Parkinson Disease
Conditions
Brief 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.
Interventions
DRUGHL-400
Part 1:Experimental: Single oral dose of HL-400, Single ascending doses, sequential assignment group design; Part 2: Experimental: Multiple oral doses of HL-400, Multiple ascending doses, QD for 14 days, sequential assignment group design; Part 3: Experimental: Multiple oral doses of HL-400, QD for 5 days.
DRUGPlacebo
Part 1: Placebo comparator: Single oral dose of placebo, single doses, matching placebo; Part 2: Placebo comparator: Multiple oral doses of placebo, multiple ascending doses, QD for 14 days, matching placebo.
Sponsors
Highlightll Pharmaceutical (USA) LLC
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and percentage of participants with adverse events (AEs) | From the time of taking first dose of study drug to 7 days after the last dose. | To evaluate the safety and tolerability of HL-400 following oral single and multiple ascending dose administration. |
| Number and percentage of adverse events (AEs) according to severity | From the time of taking first dose of study drug to 7 days after the last dose. | To evaluate the safety and tolerability of HL-400 following oral single and multiple ascending dose administration. |
| Change in 12-lead electrocardiogram (ECG) parameters (PR Interval, QRS Complex, QT Interval, QTC Interval) from baseline | From baseline to 7 days after the last dose. | To evaluate the safety and tolerability of HL-400 following oral single and multiple ascending dose administration. |
| Single Ascending Dose (SAD) Cohorts: Maximum observed plasma concentration (Cmax) of HL-400 | From 0.5 hour to 72 hours post-dose. | To characterize the PK in the plasma of HL-400 following oral single dose administration. |
| Single Ascending Dose (SAD) Cohorts: Time to reach maximum observed plasma concentration (Tmax) of HL-400 | From 0.5 hour to 72 hours post-dose. | To characterize the PK in the plasma of HL-400 following oral single dose administration. |
| Single Ascending Dose (SAD) Cohorts: Plasma decay half-life (t1/2) of HL-400 | From 0.5 hour to 72 hours post-dose. | To characterize the PK in the plasma of HL-400 following oral single dose administration. |
| Single Ascending Dose (SAD) Cohorts: Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUCinf) of HL-400 | From 0.5 hour to 72 hours post-dose. | To characterize the PK in the plasma of HL-400 following oral single dose administration. |
| Multiple Ascending Dose (MAD) Cohorts: Maximum observed plasma concentration (Cmax) of HL-400 | From Day 1 pre-dose to 72 hours after the last dose. | To characterize the PK in the plasma of HL-400 following oral multiple ascending dose administration. |
| Multiple Ascending Dose (MAD) Cohorts: Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUCinf) of HL-400 | From Day 1 pre-dose to 72 hours after the last dose. | To characterize the PK in the plasma of HL-400 following oral multiple ascending dose administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1.The cerebrospinal fluid (CSF) cohort: Maximum observed concentration (Cmax) of HL-400 in the CSF | From Day 1 pre-dose to 24 hours after the last dose | To characterize the PK in the CSF of HL-400 following oral multiple dose administration. |
| The cerebrospinal fluid (CSF) cohort: Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUCinf) of HL-400 in the CSF | From Day 1 pre-dose to 24 hours after the last dose | To characterize the PK in the CSF of HL-400 following oral multiple dose administration. |
Countries
United States
Outcome results
None listed