Evaluate Tolerability and Safety of HY209 in Healthy Volunteers
NCT Number: NCT06533878
Status: ENROLLING_BY_INVITATION
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Dementia
Interventions: DRUG: HY-209|DRUG: HY-209 placebo
Sponsor: Kukjeon Pharmaceutical Co.,Ltd.
Sex: MALE
Age: ADULT
Enrollment: 59
Study Design: Allocation: RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: SINGLE (OUTCOMES_ASSESSOR)|Primary Purpose: HEALTH_SERVICES_RESEARCH
Start Date: 2023-09-13
Completion Date: 2025-12-31
Locations: Kukjeon Pharmaceutical Co., Ltd., Anyang-Si, Gyeonggi-Do, Korea, Republic of

Summary:
* Primary study objectives in Parts A and B To determine the Maximum Tolerable Dose(MTD) of the study drug (repeated or single dose).
* Endpoint: • Adverse event(AEs), including objective and subjective symptoms, after the IP dosing as well as physical examinations, vital signs, ECGs, and laboratory tests findings related to the IP dosing

  • Dose-limiting toxicities (DLTs)
* Justification for endpoints: The safety will be assessed comprehensively by performing safety assessment and evaluating relevant variables by dose group.

The tolerability will be assessed in DLT analysis set. In a first-in-human clinical trial, tolerability of the drug administered is usually assessed through determination of dose-limiting toxicity (DLT). An accurate dose proportionality of toxicity was not observed, but toxicity was found at high doses, not at low doses following IV and oral administrations, except transdermal treatment. Thus, a relationship between toxicity and doses was confirmed.

In addition, HY209 showed a dose dependence in some efficacy endpoints, including dose-dependent inhibition of release of Tumor Necrosis Factor(TNF)-α and Il-1β, key inflammation factors related to inflammatory bowel disease. Thus, evaluating the occurrence of DLTs through sequential dose escalation is determined appropriate to assess the tolerability and safety of HY209.

* Primary study objectives in Part A (Dose levels 4-6): To evaluate the effects of food on HY209 bioavailability (absorption rate and volume) following a single oral dose in healthy volunteers.
* Endpoint: PK of HY209 at a fasting condition and after a high-fat meal Point estimates for the geometric mean ratio of variables (Area under concentration-time curve;AUC₀-₆, AUCₗₐₛₜ, AUC₀-∞, and Cmax) and the 90% confidence interval(CI) and Tmax .
* Justification for endpoints: For oral drugs, effects of food on bioavailability of the drugs are usually evaluated. Especially, a systemic exposure to bile acid drugs of enterohepatic circulation can be explained with a spillover from the liver to systemic circulatory system. Thus, a systemic exposure is thought to be affected by food, but the actual effects of food are triggered by combination of factors that affect in vivo elution of a drug and absorption of the active pharmaceutical ingredient(API) of the drug. As estimating the extent of effects on bioavailability is difficult without conducting an actual food effect study, there is a need for clinical evaluation.

Primary Outcome Measures: Adverse events, physical examinations, vital signs, ECGs, laboratory tests findings related to the IP dosing, Does limiting toxicity, PK assessment endpoints, Part A

* AEs, including objective and subjective symptoms, after the IP dosing as well as physical examinations, vital signs, ECGs, and laboratory tests findings related to the IP dosing
* \[Part A: Phase 1a or Phase 1 dose escalation\] incidence and frequency of DLTs observed until 7 days after HY209 treatment for each dose and dosage cohort
* \[Part A (Dose levels 4-6): effects of food on bioavailability\] point estimates of geometric mean ratio for PK parameters (AUC₀-₆, AUCₗₐₛₜ, AUC₀-∞, and Cmax) following a single dose at a fasting condition and after a high-fat meal and the 90% CI and Tmax

Part B

* AEs, including objective and subjective symptoms, after the IP dosing as well as physical examinations, vital signs, ECGs, and laboratory tests findings related to the IP dosing
* \[Part B: Phase 1b or Phase 1 cohort expansion\] incidence and frequency of DLTs observed until 7 days after the last dose of HY209 for each dose and dosage cohort, Test of DLTs observed until 7 days after the last does of HY209 for each dose and dosage cohort.