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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05098054
• Other study ID #: TAK-935-1010
• Secondary ID: 2021-006373-29
• Status: Completed
• Phase: Phase 1
• Start date: October 29, 2021
• Est. completion date: June 7, 2022

Study information

• Verified date: May 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: June 7, 2022
• Est. primary completion date: May 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers
• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• Soticlestat
Soticlestat tablets.

Locations

Country	Name	City	State
Hungary	CRU Hungary Unit Pest Country Flor Ferenc Hospital	Kistarcsa
United States	Velocity	Edgewater	Florida
United States	Clinical Pharmacology of Miami	Miami	Florida
United States	Orlando Clinical Research Center	Orlando	Florida
United States	GCP	Saint Petersburg	Florida
United States	Texas Liver Institute	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

United States,  Hungary, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax: Maximum Observed Plasma Concentration for Soticlestat		Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose
Primary	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
Primary	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	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)

External Links

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