Evaluate Tolerability and Safety of HY209 in Healthy Volunteers

NCT06533878 | Enrolling By Invitation Phase 1

• 1 other identifier: HY209-Tab01
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Dementia

Outcome Measures

Primary Outcomes (1)

• 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.

Study Arms (10)

Part A Dose Level 1

OTHER

HY209 10 mg (1 tablet; 10 mg qd) fed, morning

Drug: HY-209

Part A Dose Level 2

OTHER

HY209 50 mg (1 tablet; 50 mg qd) fed, morning

Drug: HY-209

Part A Dose Level 3

OTHER

1. HY209 100 mg (1 tablet; 100 mg qd) fed, morning 2. HY209 100 mg (2 tablets; 50 mg bid) fed, morning, evening

Drug: HY-209

Part A Dose Level 4

OTHER

1. HY209 200 mg (2 tablets; 200 mg qd) fasting, morning 2. HY209 200 mg (2 tablets; 200 mg qd) fed, morning

Drug: HY-209

Part A Dose Level 5

OTHER

1. HY209 300 mg (3 tablets; 300 mg qd) fasting, morning 2. HY209 300 mg (3 tablets; 300 mg qd) fed, morning

Drug: HY-209

Part A Dose Level 6

OTHER

1. HY209 400 mg (4 tablets; 400 mg qd) fasting, morning 2. HY209 400 mg (4 tablets; 400 mg qd) fed, morning

Drug: HY-209

Part B Dose Level 1

PLACEBO COMPARATOR

1. HY209 150 mg (3 tablets; 50 mg tid) fed, morning, afternoon, evening 2. HY209 placebo fed, morning, afternoon, evening

Drug: HY-209; Drug: HY-209 placebo

Part B Dose Level 2

PLACEBO COMPARATOR

1. HY209 200 mg (2 tablets; 200 mg qd) fed, morning 2. HY209 placebo fed, morning

Drug: HY-209; Drug: HY-209 placebo

Part B Dose Level 3

PLACEBO COMPARATOR

1. HY209 200 mg (2 tablets; 100 mg bid) fed, morning, evening 2. HY209 placebo fed, morning, evening

Drug: HY-209; Drug: HY-209 placebo

Part B Dose Level 4

PLACEBO COMPARATOR

1. HY209 300 mg (3 tablets; 100 mg tid) fed, morning, afternoon, evening 2. HY209 placebo fed, morning, afternoon, evening

Drug: HY-209; Drug: HY-209 placebo

Interventions

HY-209 DRUG

Enteric coated tablet in the following colors: pink for 100 mg and yellow for 50 mg, and white for 10 mg

Part A Dose Level 1; Part A Dose Level 2; Part A Dose Level 3; Part A Dose Level 4; Part A Dose Level 5; Part A Dose Level 6; Part B Dose Level 1; Part B Dose Level 2; Part B Dose Level 3; Part B Dose Level 4

HY-209 placebo DRUG

Enteric coated tablet in the following colors: pink for 100 mg and yellow for 50 mg

Part B Dose Level 1; Part B Dose Level 2; Part B Dose Level 3; Part B Dose Level 4

Eligibility Criteria

• Age: 19 Years - 45 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects who have received a full explanation about the study and the characteristics of the investigational product (IP), understood them, and then have provided voluntary consent for the study participation and fulfillment of the subject obligations during the study
• Healthy adult males ≥ 19 years and ≤ 45 years of age at the time of screening
• Subjects with weight ≥ 55 kg and ≤ 90 kg and BMI ≥ 18.0 and \< 30.0 kg/m²
• Subjects without congenital or chronic diseases and pathological symptoms or findings in the medical examinations
• Subjects determined eligible for the study participation based on the results from laboratory tests, including serology, hematology, blood chemistry, urinalysis, and urine drug screening, vital signs, physical examinations, and electrocardiography (ECG), performed depending on the drug characteristics at screening (subjects with physical examinations, laboratory tests and ECG findings beyond the normal range may be allowed to take part in the study when they do not have clinically significant diseases and obvious ground for participation can be provided in the investigator's opinion)

You may not qualify if:

• Clinically significant diseases or past history that precludes the study participation in the investigator's opinion
• Occurrence of any diseases (illnesses) within 1 week prior to start of the IP dosing \[e.g., flu epidemic or common cold, fever ≥ 38℃\]). (However, when the disease is resolved in a short period of time, their study participation can be determined through a follow-up test after treatment.)
• Unable or unwilling to take tablets
• The following diseases and health conditions that may affect the pharmacokinetics (PK) of the IP, including absorption
• Gastrointestinal (GI) diseases (Crohn's disease, ulcer, acute or chronic pancreatitis, etc.)
• Past history of cholecystectomy, bariatric procedures and/or any GI surgery that may interfere with the PK profile of the study drug, except simple cholecystectomy or hernia surgery
• Rare hereditary problems of galactose intolerance, the Lapp lactose deficiency, or glucose galactose malabsorption
• The following laboratory test results at screening (However, for liver tests, any test results that are considered to be caused by clinically meaningless transient changes or one-time alcohol consumption and night-shift work and other lifestyle can be finally confirmed through follow-up tests after the correction)
• Elevated alanine aminotransferase (ALT) \> 1.1 x upper limit of normal (ULN)
• Elevated aspartate aminotransferase (AST) \> 1.2 x ULN
• Elevated total bilirubin \> 1.2 x ULN
• Elevated creatinine \> 0.1 mg/dL from the ULN
• Estimated glomerular filtration rate(eGFR) \< 60 mL/min/1.73 m²
• Systolic blood pressure (BP) ≥ 150 mmHg or ≤ 100 mmHg, or diastolic BP ≥ 100 mmHg or ≤ 60 mmHg in the vital signs as measured in a sitting position after taking a rest for at least 3 minutes
• Pulse rate \< 50 beats/min (bpm) or \> 90 bpm when measured in a sitting position after taking a rest for at least 3 minutes; or \< 45 bpm when (1) a normal thyroid function is confirmed with interview, physical examinations, and Thyroid stimulating Hormone(TSH) tests and (2) there is no clinical symptom of bradycardia (orthostatic hypotension and vertigo).

Sponsors & Collaborators

• Kukjeon Pharmaceutical Co.,Ltd.: lead

Study Sites (1)

Kukjeon Pharmaceutical Co., Ltd.

Anyang-si, Gyeonggi-do, South Korea

Location

Related Links

• Zhong M. TGR5 as a Therapeutic Target for Treating Obesity. Curr Top Med Chem \[Internet\] 2010 \[cited 2021 May 10\];10(4):386-96.
• Chang S, Kim YH, Kim YJ, Kim YW, Moon S, Lee YY, et al. Taurodeoxycholate increases the number of myeloid-derived suppressor cells that ameliorate sepsis in mice. Front Immunol \[Internet\] 2018 \[cited 2021 May 20\];9(SEP):1984.
• Kim H, Fang S. Crosstalk between FXR and TGR5 controls glucagon-like peptide 1 secretion to maintain glycemic homeostasis. Lab Anim Res \[Internet\] 2018 \[cited 2021 May 26\];34(4):140.
• Altman DG, Bland JM. Statistics notes. Treatment allocation in controlled trials: why randomise? BMJ \[Internet\] 1999 \[cited 2016 Aug 30\];318(7192):1209.
• Pai D, Woo J-M, Son MH, Lee C. The Reliability and Validity of the Korean Version of ColumbiaSuicide Severity Rating Scale in Alcohol Dependent Patients. J Korean Neuropsychiatr Assoc \[Internet\] 2015 \[cited 2019 Jun 21\];54(2):222-7.
• Svedlund J, Sjödin I, Dotevall G. GSRS--a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci \[Internet\] 1988 \[cited 2017 Jul 18\];33(2):129-34.
• Revicki DA, Wood M, Wiklund I, Crawley J. Reliability and validity of the Gastrointestinal Symptom Rating Scale in patients with gastroesophageal reflux disease. Qual Life Res \[Internet\] 1998 \[cited 2017 Jul 18\];7(1):75-83.
• Monés J, Adan A, Segú JL, López JS, Artés M, Guerrero T. Quality of life in functional dyspepsia. Dig Dis Sci \[Internet\] 2002 \[cited 2017 Jul 18\];47(1):20-6.
• Wiklund IK, Fullerton S, Hawkey CJ, Jones RH, Longstreth GF, Mayer EA, et al. An irritable bowel syndrome-specific symptom questionnaire: development and validation. Scand J Gastroenterol \[Internet\] 2003 \[cited 2017 Jul 18\];38(9):947-54.

MeSH Terms

Conditions

Dementia

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2024
• First Posted: August 1, 2024
• Study Start: September 13, 2023
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: August 15, 2024

Record last verified: 2024-07

Locations

KR (1)