This is a single-centre, randomized, double-blind, placebo-controlled Phase 1 study to assess safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of HL40626S tablets following single and multiple ascending oral doses to healthy adult participants aged 18-55 years.
Inclusion Criteria:
Exclusion Criteria:
Clinically significant abnormal medical history, such as gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, drug hypersensitivity, as determined by the Investigator, any abnormal findings on physical examination, VS measurements, ECG or laboratory tests at Screening, Admission or pre dose on Day 1 that, in the opinion of the Investigator, could jeopardize achieving the study objectives and/or compromise the participant's safety.
Any of the following ECG findings at Screening, Admission and/or pre dose on Day 1:
Resting HR < 40 bpm or >100 bpm when vital signs are measured at Screening
SARS-CoV-2 positive by PCR at Admission regardless of symptoms.
Unstable cardiovascular disease, including recent (within 6 months of screening) myocardial infarction or cardiac arrhythmia.
Ongoing liver disease or unexplained liver function test (LFT) elevations, defined as ALT, AST, gamma glutamyltransferase (GGT), alkaline phosphatase (ALP) or total/direct bilirubin > upper limit of the reference range (ULRR) at Screening or Admission. Participants with confirmed Gilbert's syndrome will not be permitted to enroll in the study.
Indications of pre-metabolic syndrome and/or systemic inflammation, as suggested by high-sensitivity C-reactive protein (hsCRP) of > 3 mg/L, elevated erythrocyte sedimentation rate (Male ≥ 15 mm/hr, Female ≥ 20 mm/hr) or Hemoglobin A1c (HbA1c) >5.3% at Screening.
History of cancer (malignancy) with the exception of basal or squamous cell carcinoma of the skin.
Respiratory tract infection (upper and/or lower) treated with antibiotics within 12 weeks of Screening.
Clinically significant infection or known inflammatory condition or history of clinically significant infection within 28 days prior to study drug administration on Day 1 that, in the opinion of the Investigator, would affect the participant's ability to participate in the trial.
History of drug or alcohol abuse (as defined by DSM-V) within 12 months prior to Screening.
Positive test result for alcohol (breath) or drugs of abuse (urine) at Screening or Admission.
Positive serology result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab) or human immunodeficiency virus antibody (HIV Ab) at Screening.
Active or recent herpes simplex or herpes zoster infection, if considered clinically relevant as per investigator discretion.
Venous access considered inadequate for PK sample collection; history of evidence of adverse symptoms associated with phlebotomy or blood donation.
Participation in a study of any investigational drug, device, biologic or other agent within 30 days (or 5 half-lives, whichever is longer [as applicable]) prior to Day 1.
Loss or donation of blood >500 mL (within 30 days prior to Screening); donation of bone marrow or peripheral stem cells (within 90 days prior to Day 1); or donation of plasma (within 7 days prior to Screening).
No more than 10 standard drinks per week per NHMRC alcohol guidelines within 90 days prior to screening.
Use of alcohol within 72 hours prior to study drug administration on Day 1.
Use of prescription drugs within 14 days (or 5 half-lives, whichever is longer), or non-prescription drugs and/or herbal supplements within 7 days (or 5 half-lives, whichever is longer) prior to study drug administration on Day 1. Exception: hormonal contraceptives, acetaminophen ≤ 1 gram/day or ibuprofen ≤ 800 mg/day may be administered at Investigator's discretion.
a.joseph@nucleusnetwork.com.au
The study will be double-blinded. The participants and the clinical personnel involved in the collection, monitoring, revision, or evaluation of AEs, or personnel who could have an impact on the outcome of the study will be blinded with respect to the participant's treatment assignment (HL40626S or placebo).
Healthy participants receive single fasting oral HL40626S tablets in five sequential dose-escalation cohorts. Sentinel safety evaluation is required before full cohort dosing.
Healthy participants receive single fasting oral placebo tablets matching HL40626S, one dose per participant.
Healthy participants receive once-daily fasting oral HL40626S tablets for 14 consecutive days across three sequential cohorts.
Healthy participants receive once-daily oral matching placebo tablets for 14 days.
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