Healthy Volunteers
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled, 2-part study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of SR1375 in healthy volunteers
Detailed description
This study is a phase 1,randomized, double-blind, placebo-controlled, 2-part study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of SR1375 in healthy volunteers. The study is divided into two parts, Part A (single ascending dose \[SAD\]) and Part B (multiple ascending dose \[MAD\]). In Part A, the scheduled dose cohorts include 1, 3, 10, 30, 100, and 200 mg; in Part B, the planned dose range will be 5, 15, and 50 mg.
Interventions
DRUGSR1375
The subject will be orally administered by single and multiple doses of SR1375 capsules with 240 ml water
DRUGMatching placebo
The subject will be orally administered by single and multiple doses of matching capsules with 240 ml water
Sponsors
Shanghai SIMR Biotechnology Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy volunteers will be included in the study if they satisfy all the following criteria: 1. Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects. 2. Adult males (for both SAD and MAD stage) and female (only for MAD stage), 18 to 55 years of age (inclusive) at screening. 3. Body mass index (BMI) ≥ 18 and ≤ 32 kg/m2, with a body weight ≥ 50 kg at screening. 4. Use of tobacco or nicotine-containing products: 5. Medically healthy without clinically significant abnormalities at the screening visit, at check-in on Day -1 and pre-dose on Day 1. 6. Conventional 12-lead ECG recording in triplicate (the mean of triplicate measurements will be used to determine eligibility at the screening visit, on Day -1 and pre-dose on Day 1) consistent with normal cardiac conduction and function. 7. Have suitable venous access for blood sampling. 8. Be willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
Exclusion criteria
Volunteers will be excluded from the study if there is evidence of any of the following: 1. History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or major surgery within the past three months determined by the Investigator to be clinically relevant. 2. Any history of malignant disease in the last 10 years (excluding completely treated cutaneous squamous cell or basal cell carcinoma). 3. Liver function test results (i.e., aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], and gamma glutamyl transferase \[GGT\]) and bilirubin (total, conjugated and unconjugated) elevated more than 1.5-fold above the upper limit of normal (ULN). 4. Positive test results for active human immunodeficiency virus (HIV-1 and HIV-2), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit. 5. Presence or having sequelae of gastrointestinal, liver (including Gilbert's syndrome), kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs. Exception: cholecystectomy is allowed. 6. History of substance abuse or alcohol abuse defined as \>21 units of alcohol per week for males and \>14 units of alcohol per week for females (for MAD cohorts only). One unit is equivalent to 8 g of alcohol: a half-pint (\ 285 mL) of beer, 1 glass (125 mL) of wine or 1 measure (25 mL) of spirits. 7. Is an employee of an Investigator or Sponsor or an immediate relative of an Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AE (Adverse Event) | Up to Day 32 | Incidence, type and severity and causality of AEs (including withdrawals due to safety or tolerability reasons) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma PK : Ctrough | Up to Day 32 | Plasma PK : Trough concentrations (Ctrough) (Part B only) |
| Plasma PK : AUC0-t | Up to Day 32 | Plasma PK : Area under the concentration-time curve from 0 to time of last quantifiable |
| Plasma PK : Tmax | Up to Day 32 | Plasma PK : Time to Cmax (Tmax) |
| Urine PK: Ae | Up to Day 4 | Urine PK: Cumulative amount of unchanged drug excreted in urine (Ae) |
| Urine PK: CLr | Up to Day 4 | Urine PK: Renal clearance (CLr) |
| Plasma PK : AUC0-∞ | Up to Day 32 | Plasma PK : Area under the concentration-time curve from t=0 to infinity (AUC0-∞) |
Countries
Australia
Outcome results
None listed