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

NCT03920865 | Completed Phase 1 Results FDA Drug

• 1 other identifier: BP40995
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

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

Outcome Measures

Primary Outcomes (6)

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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

Study Arms (2)

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.

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.

Drug: Risdiplam

Interventions

Risdiplam DRUG

5 milligram (mg) oral dose administered in fasted state

Part 1; Part 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (3)

Clinical Pharmacology of Miami, Inc.

Miami, Florida, 33014, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

American Research Corporation Inc.

San Antonio, Texas, 78215, United States

Location

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Interventions

Risdiplam

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2019
• First Posted: April 19, 2019
• Study Start: May 16, 2019
• Primary Completion: January 2, 2020
• Study Completion: January 2, 2020
• Last Updated: February 21, 2021
• Results First Posted: February 21, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)