A Study to Assess S-309309 in Healthy and Obese Participants
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 up to 3 groups. Healthy participants will be assigned to 1 of 2 ascending dose groups and will receive S-309309 or placebo in a fed state. Obese but otherwise healthy participants will be assigned to the high dose group or placebo. These participants will receive multiple oral administrations of S-309309 or placebo in a fed state.
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Part 1 and 2: Number of Participants with Treatment Emergent Adverse Events (TEAEs) [Up to Day 28]
Secondary Outcome Measures
- 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]
Eligibility Criteria
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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ICON Early Phase Services, LLC | San Antonio | Texas | United States | 78209 |
Sponsors and Collaborators
- Shionogi
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2018N1111