Clinical trial NCT05098054: A Study of Soticlestat in Adults With Liver Failure Compared to Those With Normal Liver Function
Official title: Phase 1 Pharmacokinetics and Safety Study of Oral Soticlestat in Participants With Moderate or Mild Hepatic Impairment and Normal Hepatic Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Healthy Volunteers
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2021-10-28
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for Soticlestat
timeFrame: Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose
measure: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity for Soticlestat
timeFrame: Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose
measure: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Soticlestat
timeFrame: Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose
Secondary outcomes:
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
timeFrame: From Day 1 up to 16 days after the last dose of study drug (up to Day 17)
Other outcomes:
Locations:
city: Edgewater
country: United States
facility: Velocity
state: Florida
city: Miami
country: United States
facility: Clinical Pharmacology of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Saint Petersburg
country: United States
facility: GCP
state: Florida
city: San Antonio
country: United States
facility: Texas Liver Institute
state: Texas
city: Kistarcsa
country: Hungary
facility: CRU Hungary Unit Pest Country Flor Ferenc Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: