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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/22/2021.

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

Clinicaltrials.gov identifier NCT03920865

Recruitment Status Completed

First Posted April 19, 2019

Last update posted January 10, 2020

Study Description

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.

  • Condition or Disease:Muscular Atrophy, Spinal
  • Intervention/Treatment: Drug: Risdiplam
  • Phase: Phase 1
Detailed Description

N/A

Study Design
  • Study Type: Interventional
  • Actual Enrollment: 26 participants
  • Allocation: Non-Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • 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
  • Actual Study Start Date: May 2019
  • Actual Primary Completion Date: January 2020
  • Actual Study Completion Date: January 2020
Arms and interventions
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.
Drug: 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.
Drug: Risdiplam
5 milligram (mg) oral dose administered in fasted state
Outcome Measures
  • Primary Outcome Measures: 1. Area Under the Plasma Concentration-Time Curve from Time 0 to Infinity (AUCinf) of Risdiplam [ Time Frame: Day 1 to Day 24 ]
  • 2. Area Under the Plasma Concentration-Time Curve from time 0 to the Last Measurable Concentration (AUClast) of Risdiplam [ Time Frame: Day 1 to Day 24 ]
    This measure will be used for pharmacokinetics (PK) comparison if AUCinf cannot be estimated with sufficient accuracy
  • 3. Maximum Observed Plasma Concentration (Cmax) of Risdiplam [ Time Frame: Day 1 to Day 24 ]
  • Secondary Outcome Measures: 1. Time of the Maximum Observed Plasma Concentration (Tmax) of Risdiplam [ Time Frame: Day 1 to Day 24 ]
  • 2. Apparent Plasma Terminal Elimination Half-Life (t1/2) of Risdiplam [ Time Frame: Day 1 to Day 24 ]
  • 3. Percentage of Area Under the Plasma Concentration-Time Curve Due to Extrapolation (%AUCextrap) of Risdiplam [ Time Frame: Day 1 to Day 24 ]
  • 4. Terminal Elimination Rate Constant (λz) of Risdiplam [ Time Frame: Day 1 to Day 24 ]
  • 5. Adjusted Coefficient for Determination of Exponential Fit (R2-adjusted) of Risdiplam [ Time Frame: Day 1 to Day 24 ]
  • 6. Apparent Total Clearance (CL/F) of Risdiplam [ Time Frame: Day 1 to Day 24 ]
  • 7. Fraction of Drug Unbound [ Time Frame: Day 1 to Day 24 ]
    Risdiplam and Metabolite (M1), as appropriate
  • 8. Molecular Weight-Adjusted Metabolite-To-Parent Ratio for AUCinf, Cmax, and AUClast [ Time Frame: Day 1 to Day 24 ]
  • 9. Percentage of Participants with Adverse Event (AE) or Serious Adverse Event (SAE) [ Time Frame: From Screening to Day 28 ]
Eligibility Criteria
  • Ages Eligible for Study: 18 to 70 Years (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: Yes
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 150 millimetre of mercury (mmHg) or 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

Contacts and Locations
Contacts
Locations

United States, Florida
Clinical Pharmacology of Miami, Inc.
Miami

United States, Florida
Orlando Clinical Research Center
Orlando

United States, Texas
American Research Corporation Inc.
San Antonio

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials Hoffmann-La Roche

More Information
  • Responsible Party: Hoffmann-La Roche
  • ClinicalTrials.gov Identifier: NCT03920865 History of Changes
  • Other Study ID Numbers: BP40995
  • First Posted: April 19, 2019 Key Record Dates
  • Last Update Posted: January 10, 2020
  • Last Verified: January 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: No
  • Plan Description: 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).
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Additional relevant MeSH terms: Muscular Atrophy
    Muscular Atrophy, Spinal
    Atrophy