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

NCT05309902 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: TAK-935-1001
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Healthy Volunteers

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• 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.

  Day -1 up to 24 hours post-dose

Secondary Outcomes (21)

• Change From Baseline in HR

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

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

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

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

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

• Change From Baseline in Optimized QT Interval (QTcI)

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

• Change From Baseline in PR Interval of the ECG (PR)

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

Study Arms (4)

Sequence 1: (Regimen A + Regimen B + Regimen C + Regimen D)

EXPERIMENTAL

Regimen A (soticlestat 300 milligram \[mg\] tablets + soticlestat placebo-matching tablets + moxifloxacin placebo-matching capsule), orally, in fasting condition once on Day 1 of Treatment Period 1, followed by at least 7 days washout period, followed by Regimen B (soticlestat 900 mg tablets + moxifloxacin placebo-matching capsule), orally, in fasting condition once on Day 1 of Treatment Period 2, followed by at least 7 days washout period, followed by Regimen C (soticlestat placebo-matching tablets + moxifloxacin 400 mg over-encapsulated tablet), orally, in fasting condition, once on Day 1 of Treatment Period 3, followed by at least 7 days washout period, followed by Regimen D (soticlestat placebo-matching tablets + moxifloxacin placebo-matching capsule), orally, in fasting condition once on Day 1 of Treatment Period 4.

Drug: Soticlestat; Drug: Placebo; Drug: Moxifloxacin

Sequence 2: (Regimen B + Regimen D + Regimen A + Regimen C)

EXPERIMENTAL

Regimen B (soticlestat 900 mg tablets + moxifloxacin placebo-matching capsule), orally, in fasting condition once on Day 1 of Treatment Period 1, followed by at least 7 days washout period, followed by Regimen D (soticlestat placebo-matching tablets + moxifloxacin placebo-matching capsule), orally, in fasting condition once on Day 1 of Treatment Period 2, followed by at least 7 days washout period, followed by Regimen A (soticlestat 300 mg tablets + soticlestat placebo-matching tablets + moxifloxacin placebo-matching capsule), orally, in fasting condition, once on Day 1 of Treatment Period 3, followed by at least 7 days washout period, followed by Regimen C (soticlestat -matching tablets + moxifloxacin 400 mg over-encapsulated tablet), orally, in fasting condition once on Day 1 of Treatment Period 4.

Drug: Soticlestat; Drug: Placebo; Drug: Moxifloxacin

Sequence 3: (Regimen C + Regimen A + Regimen D + Regimen B)

EXPERIMENTAL

Regimen C (soticlestat placebo-matching tablets + moxifloxacin 400 mg over-encapsulated tablet), orally, in fasting condition once on Day 1 of Treatment Period 1, followed by at least 7 days washout period, followed by Regimen A (soticlestat 300 mg tablets + soticlestat placebo-matching tablets + moxifloxacin placebo-matching capsule), orally, in fasting condition once on Day 1 of Treatment Period 2, followed by at least 7 days washout period, followed by Regimen D (soticlestat placebo-matching tablets + moxifloxacin placebo-matching capsule), orally, in fasting condition, once on Day 1 of Treatment Period 3, followed by at least 7 days washout period, followed by Regimen B (soticlestat 900 mg tablets + moxifloxacin placebo-matching capsule), orally, in fasting condition once on Day 1 of Treatment Period 4.

Drug: Soticlestat; Drug: Placebo; Drug: Moxifloxacin

Sequence 4: (Regimen D + Regimen C + Regimen B + Regimen A)

EXPERIMENTAL

Regimen D (soticlestat placebo-matching tablets + moxifloxacin placebo-matching capsule), orally, in fasting condition once on Day 1 of Treatment Period 1, followed by at least 7 days washout period, followed by Regimen C (soticlestat placebo-matching tablets + moxifloxacin 400 mg over-encapsulated tablet), orally, in fasting condition once on Day 1 of Treatment Period 2, followed by at least 7 days washout period, followed by Regimen B (soticlestat 900 mg tablets + moxifloxacin placebo-matching capsule), orally, in fasting condition, once on Day 1 of Treatment Period 3, followed by at least 7 days washout period, followed by Regimen A (soticlestat 300 mg tablets + soticlestat placebo-matching tablets + moxifloxacin placebo-matching capsule), orally, in fasting condition once on Day 1 of Treatment Period 4.

Drug: Soticlestat; Drug: Placebo; Drug: Moxifloxacin

Interventions

Soticlestat DRUG

Soticlestat tablet.

Also known as: TAK-935

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)

Placebo DRUG

Soticlestat placebo-matching tablet.

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)

Moxifloxacin DRUG

Moxifloxacin over-encapsulated tablet.

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)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male participants agree to comply with any applicable contraceptive requirements of the protocol.
• Body mass index (BMI) greater than or equal to (\>=)18.0 and \<=32.0 kilogram per square meter (kg/m\^2) at screening.
• 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.
• 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.

You may not qualify if:

• Mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
• 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.
• 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.
• Positive urine drug or alcohol results at screening or at check-in.
• Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or antibody test for hepatitis C virus (HCV).
• 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.

Sponsors & Collaborators

• Takeda: lead

Related Links

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

MeSH Terms

Interventions

soticlestat; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2022
• First Posted: April 4, 2022
• Study Start: October 11, 2022
• Primary Completion: December 6, 2022
• Study Completion: December 6, 2022
• Last Updated: November 14, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.