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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

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:
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  • 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
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  • 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

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.

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 groupRoleWhat they receive
Part 1ExperimentalParticipants 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 2ExperimentalParticipants 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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)

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

  1. First posted19 Apr 2019
  2. Study start16 May 2019
  3. Primary completion2 Jan 2020
  4. Study completion2 Jan 2020

Resources

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
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).

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