Clinical trial NCT06997484: First-in-Human Single and Multiple Dose of HL-400
Official title: A Randomized, Double-blind, Placebo-controlled, Sequential Parallel Group, Single and Multiple Ascending Dose (SAD/MAD) Study in Healthy Subjects to Evaluate the Safety, Tolerability, Pharmacokinetics of HL-400 Following Oral Administration
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Parkinson Disease
Lead sponsor: Highlightll Pharmaceutical (USA) LLC
Sponsor class: INDUSTRY
First posted: 2025-05-30
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 and body weight not less than 50 kg.

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 outcomes:
measure: Number and percentage of participants with adverse events (AEs)
timeFrame: From the time of taking first dose of study drug to 7 days after the last dose.
measure: Number and percentage of adverse events (AEs) according to severity
timeFrame: From the time of taking first dose of study drug to 7 days after the last dose.
measure: Change in 12-lead electrocardiogram (ECG) parameters (PR Interval, QRS Complex, QT Interval, QTC Interval) from baseline
timeFrame: From baseline to 7 days after the last dose.
measure: Single Ascending Dose (SAD) Cohorts: Maximum observed plasma concentration (Cmax) of HL-400
timeFrame: From 0.5 hour to 72 hours post-dose.
measure: Single Ascending Dose (SAD) Cohorts: Time to reach maximum observed plasma concentration (Tmax) of HL-400
timeFrame: From 0.5 hour to 72 hours post-dose.
measure: Single Ascending Dose (SAD) Cohorts: Plasma decay half-life (t1/2) of HL-400
timeFrame: From 0.5 hour to 72 hours post-dose.
measure: Single Ascending Dose (SAD) Cohorts: Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUCinf) of HL-400
timeFrame: From 0.5 hour to 72 hours post-dose.
measure: Multiple Ascending Dose (MAD) Cohorts: Maximum observed plasma concentration (Cmax) of HL-400
timeFrame: From Day 1 pre-dose to 72 hours after the last dose.
measure: Multiple Ascending Dose (MAD) Cohorts: Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUCinf) of HL-400
timeFrame: From Day 1 pre-dose to 72 hours after the last dose.
Secondary outcomes:
measure: 1.The cerebrospinal fluid (CSF) cohort: Maximum observed concentration (Cmax) of HL-400 in the CSF
timeFrame: From Day 1 pre-dose to 24 hours after the last dose
measure: 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
timeFrame: From Day 1 pre-dose to 24 hours after the last dose
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Pharmaron CPC, Inc.
state: Maryland
Study officials:
References: