A Study to Assess S-309309 in Healthy and Obese Participants

Study Overview
=================
Brief Summary
-----------------
The primary aim of the study is to assess the safety and tolerability of S-309309 after oral administration in healthy adult or obese but otherwise healthy adult participants. The secondary aim of the study is to assess the pharmacokinetics of S-309309 and the effects on ECG parameters after oral administration in healthy or obese but otherwise healthy participants.

Detailed Description
-----------------
This study will consist of 2 Parts. Part 1 will include healthy participants who will be assigned to a dose group. Participants will then be randomized to receive a single oral administration of S-309309 or placebo in a fasted state. Administration will be initiated in the lowest dose group, and administration in the next dose group will not occur until a review of safety and tolerability has been completed for the preceding group. Part 2 will include 2 groups. Healthy participants and obese but otherwise healthy participants will receive multiple oral administrations of S-309309 or placebo in a fed state.

Official Title
-----------------
A Phase 1 Randomized, Double-blind, Single and Multiple-dose Study to Assess the Safety, Tolerability, Pharmacokinetics, Food Effect, and Drug-Drug Interactions of S-309309 in Healthy and Obese Adult Study Participants

Conditions
-----------------
Obesity

Intervention / Treatment
-----------------
* Drug: S-309309
* Drug: Midazolam
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy as determined by medical evaluation including medical history, physical examination, clinical laboratory tests, vital sign measurements, and 12-lead ECG at the Screening Visit and upon admission to the clinical research unit (CRU). Body weight ≥50 kilograms (kg), and body mass index (BMI) within the range ≥18.5 to <30.0 kilogram/meter square (kg/m^2) for all groups except Group G-2. For Group G-2, BMI ≥ 30 to < 40 kg/m2 at the Screening Visit. Exclusion Criteria: History or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data. Lymphoma, leukemia, or any malignancy within the past 5 years, except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years. Breast cancer within the past 10 years. Unable to swallow capsules. Chronic history of or current liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: S-309309<br>Participants will receive S-309309 at specific timepoints in a fasted state. | Drug: S-309309<br>* Capsule administered orally<br>|
| Experimental: Part 2: S-309309 and Midazolam<br>Participants will receive S-309309 and Midazolam at specific timepoints fed state. | Drug: S-309309<br>* Capsule administered orally<br>Drug: Midazolam<br>* Syrup administered orally<br>|
| Placebo Comparator: Part 1 and 2: Placebo<br>Participants will receive a matching placebo to S-309309 at specific timepoints in either a fed or fasted state. | Drug: Placebo<br>* Matching capsule to S-309309 administered orally<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 and 2: Number of Participants with Treatment Emergent Adverse Events (TEAEs) |  | Up to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Maximum Plasma Concentration (Cmax) of S-309309 |  | 0 (predose) up to 144 hours postdose on Day 1 to Day 21 | 
| Part 1: Time to Maximum Plasma Concentration (Tmax) of S-309309 |  | 0 (predose) up to 144 hours postdose on Day 1 to Day 21 | 
| Part 1: Area Under the Plasma Concentration-Time Curve (AUC) of S-309309 |  | 0 (predose) up to 144 hours postdose on Day 1 to Day 21 | 
| Part 1: Terminal Elimination Half-Life (t1/2,z) of S-309309 |  | 0 (predose) up to 144 hours postdose on Day 1 to Day 21 | 
| Part 1: Terminal Elimination Rate Constant (λz) of S-309309 |  | 0 (predose) up to 144 hours postdose on Day 1 to Day 21 | 
| Part 1: Mean Residence Time (MRT) of S-309309 |  | 0 (predose) up to 144 hours postdose on Day 1 to Day 21 | 
| Part 1: Apparent Total Clearance (CL/F) of S-309309 |  | 0 (predose) up to 144 hours postdose on Day 1 to Day 21 | 
| Part 1: Apparent Volume of Distribution (Vz/F) of S-309309 |  | 0 (predose) up to 144 hours postdose on Day 1 to Day 21 | 
| Part 1: Renal Clearance (CLR) of S-309309 |  | 0 (predose) up to 144 hours postdose on Day 1 to Day 21 | 
| Part 1: Fraction of Dose Excreted in Urine (Feu) of S-309309 |  | 0 (predose) up to 144 hours postdose on Day 1 to Day 21 | 
| Part 1: Change From Baseline of Electrocardiogram (ECG) Parameters: QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF), Pulse Rate (PR) Interval, and Combination of the Q, R, and S Waves (QRS) Duration |  | Baseline, Day 2, 5, 7 and 16 | 
| Part 1: Change From Baseline of ECG Parameter: Heart Rate (HR) |  | Baseline, Day 2, 3, 4, 5, 6, 7 and 16 | 
| Part 1: Placebo-Corrected Change From Baseline of ECG Parameters: QTcF, PR Interval, and QRS Duration |  | Baseline, Day 2, 5, 7 and 16 | 
| Part 1: Placebo-Corrected Change From Baseline of ECG Parameter: HR |  | Baseline, Day 2, 3, 4, 5, 6, 7 and 16 | 
| Part 1: Number of Participants With Categorical Outlier Values for HR, QTcF, PR, and QRS |  | Baseline up to Day 16 | 
| Part 1: Number of Participants With Treatment-Emergent Changes for T-wave Morphology and Presence of U-wave |  | Baseline up to Day 16 | 
| Part 2: Cmax of S-309309 and Midazolam |  | 0 (predose) up to 24 hours postdose on Day -2 to Day 16 | 
| Part 2: Tmax of S-309309 and Midazolam |  | 0 (predose) up to 24 hours postdose on Day -2 to Day 16 | 
| Part 2: AUC of S-309309 and Midazolam |  | 0 (predose) up to 24 hours postdose on Day -2 to Day 16 | 
| Part 2: t1/2,z of S-309309 and Midazolam |  | 0 (predose) up to 24 hours postdose on Day -2 to Day 16 | 
| Part 2: λz of S-309309 and Midazolam |  | 0 (predose) up to 24 hours postdose on Day -2 to Day 16 | 
| Part 2: CL/F of S-309309 and Midazolam |  | 0 (predose) up to 24 hours postdose on Day -2 to Day 16 | 
| Part 2: Vz/F of S-309309 and Midazolam |  | 0 (predose) up to 24 hours postdose on Day -2 to Day 16 | 
| Part 2: MRT of Midazolam |  | 0 (predose) up to 24 hours postdose on Day -2 to Day 16 | 
| Part 2: Number of Participants with TEAEs After Coadministration with Midazolam |  | Up to Day 28 |