A Study of Soticlestat in Healthy Adults To Evaluate the Effect on QTc Interval

Takeda

Overview

The main aim is to see if soticlestat has any effect in the heart rate. Participants will receive 4 doses of soticlestat in tablets and will complete some assessment which include to record activity of the heart and collection of blood samples. Then, the clinic will contact the participants 14 days after their final dose of soticlestat to check if they have any health problems.

The drug being tested in this study is called soticlestat. Soticlestat is being tested in healthy participants for the purpose of this study. This study will assess the effect of single-dose of soticlestat on the heart rate (QTc prolongation). The study will enroll approximately 60 participants. Participants will be randomly assigned (by chance, like flipping a coin) to 1 of the 4 treatments sequences. * Sequence 1: (Regimen A+ Regimen B + Regimen C + Regimen D) * Sequence 2: (Regimen B+ Regimen D + Regimen A + Regimen C) * Sequence 3: (Regimen C+ Regimen A + Regimen D + Regimen B) * Sequence 4: (Regimen D+ Regimen C + Regimen B + Regimen A) All participants will receive all 4 treatment regimens. Treatment order will remain undisclosed to the participants and study doctor (unless there is an urgent medical need). This is a single-center trial. Participants will be followed up for up to 14 days after the last dose of study drug for a follow-up assessment. The overall time to participate in this study is approximately 63 days including screening period and follow-up period.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

QUADRUPLE

Conditions

Healthy Volunteers

Interventions

SoticlestatDRUG

Soticlestat tablet.

PlaceboDRUG

Soticlestat placebo-matching tablet.

MoxifloxacinDRUG

Moxifloxacin over-encapsulated tablet.

Placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Male participants agree to comply with any applicable contraceptive requirements of the protocol. 2. Body mass index (BMI) greater than or equal to (\>=)18.0 and \<=32.0 kilogram per square meter (kg/m\^2) at screening. 3. Continuous non-smoker who has not used nicotine-containing products for at least 90 days prior to the first dosing, based on participant self-reporting. 4. No clinically significant history or presence of ECG findings as judged by the Investigator or designee, including each criterion as listed below: * Normal sinus rhythm (HR between 45 bpm and 100 bpm inclusive) at screening and check-in; * QTcF is \<=450 ms (males) or \<=470 ms (females) at screening and check-in; * QRS interval \<=110 ms; if \>110 ms, result will be confirmed by a manual over read at screening and check-in; * PR interval \<=220 ms at screening and check-in. Exclusion Criteria: 1. Mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study. 2. History or presence of any of the following, deemed clinically significant by the Investigator or designee: * epilepsy, seizure, or convulsion, tremor or related symptoms; * risk factors for Torsade de Pointes (TdP) (example, heart failure, unexplained syncope, cardiomyopathy, or family history of Long QT Syndrome); * family history of sudden death; * sick sinus syndrome, second or third degree atrioventricular block, myocardial infarction, pulmonary congestion, symptomatic or significant cardiac arrhythmia, prolonged QTcF interval, or conduction abnormalities; * ischemic heart disease, poorly controlled hypertension, or other cardiovascular disorder; * T wave flattening or other abnormalities which in the opinion of the investigator or designee may interfere with the analysis of QT intervals; * clinically significant hyper- or hypokalemia. 3. Any positive responses on the Columbia-Suicide Severity Rating Scale (C-SSRS) that in the clinical judgement of the Investigator has a risk of suicide or has made a suicide attempt in the previous 12 months prior to the first dosing. 4. Positive urine drug or alcohol results at screening or at check-in. 5. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or antibody test for hepatitis C virus (HCV). 6. Unable to refrain from or anticipates the use of: * Any vaccines, drugs, including prescription and non-prescription medications, herbal remedies, or vitamin supplements within 14 days prior to the first dosing. Thyroid hormone replacement medication may be permitted if the participant has been on the same stable dose for the immediate 3 months prior to first dosing. * Any drugs known to be significant inducers of cytochrome P450 (CYP)3A, CYP2C19, uridine 5' diphospho-glucuronosyltransferase (UGT)1A9 or (UGT)2B4 enzymes and/or P-glycoprotein (P-gp), including St. John's Wort, within 28 days prior to the first dosing. Appropriate sources (example, Flockhart TableTM) will be consulted to confirm lack of Pharmacokinetics (PK)/pharmacodynamics interaction with study drug. 7. Consumes excessive amounts, defined as greater than 4 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks or other caffeinated beverages per day.

Outcomes

Primary Outcomes

Placebo-corrected Change From Baseline in Corrected QT Interval (QTc)

The QTc interval will be measured by continuous electrocardiogram (ECG) recordings. The primary QT correction method will be Fridericia's correction. In case a substantial HR effect is observed on-treatment with soticlestat, drug-free QT/RR data will be collected over a range of Heart Rate (HR) seen off-treatment to allow the generation of individualized QT correction methods. QTc will be calculated from Day -1 of the first treatment period both during the periods of supine rest (QTcS) and from all evaluable QT/RR pairs in the 24-hour recording (QTcI). The method that removes the HR dependence of the QT interval most efficiently will be chosen as primary correction method. The analysis for QTc will be based on a linear mixed-effects model with ΔQTc as the dependent variable, period, sequence, time (that is, nominal post-dose time point), treatment, and time-by-treatment interaction as fixed effects, and baseline QTc as a covariate.

Time frame: Day -1 up to 24 hours post-dose

Secondary Outcomes

Change From Baseline in HR

HR will be measured by continuous ECG recordings.

Time frame: Day 1: Pre-dose up to 24 hours post-dose

Change From Baseline in QTc With the Methods Not Selected as Primary

The QTc interval will be measured by continuous ECG recordings. Pre-dose will be the average of the derived ECG intervals from the 3 ECG time-points (-0.75, -0.5, and -0.25 hours) prior to treatment administration on Day 1 within each respective period.

Time frame: Day 1: Pre-dose up to 24 hours post-dose

Change From Baseline in Individualized HR-corrected QT interval (QTcS)

The QTcS interval will be measured by continuous ECG recordings and QT/RR interval of ECG (RR) data obtained at supine resting time points. The analysis for QTcS will be based on a linear mixed-effects model.

Time frame: Day 1: Pre-dose up to 24 hours post-dose

Data from ClinicalTrials.gov

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