Muscular Atrophy, SpinalPhase 1NCT03920865

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 study testing Risdiplam in people with Muscular Atrophy, Spinal, run by Hoffmann-La Roche at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for: Muscular Atrophy, Spinal
What is being tested?: Risdiplam
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 26 participants
Where: 3 sitesUnited States
Study dates: 16 May 2019to 2 Jan 2020
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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:

Show all 12Show fewer

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

Who cannot join

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

Show all 36Show fewer

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 locations and contacts

3 sites in 1 country.

United States3 sites

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

Other trials in United States

About this study

Official title: An Open-Label, Single-Dose, Parallel-Group, Two-Part Study to Evaluate the Pharmacokinetics and Safety of Risdiplam in Subjects With Mild or Moderate Hepatic Impairment Compared to Subjects With Normal Hepatic Function

Conditions: Muscular Atrophy, Spinal
Being tested: Risdiplam
Medical subject headings: Muscular Atrophy, Spinal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT03920865
Study group	Role	What they receive
Part 1	Experimental	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. Receives: Drug: Risdiplam
Part 2	Experimental	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. Receives: Drug: Risdiplam

What is being measured

The primary outcome is the main question the study is designed to answer.

Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Risdiplam and Its Metabolite (M1)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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 (17)

Part 1: Time of the Maximum Observed Plasma Concentration (Tmax) of Risdiplam and M1
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: Up to 31 Days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 May 20192 Jan 2020

First posted19 Apr 2019
Study start16 May 2019
Primary completion2 Jan 2020
Study completion2 Jan 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Muscular Atrophy, SpinalStudies of the same condition, open and under way.
More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03920865
Sponsor's protocol ID: BP40995
Status last verified: Jan 2021
First submitted: 17 Apr 2019
Last updated: 21 Feb 2021
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: 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).

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Muscular Atrophy, Spinal trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label, Single-Dose, Parallel-Group, Two-Part Study to Evaluate the Pharmacokinetics and Safety of Risdiplam in Subjects With Mild or Moderate Hepatic Impairment Compared to Subjects With Normal Hepatic Function
ClinicalTrials.gov ID: NCT03920865
Acronym / sponsor ID: BP40995
Conditions: Muscular Atrophy, Spinal
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 26 participants (actual)
Lead sponsor: Hoffmann-La RocheIndustry (pharma, biotech, devices)
Study start: 16 May 2019 (actual)
Primary completion: 2 Jan 2020 (actual)
Study completion: 2 Jan 2020 (actual)
First posted: 19 Apr 2019 (actual)
Results: Posted 21 Feb 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Part 1	Experimental	Drug: RisdiplamParticipants 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.
Part 2	Experimental	Drug: RisdiplamParticipants 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.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

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
Matched to participants with mild or moderate hepatic function in sex, age, BMI, and smoking status

Key exclusion criteria (36 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Risdiplam5 milligram (mg) oral dose administered in fasted state	Drug	Part 1, Part 2

Primary outcome

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

17 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)
Time frame: Up to 31 Days

Results and safety

Results posted to the registry on 21 Feb 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Mild Hepatic Impairment	8	8
Moderate Hepatic Impairment	8	8
Normal Hepatic Function	10	10

Primary outcome: 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. Geometric mean (Geometric Coefficient of Variation). Unit: h*ng/mL

Measure	Risdiplam - Mild Hepatic Impairment n = 8	Risdiplam - Normal Hepatic Function n = 8	Risdiplam M1 Metabolite - Mild Hepatic Impairment n = 8	Risdiplam M1 Metabolite - Normal Hepatic Function n = 8
Value	792 (20.0)	987 (35.2)	222 (36.6)	263 (44.1)

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)

Population analysed: The PK population included all participants who received a dose of risdiplam and had evaluable PK data. A participant was excluded from the PK descriptive statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 times median time to maximum concentration or if they had any major protocol deviation(s) thought to impact PK analysis.

Primary outcome: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Risdiplam and M1

Measure	Risdiplam - Mild Hepatic Impairment n = 8	Risdiplam - Normal Hepatic Function n = 8	Risdiplam M1 Metabolite - Mild Hepatic Impairment n = 8	Risdiplam M1 Metabolite - Normal Hepatic Function n = 8
Value	773 (20.3)	961 (35.9)	197 (39.1)	245 (47.1)

Primary outcome: Part 1: Maximum Observed Plasma Concentration (Cmax) of Risdiplam and M1

Measure	Risdiplam - Mild Hepatic Impairment n = 8	Risdiplam - Normal Hepatic Function n = 8	Risdiplam M1 Metabolite - Mild Hepatic Impairment n = 8	Risdiplam M1 Metabolite - Normal Hepatic Function n = 8
Value	21.7 (23.5)	22.8 (46.9)	3.73 (30.4)	3.92 (36.3)

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)

Primary outcome: Part 2: AUCinf of Risdiplam and M1

Measure	Risdiplam - Moderate Hepatic Impairment n = 8	Risdiplam - Normal Hepatic Function n = 8	Risdiplam M1 Metabolite - Moderate Hepatic Impairment n = 8	Risdiplam M1 Metabolite - Normal Hepatic Function n = 8
Value	1040 (29.2)	971 (30.8)	261 (23.4)	275 (33.1)

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)

17 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 31 days post-dose. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Mild Hepatic Impairment	0 of 8 (0%)	5 of 8 (62.5%)	0 of 8
Moderate Hepatic Impairment	1 of 8 (12.5%)	0 of 8 (0%)	0 of 8
Normal Hepatic Function	0 of 10 (0%)	0 of 10 (0%)	0 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: 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).

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Trials study director

Hoffmann-La Roche

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Risdiplam in people with Muscular Atrophy, Spinal, run by Hoffmann-La Roche at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03920865.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2021.