Clinical trial NCT05247970: A Study to Assess S-309309 in Healthy and Obese Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Obesity
Lead sponsor: Shionogi Inc.
Sponsor class: INDUSTRY
First posted: 2022-02-21
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Part 1 and 2: Number of Participants with Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to Day 28
Secondary outcomes:
measure: Part 1: Maximum Plasma Concentration (Cmax) of S-309309
timeFrame: 0 (predose) up to 144 hours postdose on Day 1 to Day 21
measure: Part 1: Time to Maximum Plasma Concentration (Tmax) of S-309309
timeFrame: 0 (predose) up to 144 hours postdose on Day 1 to Day 21
measure: Part 1: Area Under the Plasma Concentration-Time Curve (AUC) of S-309309
timeFrame: 0 (predose) up to 144 hours postdose on Day 1 to Day 21
measure: Part 1: Terminal Elimination Half-Life (t1/2,z) of S-309309
timeFrame: 0 (predose) up to 144 hours postdose on Day 1 to Day 21
measure: Part 1: Terminal Elimination Rate Constant (λz) of S-309309
timeFrame: 0 (predose) up to 144 hours postdose on Day 1 to Day 21
measure: Part 1: Mean Residence Time (MRT) of S-309309
timeFrame: 0 (predose) up to 144 hours postdose on Day 1 to Day 21
measure: Part 1: Apparent Total Clearance (CL/F) of S-309309
timeFrame: 0 (predose) up to 144 hours postdose on Day 1 to Day 21
measure: Part 1: Apparent Volume of Distribution (Vz/F) of S-309309
timeFrame: 0 (predose) up to 144 hours postdose on Day 1 to Day 21
measure: Part 1: Renal Clearance (CLR) of S-309309
timeFrame: 0 (predose) up to 144 hours postdose on Day 1 to Day 21
measure: Part 1: Fraction of Dose Excreted in Urine (Feu) of S-309309
timeFrame: 0 (predose) up to 144 hours postdose on Day 1 to Day 21
measure: 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
timeFrame: Baseline, Day 2, 5, 7 and 16
measure: Part 1: Change From Baseline of ECG Parameter: Heart Rate (HR)
timeFrame: Baseline, Day 2, 3, 4, 5, 6, 7 and 16
measure: Part 1: Placebo-Corrected Change From Baseline of ECG Parameters: QTcF, PR Interval, and QRS Duration
timeFrame: Baseline, Day 2, 5, 7 and 16
measure: Part 1: Placebo-Corrected Change From Baseline of ECG Parameter: HR
timeFrame: Baseline, Day 2, 3, 4, 5, 6, 7 and 16
measure: Part 1: Number of Participants With Categorical Outlier Values for HR, QTcF, PR, and QRS
timeFrame: Baseline up to Day 16
measure: Part 1: Number of Participants With Treatment-Emergent Changes for T-wave Morphology and Presence of U-wave
timeFrame: Baseline up to Day 16
measure: Part 2: Cmax of S-309309 and Midazolam
timeFrame: 0 (predose) up to 24 hours postdose on Day -2 to Day 16
measure: Part 2: Tmax of S-309309 and Midazolam
timeFrame: 0 (predose) up to 24 hours postdose on Day -2 to Day 16
measure: Part 2: AUC of S-309309 and Midazolam
timeFrame: 0 (predose) up to 24 hours postdose on Day -2 to Day 16
measure: Part 2: t1/2,z of S-309309 and Midazolam
timeFrame: 0 (predose) up to 24 hours postdose on Day -2 to Day 16
measure: Part 2: λz of S-309309 and Midazolam
timeFrame: 0 (predose) up to 24 hours postdose on Day -2 to Day 16
measure: Part 2: CL/F of S-309309 and Midazolam
timeFrame: 0 (predose) up to 24 hours postdose on Day -2 to Day 16
measure: Part 2: Vz/F of S-309309 and Midazolam
timeFrame: 0 (predose) up to 24 hours postdose on Day -2 to Day 16
measure: Part 2: MRT of Midazolam
timeFrame: 0 (predose) up to 24 hours postdose on Day -2 to Day 16
measure: Part 2: Number of Participants with TEAEs After Coadministration with Midazolam
timeFrame: Up to Day 28
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: ICON Early Phase Services, LLC
state: Texas
Study officials:
References: