not Hispanic or Latino	5	4	3	12

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Mild Hepatic Impairment	Moderate Hepatic Impairment	Normal Hepatic Function	Total
Black or African American	2	1	0	3
White	6	7	10	23

Study locations

3 sites

Clinical Pharmacology of Miami, Inc.
Miami, Florida 33014, United States
Orlando Clinical Research Center
Orlando, Florida 32809, United States
American Research Corporation Inc.
San Antonio, Texas 78215, United States

References and documents

Study documents

Study protocol · Jan 8, 2019
Statistical analysis plan · Oct 22, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Feb 21, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03920865
Lead sponsor: Hoffmann-La Roche
Responsible party: Sponsor
First posted: Apr 19, 2019
Start date: May 16, 2019
Primary completion: Jan 2, 2020
Completion: Jan 2, 2020
Results posted: Feb 21, 2021
Last update: Feb 21, 2021

Study contacts

Clinical Trials

study director · Hoffmann-La Roche

Oversight

FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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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

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