A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SAL0167 in Healthy Participants

Official title

A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of SAL0167 Tablets in Healthy Participants

Overview

This study aims to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of SAL0167 following single and multiple dose administration in healthy participants. The study consists of two parts (Part A and Part B) with 120 participants planned to be enrolled. Possible adjustments to sample size, treatment duration will depend upon emerging data.

Interventions

• Drug SAL0167 group
  Drug: SAL0167
• Drug SAL0167 placebo group
  Drug: SAL0167 placebo

Primary outcome measures

• Adverse events [Time frame: through study completion, an average of 50 days]

Eligibility criteria

Inclusion criteria

• Provide written informed consent before any study-specific procedure and be willing and able to comply with the requirements and restrictions specified in the informed consent form;
• Male or female, 18 to 65 years of age, inclusive;
• At screening, body weight ≥50 kg for males and ≥45 kg for females, and body mass index (BMI) 19.0 to 28.0 kg/m², inclusive (BMI = weight \[kg\]/height \[m\]²);
• At screening, no clinically significant findings on physical examination, vital signs, hematology, urinalysis, stool examination, serum chemistry, creatine kinase isoenzyme testing, coagulation tests, serology, or 12-lead ECG, as determined by the investigator; lipid parameters are excepted for Part B;
• For Part B, screening LDL-C ≥1.8 and ≤4.9 mmol/L and triglycerides (TG) ≤4.52 mmol/L;
• The participant and the participant's partner have no plans for pregnancy during the study or for 3 months after the last dose of investigational product; agree to use effective contraception (hormonal contraceptives are prohibited during the study) to prevent pregnancy; and agree not to donate sperm or ova/oocytes for reproductive or assisted-reproduction purposes.

Exclusion criteria

• Any clinically significant disease or medical history that, in the investigator's judgment, could interfere with study completion, including respiratory, cardiovascular, gastrointestinal, genitourinary, hematologic, endocrine, neurologic, psychiatric, malignant, or infectious disease; any disease or surgical history that could significantly alter drug absorption, metabolism, or elimination (e.g., gastrointestinal surgery, renal surgery, cholecystectomy, or another surgery considered likely to affect drug disposition); or habitual constipation or diarrhea;
• A history of a gastrointestinal disorder that, in the investigator's judgment, could affect food or drug absorption, such as recurrent vomiting, inflammatory bowel disease, chronic intestinal disease associated with malabsorption, Roemheld syndrome, or severe hernia;
• Severe cardiovascular or cerebrovascular disease within 12 months before screening, including decompensated heart failure, unstable angina, stroke or transient ischemic attack, acute myocardial infarction, or severe arrhythmia; a history of coronary artery bypass grafting or percutaneous coronary intervention; or planned cardiac stent placement or angioplasty during the study;
• A clinically significant acute drug or food allergic reaction within 2 weeks before screening; a history of allergy to two or more drugs, foods, or pollens; a history of allergic disease (e.g., asthma, urticaria, or eczematous dermatitis); or known or suspected allergy, hypersensitivity, or clinically significant reaction to SAL0167, a compound of the same class, placebo, or any excipient, as determined by the investigator;
• Use of any of the following foods, drugs, or treatments:

• Any prescription drug, nonprescription drug, Chinese herbal medicine, or dietary supplement (including vitamins or health supplements) within 2 weeks or 5 half-lives, whichever is longer, before screening;
• Current or previous treatment with inclisiran sodium or another investigational small interfering RNA (siRNA) PCSK9 inhibitor;
• Treatment with an approved or investigational PCSK9 inhibitor or a microsomal triglyceride transfer protein inhibitor (e.g., lomitapide) within 12 months before screening;
• Use of a drug or supplement that may affect cholesterol levels (e.g., a statin, ezetimibe, niacin, or omega-3 fatty acids) within 8 weeks before screening;
• Consumption of caffeine-containing (e.g., strong tea, coffee, or cola) or xanthine-rich (e.g., chocolate or cocoa) foods or beverages within 48 hours before the first dose, or unwillingness to abstain from these foods and beverages from 48 hours before the first dose through study completion;
• Receipt of a live vaccine, live-attenuated vaccine, or vaccine containing a live viral component within 3 months before screening, or planned receipt of such a vaccine during the study or within 1 month after study completion;
• Major trauma or major surgery (e.g., requiring general anesthesia) within 3 months before screening, or planned surgery during the study or within 3 months after study completion, except a procedure performed under local anesthesia;
• Participation in an interventional clinical study, including a study of an investigational drug or vaccine, another clinical study of SAL0167, or another cohort of this study, and receipt of investigational product within 3 months before screening;
• Blood donation (including apheresis) or blood loss ≥400 mL within 3 months before screening; blood donation or blood loss ≥200 mL, or receipt of a blood transfusion, within 1 month before screening; or planned donation of blood or blood components during the study or within 1 month after study completion;
• Difficulty with blood collection, inability to tolerate repeated venipuncture, or a clinically significant history of needle or blood phobia, as determined by the investigator;
• Difficulty swallowing or dietary requirements that preclude compliance with the standardized diet;
• Pregnant or breastfeeding female; positive pregnancy test in a female participant of childbearing potential; or unprotected sexual intercourse within 14 days before screening in a female participant of childbearing potential;
• Drug or substance abuse, excessive alcohol use, or heavy smoking, as evidenced by any of the following:

• History of drug or substance abuse, or a positive urine drug screen at screening;
• Average alcohol consumption of more than 14 units per week within 3 months before screening (1 unit is approximately 17.7 mL ethanol, equivalent to approximately 360 mL of 5% beer, 45 mL of 40% spirits, or 150 mL of 12% wine); a positive breath alcohol test at screening; or inability to abstain completely from alcohol-containing foods or beverages during the study;
• Average smoking of more than 5 cigarettes per day within 3 months before screening, or inability to abstain completely from tobacco products during the study;
• QTcF >450 ms for males or >470 ms for females;
• Positive test result for hepatitis B surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody, or Treponema pallidum-specific antibody;
• Poor anticipated compliance, as determined by the investigator, or any other factor that makes the participant unsuitable for the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Nanfang Hospital, Southern Medical University — Guangzhou

Identifiers

NCT: NCT07722299 · SAL0167A101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗