Clinical trial NCT05309902: A Study of Soticlestat in Healthy Adults To Evaluate the Effect on QTc Interval
Official title: A Phase 1, Double-Blinded, Placebo- and Active-Controlled, Randomized Study to Investigate the Potential of Soticlestat to Prolong the QTc Interval in Healthy Adult Participants
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2022-04-04
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Placebo-corrected Change From Baseline in Corrected QT Interval (QTc)
timeFrame: Day -1 up to 24 hours post-dose
Secondary outcomes:
measure: Change From Baseline in HR
timeFrame: Day 1: Pre-dose up to 24 hours post-dose
measure: Change From Baseline in QTc With the Methods Not Selected as Primary
timeFrame: Day 1: Pre-dose up to 24 hours post-dose
measure: Change From Baseline in Individualized HR-corrected QT interval (QTcS)
timeFrame: Day 1: Pre-dose up to 24 hours post-dose
measure: Change From Baseline in Optimized QT Interval (QTcI)
timeFrame: Day 1: Pre-dose up to 24 hours post-dose
measure: Change From Baseline in PR Interval of the ECG (PR)
timeFrame: Day 1: Pre-dose up to 24 hours post-dose
measure: Change From Baseline in QRS Interval of the ECG (QRS)
timeFrame: Day 1: Pre-dose up to 24 hours post-dose
measure: Placebo-corrected Change From Baseline in HR
timeFrame: Day 1: Pre-dose up to 24 hours post-dose
measure: Placebo-corrected Change From Baseline in QTc With the Methods Not Selected as Primary
timeFrame: Day 1: Pre-dose up to 24 hours post-dose
measure: Placebo-corrected Change From Baseline in PR Interval of ECG
timeFrame: Day 1: Pre-dose up to 24 hours post-dose
measure: Placebo-corrected Change From Baseline in QRS Interval of ECG
timeFrame: Day 1: Pre-dose up to 24 hours post-dose
measure: Number of Participants with Categorical Outlier Values for HR
timeFrame: Day 1: Pre-dose up to 24 hours post-dose
measure: Number of Participants with Categorical Outliers Values for PR
timeFrame: Day 1: Pre-dose up to 24 hours post-dose
measure: Number of Participants with Categorical Outliers Values for QRS
timeFrame: Day 1: Pre-dose up to 24 hours post-dose
measure: Number of Participants with Categorical Outliers Values for QTc
timeFrame: Day 1: Pre-dose up to 24 hours post-dose
measure: Percentage of Participants with Change From Baseline in ECG Morphology
timeFrame: Day 1: Pre-dose up to 24 hours post-dose
measure: Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline (Day 1) up to 14 days after the last dose of study drug in Period 4 (Day 39)
measure: Cmax: Maximum Observed Plasma Concentration for Soticlestat
timeFrame: Day 1: Pre-dose and at multiple timepoints (up to 24 hours) post-dose
measure: AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Soticlestat
timeFrame: Day 1: Pre-dose and at multiple timepoints (up to 24 hours) post-dose
measure: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Soticlestat
timeFrame: Day 1: Pre-dose and at multiple timepoints (up to 24 hours) post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Soticlestat
timeFrame: Day 1: Pre-dose and at multiple timepoints (up to 24 hours) post-dose
measure: T1/2z: Terminal Phase Elimination Half-life for Soticlestat
timeFrame: Day 1: Pre-dose and at multiple timepoints (up to 24 hours) post-dose
Other outcomes:
Locations:
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: