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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05309902
• Other study ID #: TAK-935-1001
• Status: Withdrawn
• Phase: Phase 1
• Start date: October 11, 2022
• Est. completion date: December 6, 2022

Study information

• Verified date: November 2022
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 6, 2022
• Est. primary completion date: December 6, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Soticlestat
Soticlestat tablet.
• Placebo
Soticlestat placebo-matching tablet.
• Moxifloxacin
Moxifloxacin over-encapsulated tablet.
• Placebo
Moxifloxacin placebo-matching capsule.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 ?QTc 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	Change From Baseline in HR	HR will be measured by continuous ECG recordings.	Day 1: Pre-dose up to 24 hours post-dose
Secondary	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.	Day 1: Pre-dose up to 24 hours post-dose
Secondary	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.	Day 1: Pre-dose up to 24 hours post-dose
Secondary	Change From Baseline in Optimized QT Interval (QTcI)	The QTcI interval will be measured by continuous ECG recordings and QT/RR data obtained at supine resting time points. The analysis for QTcI will be based on a linear regression model.	Day 1: Pre-dose up to 24 hours post-dose
Secondary	Change From Baseline in PR Interval of the ECG (PR)	PR will be measured by continuous ECG recordings.	Day 1: Pre-dose up to 24 hours post-dose
Secondary	Change From Baseline in QRS Interval of the ECG (QRS)	QRS will be measured by continuous ECG recordings.	Day 1: Pre-dose up to 24 hours post-dose
Secondary	Placebo-corrected Change From Baseline in HR	Placebo-corrected HR will be measured by continuous ECG recordings.	Day 1: Pre-dose up to 24 hours post-dose
Secondary	Placebo-corrected Change From Baseline in QTc With the Methods Not Selected as Primary	Placebo-corrected 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.	Day 1: Pre-dose up to 24 hours post-dose
Secondary	Placebo-corrected Change From Baseline in PR Interval of ECG	Placebo-corrected PR interval will be measured by continuous ECG recordings.	Day 1: Pre-dose up to 24 hours post-dose
Secondary	Placebo-corrected Change From Baseline in QRS Interval of ECG	Placebo-corrected QRS interval will be measured by continuous ECG recordings.	Day 1: Pre-dose up to 24 hours post-dose
Secondary	Number of Participants with Categorical Outlier Values for HR	Number of participants with categorical outlier values for HR will be determined. A participant will be determined as an outlier if the following criteria were met for the ECG intervals at any time point: Decrease of HR from baseline greater than (>) 25 percent (%) resulting in HR less than (<) 50 beats per minute (bpm) and increase in HR from baseline resulting in HR >100 bpm.	Day 1: Pre-dose up to 24 hours post-dose
Secondary	Number of Participants with Categorical Outliers Values for PR	Number of participants with categorical outlier values for PR will be determined. A participant will be determined as an outlier if the following criteria were met for the ECG interval at any time point: Increase of PR from Baseline >25% resulting in PR >200 millisecond (ms).	Day 1: Pre-dose up to 24 hours post-dose
Secondary	Number of Participants with Categorical Outliers Values for QRS	Number of participants with categorical outliers values for QRS will be determined. A participant will be determined as an outlier if the following criteria were met for the ECG interval at any time point: Increase of QRS from Baseline >25% resulting in QRS >120 ms.	Day 1: Pre-dose up to 24 hours post-dose
Secondary	Number of Participants with Categorical Outliers Values for QTc	Number of participants with categorical outliers values for QTc will be determined. A participant will be determined as an outlier if the following criteria were met for the ECG interval at any time point: Increase in treatment-emergent value >450 and less than or equal to (<=) 480 ms; >480 and <=500; change from Baseline of >30 and <=60 ms or >60 ms.	Day 1: Pre-dose up to 24 hours post-dose
Secondary	Percentage of Participants with Change From Baseline in ECG Morphology	ECG morphological analyses will be performed using the ECG waveform interpretation as defined by the central ECG laboratory's cardiologist.	Day 1: Pre-dose up to 24 hours post-dose
Secondary	Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs)	An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant who has signed informed consent to participate in a study; it does not necessarily have to have a causal relationship with the treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.	Baseline (Day 1) up to 14 days after the last dose of study drug in Period 4 (Day 39)
Secondary	Cmax: Maximum Observed Plasma Concentration for Soticlestat		Day 1: Pre-dose and at multiple timepoints (up to 24 hours) post-dose
Secondary	AUC8: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Soticlestat		Day 1: Pre-dose and at multiple timepoints (up to 24 hours) post-dose
Secondary	AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Soticlestat		Day 1: Pre-dose and at multiple timepoints (up to 24 hours) post-dose
Secondary	Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Soticlestat		Day 1: Pre-dose and at multiple timepoints (up to 24 hours) post-dose
Secondary	T1/2z: Terminal Phase Elimination Half-life for Soticlestat		Day 1: Pre-dose and at multiple timepoints (up to 24 hours) post-dose

External Links

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