Summary
This is a randomized, double-blind, placebo-controlled, dose-escalation study in healthy subjects to evaluate the safety, tolerability, pharmacokinetics of HL-400 (a NLRP3 inhibitor) following oral single and multiple ascending dose administration.
Detailed Description
This is a randomized, double-blind, placebo-controlled, dose-escalation study in healthy subjects to evaluate the safety, tolerability, pharmacokinetics of HL-400 following oral single and multiple ascending dose administration.This study will consist of 3 parts, which are Part 1 (Single Ascending Dose), Part 2 (Multiple Ascending Dose) and Part3 (cerebrospinal fluid (CSF) Exposure).
Safety, pharmacokinetic parameters and relevant biomarkers will be assessed in the study.
Eligibility Criteria
Age Range: 18 years to 65 years
Inclusion Criteria:
* Are capable of giving written informed consent and complying with study procedures, schedule, requirements, and restrictions.
* Are between the ages of 18 and 65 years, inclusive, at screening.
* Female subjects have a negative serum hCG pregnancy test result at screening andDay （-1）, agree to refrain from ova donation for at least 3 months after the last dose, and willingness to comply with protocol-specified contraceptive methods.
* Male subjects with female partners of reproductive potential must agree to practice abstinence or to use a condom (male subject) plus an additional barrier method (female partner) of contraception for the duration of the study and for at least 3 months after last dosing; must also agree to refrain from sperm donation for at least 3 months after the last dose.
* Considered healthy by the Investigator, based on subject's reported medical history, full physical examination, clinical laboratory tests, 12-lead ECG, and vital signs.
* Non-smoker for at least 6 months prior to screening.
* Body mass index (BMI) of 18.0 to 32.0 kg/m2 inclusive, except for MAD Cohort 3 subjects with a BMI of of 32.0 to 42.0 kg/m2 inclusive.
Exclusion Criteria:
* Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity as determined by the Investigator.
* Pregnant (as determined by pregnancy test result) or breastfeeding women.
* History of chronic diarrhea, malabsorption, unexplained weight loss, food allergies or intolerance.
* Positive blood screen for human immunodeficiency virus (HIV 1/2), hepatitis B surface antigen (HBsAg), or hepatitis C antibody.
* A positive screen for alcohol or drugs of abuse at screening or Day -1.
* An unwillingness or inability to comply with food and beverage restrictions during study participation.
* Volunteers who have participated in any investigational drug or device study within past 3 months prior to dosing.
* Any condition or finding that in the Investigators opinion would put the subject or study conduct at risk if the subject were to participate in the study.