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

Phase 1 Pharmacokinetics and Safety Study of Oral Soticlestat in Participants With Moderate or Mild Hepatic Impairment and Normal Hepatic Function

The main aim is to check the effect of a single dose of soticlestat in adults with moderate or mild 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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Hepatic Impairment
• Intervention / Treatment: Drug: Soticlestat

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 mild 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 Class B)
• Arm 2, Mild HI: Soticlestat 300 mg (Child-Pugh Class A)
• Arm 3, Normal hepatic function: Soticlestat 300 mg

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 and Hungary. 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 Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Hungary
  • Kistarcsa, Hungary, 2143
    • CRU Hungary Unit Pest Country Flor Ferenc Hospital
• United States
  • Florida
    • Edgewater, Florida, United States, 32132
      • Velocity
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami
    • Orlando, Florida, United States, 32809-3017
      • Orlando Clinical Research Center
    • Saint Petersburg, Florida, United States, 33705
      • GCP
  • Texas
    • San Antonio, Texas, United States, 78215
      • Texas Liver Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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/m^2), at screening. At least 50% of the participants will be required to be of BMI >=18.0 and <=35.0 kg/m^2, 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.

2. 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) Mild HI, Child-Pugh Class A: >=5 and <=6
3. Should not have renal dysfunction as demonstrated by a relatively adequate renal function (creatinine clearance >=50 milliliter per minute [mL/min]), at screening.

B. For Healthy Participants

1. Has a BMI >=18.0 and <=40.0 kg/m^2, at screening. At least 50% of the participants will be required to be of BMI >=18.0 and <=35.0 kg/m^2, 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.
2. Should not have renal dysfunction as demonstrated by a relatively adequate renal function (creatinine clearance >=60 mL/min), at screening.

C. 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 or mild 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.

B. 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.

C. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / 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, Mild HI: Soticlestat 300 mg; Soticlestat 300 mg, tablets, orally, once on Day 1 to participant with mild HI.	Drug: Soticlestat; Soticlestat tablets.; Other Names: TAK-935
Experimental: Arm 3, Normal hepatic function: Soticlestat 300 mg; Soticlestat 300 mg, tablets, orally, once on Day 1 to healthy participants.	Drug: Soticlestat; Soticlestat tablets.; Other Names: TAK-935

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax: Maximum Observed Plasma Concentration for Soticlestat	Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose
AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity for Soticlestat	Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to 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

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE was defined as an AE that started or worsened at the time of or after dosing of study drug.	From Day 1 up to 16 days after the last dose of study drug (up to Day 17)

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2021
• Primary Completion (Actual): May 31, 2022
• Study Completion (Actual): June 7, 2022

Study Registration Dates

• First Submitted: October 20, 2021
• First Submitted That Met QC Criteria: October 20, 2021
• First Posted (Actual): October 28, 2021

Study Record Updates

• Last Update Posted (Estimated): February 2, 2024
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: TAK-935-1010; 2021-006373-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• 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