FTIH Study of ECC0509 in Healthy Volunteers

Study Overview
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Brief Summary
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A Phase 1, Single-Center, Randomized, Double-Blind, Placebo-Controlled, Single And Multiple Ascending Dose, First-Time-In-Human Study to Assess The Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ECC0509 in Healthy Volunteers.

Detailed Description
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This study will be conducted in up to seven cohorts of Single Ascending Dose (SAD) & 3 cohorts of Multiple Ascending Dose (MAD). SAD will consist of a staggered dosing approach with a dose range from 1mg to 80mg. Staggered dosing approach will not be deployed for MAD cohorts with a dose range of 8mg to 40mg. In the MAD cohort, the effect of food will also be assessed by comparing the PK profile of Day 10 fed conditions against Day 14 fasted conditions.

Official Title
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A Phase 1, Single-Center, Randomized, Double-Blind, Placebo-Controlled, Single And Multiple Ascending Dose, First-Time-In-Human Study To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Ecc0509 In Healthy Volunteers

Conditions
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Osteoarthritis, Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: Placebo
* Drug: ECC0509
* Drug: Placebo
* Drug: ECC0509


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Healthy male or non-childbearing potential female Age ≥18 and ≤65 years old BMI ≥18.0 and ≤32.0 kg/m2 Male participants agree to use contraception No clinically significant abnormal findings in physical examination, 12-lead electrocardiogram (ECG), laboratory tests, or medical history Able to understand and sign informed consent Key Exclusion Criteria: Significant allergic reactions to any drug. History of significant drug abuse or alcohol abuse within 1 year prior to screening Concomitant participation in any investigational study of any nature Use of any concomitant medication except for the occasional use of acetaminophen (up to 2 g daily) Donation of plasma within 7 days prior to dosing or donation or loss of 500 mL or more of whole blood within 8 weeks prior to dosing. Any clinically significant abnormal findings in the participant's physical examination, laboratory tests, pregnancy test, urine drug screen, alcohol breath test, or medical history which, in the opinion of the Investigator, would prevent the subject from participating in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: SAD Cohorts 1 to 7: Participants Receiving Placebo<br>Participants in each SAD cohort will be randomized to receive placebo. | Drug: Placebo<br>* Matching Placebo Placebo will be administered as oral capsules.<br>|
| Experimental: SAD Cohorts 1 to 7: Participants receiving ECC0509<br>Participants in each SAD cohort will be randomized to receive 1 of 7 escalating doses (1 mg, 4 mg, 10 mg, 20 mg, 40 mg, 60 mg, or 80 mg). | Drug: ECC0509<br>* ECC0509 1 mg and 10 mg capsules ECC0509 will be administered as oral capsules.<br>|
| Placebo Comparator: MAD Cohorts 1 to 3: Participants receiving Placebo<br>Participants will be randomized to receive a once-daily dose of placebo for 14 days. | Drug: Placebo<br>* Matching Placebo Placebo will be given orally during each dosing day.<br>|
| Experimental: MAD Cohorts 1 to 3: Participants receiving ECC0509<br>Participants will be randomized to receive a once-daily dose of 1 of 3 escalating doses (8 mg, 20 mg, or 40 mg) for 14 days. | Drug: ECC0509<br>* ECC0509 1 mg and 10 mg capsules Placebo will be given orally during each dosing day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events and serious adverse events | An adverse event is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Serious adverse event is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment. | SAD: Up to Day 8. MAD: Up to Day 21. | 
| Number of subjects with abnormal values for blood pressure | Systolic and diastolic blood pressure of subjects will be measured in a semi-supine position after at least 5 minutes of rest. | SAD: Up to Day 8. MAD: Up to Day 21. | 
| Number of subjects with abnormal values for pulse rate | Pulse rate of subjects will be measured in a semi-supine or supine position after at least 5 minutes of rest. | SAD: Up to Day 8. MAD: Up to Day 21. | 
| Number of subjects with abnormal values for respiratory rate | Respiratory rate of subjects will be measured in a semi-supine position after at least 5 minutes of rest. | SAD: Up to Day 8. MAD: Up to Day 21. | 
| Number of subjects with abnormal values for tympanic temperature | Tympanic temperature of subjects will be measured in a semi-supine position after at least 5 minutes of rest. | SAD: Up to Day 8. MAD: Up to Day 21. | 
| Number of subjects with abnormal values for electrocardiogram parameters | 12-lead electrocardiogram will be obtained using an electrocardiogram machine. | SAD: Up to Day 8. MAD: Up to Day 21. | 
| Number of subjects with abnormal findings for clinical chemistry parameters | Blood samples will be collected from subjects for analysis of clinical chemistry parameters including urea, potassium, AST, total bilirubin, direct bilirubin, creatinine sodium bicarbonate, chloride, ALT, albumin, glucose, calcium, phosphate, alkaline phosphatase, cholesterol. | SAD: Up to Day 8. MAD: Up to Day 21. | 
| Number of subjects with abnormal findings for hematology parameters | Blood samples will be collected from subjects for analysis of hematology parameters including platelet count, mean platelet volume, mean cell volume, mean cell hemoglobin, mean corpuscular hemoglobin concentration, white blood cells count, neutrophils, lymphocytes, monocytes, eosinophils, basophils, red blood cells count, hemoglobin and hematocrit. | SAD: Up to Day 8. MAD: Up to Day 21. | 
| Number of subjects with abnormal findings for coagulation parameters | Blood samples will be collected from subjects for analysis of coagulation parameters including Activated Thromboplastin Time, Prothrombin Time and International Normalized Ratio | SAD: Up to Day 8. MAD: Up to Day 21. | 
| Number of subjects with abnormal findings for urinalysis parameters | Urine samples will be collected from subjects for analysis of specific gravity, potential of hydrogen (pH) of urine, presence of glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, and leukocyte esterase in urine by dipstick test. Microscopic examination will be performed if blood or protein is abnormal. | SAD: Up to Day 8. MAD: Up to Day 21. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic assessment 1 | Area under the plasma concentration versus time curve (AUC) | SAD: Up to Day 8. MAD: Up to Day 21. | 
| Pharmacokinetic assessment 2 | Peak Plasma Concentration (Cmax) | SAD: Up to Day 8. MAD: Up to Day 21. | 
| Pharmacokinetic assessment 3 | Time of peak plasma concentration (Tmax) | SAD: Up to Day 8. MAD: Up to Day 21. | 
| Pharmacokinetic assessment 4 | Half life (T1/2) | SAD: Up to Day 8. MAD: Up to Day 21. | 
| Pharmacokinetic assessment 5 | Apparent total clearance after oral administration (Cl/F) | SAD: Up to Day 8. MAD: Up to Day 21. | 
| Pharmacokinetic assessment 6 | Apparent volume of distribution during terminal phase after oral administration (Vz/F) | SAD: Up to Day 8. MAD: Up to Day 21. | 
| Pharmacodynamic assessment | Plasma Semicarbazide-Sensitive Amine Oxidase (SSAO) Activity | SAD: Up to Day 8. MAD: Up to Day 21. |