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

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: S-309309; Drug: Midazolam; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78209
      • ICON Early Phase Services, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Shionogi

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2022
• Primary Completion (Actual): October 20, 2022
• Study Completion (Actual): November 1, 2022

Study Registration Dates

• First Submitted: February 8, 2022
• First Submitted That Met QC Criteria: February 8, 2022
• First Posted (Actual): February 21, 2022

Study Record Updates

• Last Update Posted (Estimate): January 11, 2023
• Last Update Submitted That Met QC Criteria: January 10, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: 2018N1111

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No