- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03920865
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
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
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Florida
-
Miami, Florida, United States, 33014
- Clinical Pharmacology of Miami, Inc.
-
Orlando, Florida, United States, 32809
- Orlando Clinical Research Center
-
-
Texas
-
San Antonio, Texas, United States, 78215
- American Research Corporation Inc.
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
5 milligram (mg) oral dose administered in fasted state
|
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.
|
5 milligram (mg) oral dose administered in fasted state
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
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
|
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
|
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
|
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
|
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
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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.
|
Up to 31 Days
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Central Nervous System Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Neuromuscular Diseases
- Neurodegenerative Diseases
- Neuromuscular Manifestations
- Pathological Conditions, Anatomical
- Spinal Cord Diseases
- Atrophy
- Motor Neuron Disease
- Muscular Atrophy
- Muscular Atrophy, Spinal
- Physiological Effects of Drugs
- Peripheral Nervous System Agents
- Neuromuscular Agents
- Risdiplam
Other Study ID Numbers
- BP40995
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Muscular Atrophy, Spinal
-
Marco CapogrossoRoche-GenentechRecruitingSpinal Muscular Atrophy Type 3 | Spinal Muscular Atrophy Type 4United States
-
Institut de Myologie, FranceInstitut RocheCompletedType 2 Spinal Muscular Atrophy | Type 3 Spinal Muscular AtrophyBelgium, France, Germany
-
Marco CapogrossoRoche-GenentechNot yet recruitingSpinal Muscular Atrophy | Spinal Muscular Atrophy Type 3 | SMA | Spinal Muscular Atrophy Type II | Spinal Muscular Atrophy 4United States
-
Novartis Gene TherapiesActive, not recruitingSMA | Spinal Muscular Atrophy Type II | Spinal Muscular Atrophy Type I | Spinal Muscular Atrophy Type IIIUnited States, Belgium, France, Japan, United Kingdom, Italy, Taiwan, Australia, Canada
-
Hoffmann-La RocheRecruitingSpinal Muscular Atrophy (SMA)Belgium, United States, Croatia, Japan, Netherlands, Spain, Canada, Poland, United Kingdom, Italy, Portugal, Australia
-
Northwell HealthCompletedAdult Spinal Muscular AtrophyUnited States
-
Hugh McMillanFamilies of Spinal Muscular Atrophy; Gwendolyn Strong FoundationTerminatedSpinal Muscular Atrophy (SMA)Canada
-
Hoffmann-La RocheAssociation Française contre les Myopathies (AFM), ParisCompletedSpinal Muscular Atrophy Type II | Spinal Muscular Atrophy Type III Non AmbulantGermany, Italy, France, Belgium, Poland, Netherlands, United Kingdom
-
AveXis, Inc.United BioSource, LLCRecruitingSpinal Muscular Atrophy (SMA)Japan, United States, Korea, Republic of, Israel, Greece, Ireland, Portugal, Russian Federation, Taiwan
-
Istanbul Medipol University HospitalIstanbul UniversityRecruitingNeuromuscular Diseases | Spinal Muscular Atrophy Type 3Turkey
Clinical Trials on Risdiplam
-
Hoffmann-La RocheRecruiting
-
Hoffmann-La RocheCompleted
-
Hoffmann-La RocheRecruiting
-
Clinic for Special ChildrenGenentech, Inc.Active, not recruitingSpinal Muscular AtrophyUnited States
-
Hoffmann-La RocheNot yet recruiting
-
Hoffmann-La RocheActive, not recruitingMuscular Atrophy, SpinalUnited States, Belgium, Brazil, Russian Federation, Australia, Taiwan, Poland
-
Hoffmann-La RocheCompletedMuscular Atrophy, SpinalBelgium, United States, China, Spain, Japan, France, Brazil, Croatia, Italy, Russian Federation, Saudi Arabia, Serbia, Switzerland, Turkey, Ukraine, Poland
-
Genentech, Inc.Approved for marketingMuscular Atrophy, SpinalUnited States
-
Bakri ElsheikhGenentech, Inc.RecruitingSpinal Muscular AtrophyUnited States
-
Hoffmann-La RocheCompletedMuscular Atrophy, SpinalUnited States