A Study of Soticlestat Tablets in Healthy Adults

Study Overview
=================
Brief Summary
-----------------
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.

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

Official Title
-----------------
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

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: Soticlestat
* Drug: Soticlestat
* Drug: Soticlestat


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: 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. Continuous non-smoker who has not used nicotine-containing products for at least 90 days prior to the first dosing. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, and ECGs, as deemed by the Investigator or designee. Able to swallow multiple tablets. Key Exclusion Criteria: History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing. Positive urine drug or alcohol results at screening or check-in. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV). 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. 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). 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. 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. Donation of blood or significant blood loss within 56 days prior to the first dosing. Plasma donation within 7 days prior to the first dosing.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A, Sequence 1: Treatment B + Treatment A + Treatment C<br>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<br>* Soticlestat T4 tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat T3 mini-tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat commercial tablets.<br>* Other names: TAK-935;|
| Experimental: Part A, Sequence 2: Treatment A + Treatment C + Treatment B<br>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<br>* Soticlestat T4 tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat T3 mini-tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat commercial tablets.<br>* Other names: TAK-935;|
| Experimental: Part A, Sequence 3: Treatment C + Treatment B + Treatment A<br>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<br>* Soticlestat T4 tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat T3 mini-tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat commercial tablets.<br>* Other names: TAK-935;|
| Experimental: Part A, Sequence 4: Treatment B + Treatment C + Treatment A<br>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<br>* Soticlestat T4 tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat T3 mini-tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat commercial tablets.<br>* Other names: TAK-935;|
| Experimental: Part A, Sequence 5: Treatment A + Treatment B + Treatment C<br>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<br>* Soticlestat T4 tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat T3 mini-tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat commercial tablets.<br>* Other names: TAK-935;|
| Experimental: Part A, Sequence 6: Treatment C + Treatment A + Treatment B<br>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<br>* Soticlestat T4 tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat T3 mini-tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat commercial tablets.<br>* Other names: TAK-935;|
| Experimental: Part B, Sequence 1: Treatment E + Treatment D + Treatment F<br>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<br>* Soticlestat T4 tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat T3 mini-tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat commercial tablets.<br>* Other names: TAK-935;|
| Experimental: Part B, Sequence 2: Treatment D + Treatment F + Treatment E<br>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<br>* Soticlestat T4 tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat T3 mini-tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat commercial tablets.<br>* Other names: TAK-935;|
| Experimental: Part B, Sequence 3: Treatment F + Treatment E + Treatment D<br>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<br>* Soticlestat T4 tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat T3 mini-tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat commercial tablets.<br>* Other names: TAK-935;|
| Experimental: Part B, Sequence 4: Treatment E + Treatment F + Treatment D<br>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<br>* Soticlestat T4 tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat T3 mini-tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat commercial tablets.<br>* Other names: TAK-935;|
| Experimental: Part B, Sequence 5: Treatment D + Treatment E + Treatment F<br>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<br>* Soticlestat T4 tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat T3 mini-tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat commercial tablets.<br>* Other names: TAK-935;|
| Experimental: Part B, Sequence 6: Treatment F + Treatment D + Treatment E<br>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<br>* Soticlestat T4 tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat T3 mini-tablets.<br>* Other names: TAK-935;Drug: Soticlestat<br>* Soticlestat commercial tablets.<br>* Other names: TAK-935;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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) |  | From screening up to 14 days after the last dose of soticlestat (Day 51) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Drug Therapy