A Study of Soticlestat in Adults With Liver Failure Compared to Those With Normal Liver Function

Sponsor
Takeda (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05098054
Collaborator
(none)
40
Enrollment
3
Locations
3
Arms
11.7
Anticipated Duration (Months)
13.3
Patients Per Site
1.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main aim is to check the effect of a single dose of soticlestat in adults with moderate or severe liver failure compared to healthy adults with normal liver function.

Participants will check into the study clinic for 8 days. During the stay, one oral dose of soticlestat will be given and the participant will be monitored. The clinic staff will follow up with the participant about a week after discharge from the clinic.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1

Detailed Description

The drug being tested in this study is called soticlestat (TAK-935). The study will assess the safety and tolerability of single oral dose of soticlestat in participants with moderate or severe Hepatic Impairment (HI) compared to healthy participants matched by age (mean ±10 years), sex (±2 per sex), and body mass index (BMI, mean ±10 percent [%]) with normal hepatic function.

The study will enroll approximately 40 participants. Participants will be assigned to following study arms:

  • Arm 1, Moderate HI: Soticlestat 300 milligram (mg) (Child-Pugh B)

  • Arm 2, Severe HI: Soticlestat 300 mg or lower dose (Child-Pugh C)

  • Arm 3, Normal hepatic function: Soticlestat 300 mg or lower dose

All participants will receive single oral dose of study drug. The data will be collected and stored in electronic case report form (eCRF).

This multi-center trial will be conducted in the United States. The overall duration of the study is approximately 42 days. Participants will be followed up for 14 days after the last dose of study drug for a follow-up assessment.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
40 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
Phase 1 Pharmacokinetics and Safety Study of Oral Soticlestat in Participants With Moderate or Severe Hepatic Impairment and Normal Hepatic Function
Actual Study Start Date :
Oct 28, 2021
Anticipated Primary Completion Date :
Jun 10, 2022
Anticipated Study Completion Date :
Oct 19, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: Arm 1, Moderate HI: Soticlestat 300 mg

Soticlestat 300 mg, tablets, orally, once on Day 1 to participant with moderate HI.

Drug: Soticlestat
Soticlestat tablets.
Other Names:
  • TAK-935
  • Experimental: Arm 2, Severe HI: Soticlestat 300 mg or lower dose

    Soticlestat 300 mg or lower, tablets, orally, once on Day 1 to participant with severe HI.

    Drug: Soticlestat
    Soticlestat tablets.
    Other Names:
  • TAK-935
  • Experimental: Arm 3, Normal hepatic function: Soticlestat 300 mg or lower dose

    Soticlestat 300 mg or lower, tablets, orally, once on Day 1 to healthy participants.

    Drug: Soticlestat
    Soticlestat tablets.
    Other Names:
  • TAK-935
  • Outcome Measures

    Primary Outcome Measures

    1. Cmax: Maximum Observed Plasma Concentration for Soticlestat [Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose]

    2. AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Soticlestat [Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose]

    3. AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Soticlestat [Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose]

    Secondary Outcome Measures

    1. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) [Baseline up to Day 17]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes

    Inclusion Criteria A. For Participants with Hepatic Impairment

    1. Has a BMI greater than or equal to (>=) 18.0 and less than or equal to (<=) 40.0 kilogram per square meter (kg/m2), at screening. At least 50% of the participants will be required to be of BMI >=18.0 and <=35.0 kg/m2, at screening.
    • Supine blood pressure (BP) is >=80/40 millimeter of mercury (mmHg) (asymptomatic) and <=150/95 mmHg at screening;

    • Supine pulse rate (PR) is >=40 beats per minute (bpm) and <=99 bpm, at screening;

    • QT interval corrected for heart rate using Fridericia's formula (QTcF) is <=500 millisecond (msec) and ECG findings considered normal or not clinically significant by the Investigator or designee, at screening.

    1. Must have had chronic HI for at least 3 months before screening, and the HI must be stable, that is, no significant changes in hepatic function in the 30 days preceding screening (or since the last visit if within 6 months before screening) and treatment with stable doses of medication. Has a score on the Child-Pugh Class at screening as follows:
    • (Arm 1) Moderate HI, Child-Pugh Class B: >=7 and <=9

    • (Arm 2) Severe HI, Child-Pugh Class C: >=10 and <=15

    1. Should not have renal dysfunction as demonstrated by a relatively adequate renal function (creatinine clearance >=50 milliliter per minute [mL/min]/1.73 meter square [m^2]), at screening.
    1. For Healthy Participants
    1. Has a BMI >=18.0 and <=40.0 kg/m2, at screening. At least 50% of the participants will be required to be of BMI >=18.0 and <=35.0 kg/m2, at screening. Healthy participants will be matched to hepatic impaired participants in this study by age (mean ±10 years), sex (±2 per sex), and BMI, mean ±10%.
    • Supine BP is >=90/40 mmHg and <=150/95 mmHg, at screening;

    • Supine PR is >=40 bpm and <=99 bpm, at screening;

    • QTcF is <=450 msec (males) or <=470 msec (females) and ECG findings considered normal or not clinically significant by the Investigator or designee, at screening;

    • Liver function tests including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin <= the upper limit of normal (ULN) at screening and check-in.

    1. Should not have renal dysfunction as demonstrated by a relatively adequate renal function (creatinine clearance >=60 mL/min/1.73m^2), at screening.
    1. For Participants with Hepatic Impairment and Healthy Participants
    1. Continuous non-smoker or moderate smoker (<=10 cigarettes/day or the equivalent) before screening. Participant must agree to consume no more than 5 cigarettes or equivalent/day from the 7 days prior check-in and until discharge from the Clinical Research Unit (CRU).

    Exclusion Criteria A. For Participants with Hepatic Impairment

    1. Has history or presence of clinically significant medical or psychiatric condition or disease (aside from HI) or presence of psychotic disorders such as psychosis, delusions, or schizophrenia in the opinion of the Investigator or designee.

    2. Has a history of liver or other solid organ transplant.

    3. Positive result at screening for human immunodeficiency virus (HIV). Hepatitis B surface antigen (HBsAg) positive participants are allowed to be enrolled if Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is below 1000 copies per milliliter (/mL) in the plasma. Participants with moderate HI who are positive for Hepatitis C virus antibodies (HCVAb) can be enrolled but must not have detectable Hepatitis C virus (HCV) ribonucleic acid (RNA) in the plasma. Participants with severe HI who are positive for HCVAb can be enrolled regardless of viral load.

    1. For Healthy Participants
    1. Has history or presence of clinically significant medical or psychiatric condition or disease or presence of psychotic disorders such as psychosis, delusions, or schizophrenia in the opinion of the Investigator or designee.

    2. Positive results at screening for HIV, HBsAg, or HCV.

    1. For Participants with Hepatic Impairment and Healthy Participants
    1. Has been on a diet incompatible with the on-study diet, in the opinion of the Investigator or designee, within the 30 days prior to dosing.

    2. Any positive responses on the Columbia-Suicide Severity Rating Scale (C-SSRS) or has a risk of suicide according to the Investigator's judgment based on the assessment of the C-SSRS at screening or check-in or has made a suicide attempt in the previous 12 months prior to dosing.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Clinical Pharmacology of MiamiHialeahFloridaUnited States33014
    2Orlando Clinical Research CenterOrlandoFloridaUnited States32809-3017
    3Texas Liver InstituteSan AntonioTexasUnited States78215

    Sponsors and Collaborators

    • Takeda

    Investigators

    • Study Director: Study Director, Takeda

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT05098054
    Other Study ID Numbers:
    • TAK-935-1010
    • 2021-006373-29
    First Posted:
    Oct 28, 2021
    Last Update Posted:
    Dec 1, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Takeda
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Dec 1, 2021