Safety, Tolerability, and Pharmacokinetics of ID119031166M With the Exploration of Pharmacodynamic Effects

Study Overview
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Brief Summary
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This study will evaluate safety, tolerability, and Pharmacokinetics (PK) of ID119031166M with the Exploration of Pharmacodynamic (PD) effects in Healthy Participants.

Detailed Description
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This is a Phase 1, randomized, double-blind, placebo-controlled, sequential single/repeated-dose study. This study is a dose-escalation study with healthy participants in single ascending dose (SAD) including food-effect and multiple ascending dose (MAD) cohorts to determine the highest allowable dose (HAD).

Official Title
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A Placebo-controlled, Randomized, Double-blind, Single and Multiple Dose-escalation Study to Evaluate Safety, Tolerability, and Pharmacokinetics of ID119031166M With the Exploration of Pharmacodynamic Effects in Healthy Participants

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: ID119031166M
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be Caucasian (White American of European or Latin American descent). Healthy participants of Japanese origin are allowed up to 50% in each MAD cohort. Body mass index (BMI) within the range of 18.5 to 30 kg/m^2 (inclusive) at the time of Screening. No congenital or chronic diseases that require treatment and without pathologic symptoms or signs on medical examinations. Participants with normal renal function. Women are eligible to participate if not pregnant, not breastfeeding. Male subjects should be willing to use 'highly effective' or 'applicable' contraceptive methods. Exclusion Criteria: Currently have an acute disease with active symptoms. History of melanoma or other skin issues (including, but not limited to pre-cancerous areas, atopic dermatitis, psoriasis, rosacea, excessive moles etc.). History of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, musculoskeletal, or cardiovascular disease and/or arrhythmias. History of clinically significant hypersensitivity reaction to any drugs or additives. History of any gastrointestinal disease. History of substance use disorder including history of drug abuse disorder or history of alcohol use disorder, or tobacco use disorder or excessive caffeine intake. Evidence of moderate or excessive alcohol consumption. Tested positive in viral serology tests (hepatitis B virus [HBV], hepatitis C virus [HCV], and human immunodeficiency virus [HIV]). Known family history or known presence of long QT syndrome. A history of hypokalemia. Use of concomitant medicines that prolong QT/QTc (QT Interval Corrected for Heart Rate). History of active viral hepatitis (hepatitis A, B, C, and E), or autoimmune hepatitis. History of Multiple Endocrine Neoplasia type 2. Solid organ transplantation, except corneal transplants. History or presence of neutropenia which is defined as absolute neutrophil count (ANC) < 1.5 at Screening and admission. Participants with a microalbuminuria. Hemoglobin levels below 12.0 g/dL at Screening or Baseline. White Blood Cell levels below 3.5 × 109/L at Screening or Baseline. Platelet count < 150,000/µL, international normalized ratio (INR) > 1.5, albumin < 3.5 g/dL

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAD: ID119031166M<br> | Drug: ID119031166M<br>* The participants will receive a single oral dose of ID119031166M or once daily oral doses of ID119031166M for 14 days.<br>|
| Experimental: MAD: ID119031166M<br> | Drug: ID119031166M<br>* The participants will receive a single oral dose of ID119031166M or once daily oral doses of ID119031166M for 14 days.<br>|
| Placebo Comparator: SAD: Placebo<br> | Drug: Placebo<br>* The participant will receive a oral dose of Placebo.<br>|
| Placebo Comparator: MAD: Placebo<br> | Drug: Placebo<br>* The participant will receive a oral dose of Placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Serious Adverse Events (SAEs) and Adverse Events (AEs) | To evaluate the safety and tolerability of single and multiple ascending doses of ID119031166M in healthy participants. | From Screening (Day -28 to -3) until termination (approximately Day 8 for SAD and Day 22 for MAD) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration determined directly from the concentration- time profile (Cmax) | To assess the PK of ID119031166M when given at single and multiple ascending doses in healthy participants. To explore food effect on PK of ID119031166M after a single-dose administration in healthy participants. | Day 1-4 for SAD and Day 1-17 for MAD | 
| Time of maximum plasma concentration determined directly from the concentration-time profile (Tmax) | To assess the PK of ID119031166M when given at single and multiple ascending doses in healthy participants. To explore food effect on PK of ID119031166M after a single-dose administration in healthy participants. | Day 1-4 for SAD and Day 1-17 for MAD | 
| Area under curve from pre-dose (time 0) to the time of the last quantifiable concentration (tlast) (AUC0-last) | To assess the PK of ID119031166M when given at single and multiple ascending doses in healthy participants. | Day 1-4 for SAD and Day 1-17 for MAD | 
| Dose-normalized Cmax | To assess the PK of ID119031166M when given at single and multiple ascending doses in healthy participants. | Day 1-4 for SAD and Day 1-17 for MAD | 
| Dose-normalized AUC from pre-dose (time 0) extrapolated to 24 hours (AUC0-24) | To assess the PK of ID119031166M when given at single and multiple ascending doses in healthy participants. | Day 1-4 for SAD and Day 1-17 for MAD | 
| Dose-normalized AUC0-last | To assess the PK of ID119031166M when given at single and multiple ascending doses in healthy participants. | Day 1-4 for SAD and Day 1-17 for MAD | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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First-in-human (FIH), Single ascending doses (SAD), Multiple ascending doses (MAD), Farnesoid X receptor (FXR) agonist, Noncirrhotic non-alcoholic steatohepatitis (NASH), Liver fibrosis