A Study of Soticlestat Tablets in Healthy Adults

A Phase 1, Open-Label, Randomized, Crossover Study to Evaluate the Bioequivalence of Soticlestat Oral Tablet Formulations and the Effect of Food and Tablet Crushing on the Pharmacokinetics of Soticlestat in Healthy Adult Participants

The main aim is to see how soticlestat tablets of different strengths work and to compare how it works alone in contrast to administration along with food.

In the study will be 2 groups of participants (part A and part B). Participants in part A will receive 300 mg of soticlestat administered in different kind of tablets (regular tablets, mini-tablets, commercial tablets) and participant in part B will also receive 300 mg of soticlestat in tablets but with food and crushed tablets with applesauce.

Participants will complete several assessments including clinical laboratory evaluations, physical examinations, Columbia-Suicide Severity Rating Scale (C-SSRS) assessment, electrocardiographs (ECGs), and vital signs.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Soticlestat; Drug: Soticlestat; Drug: Soticlestat

Detailed Description

The drug being tested in this study is called soticlestat (TAK-935). The study will assess the bioequivalence, effect of food and tablet crushing, safety and tolerability following single oral dose of 3 different soticlestat oral tablet formulations in healthy participants.

The study will enroll approximately 96 participants. This study will be conducted in two parts (Part A and Part B) having 6 treatment sequences each. Participants will be randomly assigned (by chance, like flipping a coin) to one of the study parts as per treatment sequence:

• Part A, Sequence 1: Treatment A + Treatment B + Treatment C
• Part A, Sequence 2: Treatment A + Treatment C + Treatment B
• Part A, Sequence 3: Treatment B + Treatment A + Treatment C
• Part A, Sequence 4: Treatment B + Treatment C + Treatment A
• Part A, Sequence 5: Treatment C + Treatment A + Treatment B
• Part A, Sequence 6: Treatment C + Treatment B + Treatment A
• Part B, Sequence 1: Treatment D + Treatment E + Treatment F
• Part B, Sequence 2: Treatment D + Treatment F + Treatment E
• Part B, Sequence 3: Treatment E + Treatment D + Treatment F
• Part B, Sequence 4: Treatment E + Treatment F + Treatment D
• Part B, Sequence 5: Treatment F + Treatment D + Treatment E
• Part B, Sequence 6: Treatment F + Treatment E + Treatment D

This single center trial will be conducted in the United States. The overall duration of the study is approximately 51 days. Participants will be followed up for 14 days after the last dose of study drug for a follow-up assessment.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

1. Body mass index (BMI) greater than or equal to (>=) 18.0 and less than or equal to (<=) 32.0 kilogram per square meter (kg/m^2) at screening.
2. Continuous non-smoker who has not used nicotine-containing products for at least 90 days prior to the first dosing.
3. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, and ECGs, as deemed by the Investigator or designee.
4. Able to swallow multiple tablets.

Key Exclusion Criteria:

1. History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.
2. Positive urine drug or alcohol results at screening or check-in.
3. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).

4. Unable to refrain from or anticipates the use of:

   • Any drug, 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 the first dosing.
   • Any drugs known to be significant inducers of cytochrome P450 (CYP) 3A, CYP2C19, uridine 5'-diphospho-glucuronosyltransferase (UGT) 1A9 or UGT2B4 enzymes and/or P-glycoprotein (P-gp), including St. John's Wort, within 28 days prior to the first dosing. Appropriate sources will be consulted to confirm lack of PK/pharmacodynamics interaction with study drug.
5. History of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to the following: beer [354 milliliter per 12 ounce {mL/12 oz}], wine [118 mL/4 oz], or distilled spirits [29.5 mL/1 oz] per day).
6. Consumes excessive amounts, defined as greater than 4 servings (1 serving is approximately equivalent to 120mg of caffeine), of coffee, tea, cola, energy drinks, or other caffeinated beverages per day.
7. 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 the first dosing and throughout the study.
8. Donation of blood or significant blood loss within 56 days prior to the first dosing.
9. Plasma donation within 7 days prior to the first dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A, Sequence 2: Treatment A + Treatment C + Treatment B; Soticlestat T4 tablets 300 mg, orally, once on Day 1 of Period 1 under fasted condition as Treatment A, followed by soticlestat T3 commercial tablets 300 mg, orally, once on Day 1 of Period 2 under fasted condition as Treatment C, and followed by soticlestat T3 mini-tablets 300 mg, orally, once on Day 1 of Period 3 under fasted condition as Treatment B. A washout interval of exactly 4 days will be maintained between each Treatment Period.	Drug: Soticlestat; Soticlestat T4 tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat T3 mini-tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat commercial tablets.; Other Names: TAK-935
Experimental: Part A, Sequence 4: Treatment B + Treatment C + Treatment A; Soticlestat T3 mini-tablets 300 mg, orally, once on Day 1 of Period 1 under fasted condition as Treatment B, followed by soticlestat T3 commercial tablets 300 mg, orally, once on Day 1 of Period 2 under fasted condition as Treatment C, and followed by soticlestat T4 300 mg, tablets, orally, once on Day 1 of Period 3 under fasted condition as Treatment A. A washout interval of exactly 4 days will be maintained between each Treatment Period.	Drug: Soticlestat; Soticlestat T4 tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat T3 mini-tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat commercial tablets.; Other Names: TAK-935
Experimental: Part B, Sequence 2: Treatment D + Treatment F + Treatment E; Soticlestat T4 300 mg, tablets, orally, once on Day 1 of Period 1 under fasted condition as Treatment D, followed by soticlestat T4 300 mg, tablets crushed and mixed with applesauce, orally, once on Day 1 of Period 2 under fasted condition as Treatment F, and followed by soticlestat T4 300 mg, orally, once on Day 1 of Period 3 under fed condition as Treatment E. A washout interval of exactly 4 days will be maintained between each Treatment Period.	Drug: Soticlestat; Soticlestat T4 tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat T3 mini-tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat commercial tablets.; Other Names: TAK-935
Experimental: Part B, Sequence 3: Treatment F + Treatment E + Treatment D; Soticlestat T4 300 mg tablets, crushed and mixed with applesauce, orally, once on Day 1 of Period 1 under fasted condition as Treatment F, followed by soticlestat T4 300 mg, tablets, orally, once on Day 1 of Period 2 under fed condition as Treatment E, and followed by soticlestat T4 300 mg tablets, orally, once on Day 1 of Period 3 under fasted condition as Treatment D. A washout interval of exactly 4 days will be maintained between each Treatment Period.	Drug: Soticlestat; Soticlestat T4 tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat T3 mini-tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat commercial tablets.; Other Names: TAK-935
Experimental: Part B, Sequence 4: Treatment E + Treatment F + Treatment D; Soticlestat T4 300 mg, tablets, orally, once on Day 1 of Period 1 under fed condition as Treatment E, followed by soticlestat T4 300 mg tablets crushed and mixed with applesauce, orally, once on Day 1 of Period 2 under fasted condition as Treatment F, and followed by soticlestat T4 300 mg, tablets, orally, once on Day 1 of Period 3 under fasted condition as Treatment D. A washout interval of exactly 4 days will be maintained between each Treatment Period.	Drug: Soticlestat; Soticlestat T4 tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat T3 mini-tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat commercial tablets.; Other Names: TAK-935
Experimental: Part A, Sequence 1: Treatment A + Treatment B + Treatment C; Soticlestat T4 tablets 300 mg, orally, once on Day 1 of Period 1 under fasted condition as Treatment A, followed by soticlestat T3 mini-tablets 300 mg, orally, once on Day 1 of Period 2 under fasted condition as Treatment B, and followed by soticlestat T3 commercial tablets 300 mg, orally, once on Day 1 of Period 3 under fasted condition as Treatment C. A washout interval of exactly 4 days will be maintained between each Treatment Period.	Drug: Soticlestat; Soticlestat T4 tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat T3 mini-tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat commercial tablets.; Other Names: TAK-935
Experimental: Part A, Sequence 3: Treatment B + Treatment A + Treatment C; Soticlestat T3 mini-tablets 300 milligram (mg), orally, once on Day 1 of Period 1 under fasted condition as Treatment B, followed by soticlestat T4 300 mg, tablets, orally, once on Day 1 of Period 2 under fasted condition as Treatment A, and followed by soticlestat T3 commercial tablets 300 mg, orally, once on Day 1 of Period 3 under fasted condition as Treatment C. A washout interval of exactly 4 days will be maintained between each Treatment Period.	Drug: Soticlestat; Soticlestat T4 tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat T3 mini-tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat commercial tablets.; Other Names: TAK-935
Experimental: Part A, Sequence 5: Treatment C + Treatment A + Treatment B; Soticlestat T3 commercial tablets 300 mg, orally, once on Day 1 of Period 1 under fasted condition as Treatment C, followed by soticlestat T4 300 mg, tablets, orally, once on Day 1 of Period 2 under fasted condition as Treatment A, and followed by soticlestat T3 mini-tablets 300 mg, orally, once on Day 1 of Period 3 under fasted condition as Treatment B. A washout interval of exactly 4 days will be maintained between each Treatment Period.	Drug: Soticlestat; Soticlestat T4 tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat T3 mini-tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat commercial tablets.; Other Names: TAK-935
Experimental: Part A, Sequence 6: Treatment C + Treatment B + Treatment A; Soticlestat T3 commercial tablets 300 mg, orally, once on Day 1 of Period 1 under fasted condition as Treatment C, followed by soticlestat T3 mini-tablets 300 mg, tablets, orally, once on Day 1 of Period 2 under fasted condition as Treatment B, and followed by soticlestat T4 tablets 300 mg, orally, once on Day 1 of Period 3 under fasted condition as Treatment A. A washout interval of exactly 4 days will be maintained between each Treatment Period.	Drug: Soticlestat; Soticlestat T4 tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat T3 mini-tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat commercial tablets.; Other Names: TAK-935
Experimental: Part B, Sequence 1: Treatment D + Treatment E + Treatment F; Soticlestat T4 300 mg, tablets, orally, once on Day 1 of Period 1 under fasted condition as Treatment D, followed by soticlestat T4 300 mg, tablets, orally, once on Day 1 of Period 2 under fed condition as Treatment E, and followed by soticlestat T4 300 mg tablets crushed and mixed with applesauce, orally, once on Day 1 of Period 3 under fasted condition as Treatment F. A washout interval of exactly 4 days will be maintained between each Treatment Period.	Drug: Soticlestat; Soticlestat T4 tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat T3 mini-tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat commercial tablets.; Other Names: TAK-935
Experimental: Part B, Sequence 3: Treatment E + Treatment D + Treatment F; Soticlestat T4 300 mg, tablets, orally, once on Day 1 of Period 1 under fed condition as Treatment E, followed by soticlestat T4 300 mg, tablets, orally, once on Day 1 of Period 2 under fasted condition as Treatment D, and followed by soticlestat T4 300 mg, tablets crushed and mixed with applesauce, orally, once on Day 1 of Period 3 under fasted condition as Treatment F. A washout interval of exactly 4 days will be maintained between each Treatment Period.	Drug: Soticlestat; Soticlestat T4 tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat T3 mini-tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat commercial tablets.; Other Names: TAK-935
Experimental: Part B, Sequence 5: Treatment F + Treatment D + Treatment E; Soticlestat T4 300 mg tablets crushed and mixed with applesauce, orally, once on Day 1 of Period 1 under fasted condition as Treatment F, followed by soticlestat T4 300 mg, tablets, orally, once on Day 1 of Period 2 under fasted condition as Treatment D, and followed by soticlestat T4 300 mg, tablets, orally, once on Day 1 of Period 3 under fed condition as Treatment E. A washout interval of exactly 4 days will be maintained between each Treatment Period.	Drug: Soticlestat; Soticlestat T4 tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat T3 mini-tablets.; Other Names: TAK-935; Drug: Soticlestat; Soticlestat commercial tablets.; Other Names: TAK-935

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax: Maximum Observed Plasma Concentration for Soticlestat	Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
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 time points (up to 96 hours) post-dose
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Soticlestat	Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.	From screening up to 14 days after the last dose of soticlestat (Day 51)

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2022
• Primary Completion (Actual): May 22, 2022
• Study Completion (Actual): June 2, 2022

Study Registration Dates

• First Submitted: March 10, 2022
• First Submitted That Met QC Criteria: March 10, 2022
• First Posted (Actual): March 17, 2022

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Drug Therapy
• Other Study ID Numbers: TAK-935-1014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No