Recruiting
Phase 1
First-in-Human Single and Multiple Dose of HL-400
Condition(s) studied
Parkinson Disease
Investigational drug(s) / intervention(s)
HL-400Placebo
HL-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.
Placebo: 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.
Study 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.
Eligibility
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.
Primary outcome measure(s)
- 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.
Trial sites (1)
| Facility | City | Region | Status |
|---|
| Pharmaron CPC, Inc. |
Baltimore |
Maryland |
Recruiting |
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