FTIH of ECC4703 in Healthy Volunteers

Study Overview
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Brief Summary
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This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose and multiple ascending dose study of ECC4703 in healthy volunteers and participants with treatment unnecessary LDL-C under 160 mg/dL

Detailed Description
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This study will be conducted in two cohorts of Single Ascending Dose (SAD) with a dose range from 1mg to 400mg and in four cohorts of Multiple Ascending Dose (MAD) with a dose range of 40mg to 160mg to Investigate the Safety, Tolerability, PK, and PD of ECC4703 in Healthy Volunteers and Participants with Treatment Unnecessary LDL-C under 160 mg/dL

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Single and Repeated Dose Escalation, FTIH Study to Investigate the Safety, Tolerability, PK and PD of ECC4703 in Healthy Volunteers and Participants With Treatment-Unnecessary LDL-C Under 160 mg/dL

Conditions
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Non-alcoholic Steatohepatitis (NASH)

Intervention / Treatment
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* Drug: ECC4703
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female participants of any ethnic origin Age of 18 to 65 years BMI of 18.0 to 32.0 kg/m2 Female participants who are postmenopausal, confirmed by FSH test, or surgically sterile, confirmed by medical documentation, or if they are of child bearing potential agree to use at least 1 highly effective method of contraception and 1 additional effective method at the same time, or agree to practice true abstinence Male participants agree to use contraception, or agree to practice true abstinence No clinically significant findings in physical examination, 12-lead electrocardiogram (ECG), vital sign measurements, laboratory tests, or medical/psychiatric history Not taking any medication on a regular basis Able to understand and sign and date informed consent Additional Inclusion Criteria for Part 2 (MAD) Cohorts B2 to B4 Fasting LDL-C ≥ 100 mg/dL and ≤ 159 mg/dL at screening Not eligible for lipid-lowering therapy (such as statin) as decided by the qualified clinician at screening based on <2019 ACC/AHA Guidelines on the Primary Prevention of Cardiovascular Disease> Hemoglobin A1c (HbA1c) ≤ 6.5%. Exclusion Criteria: Females who are pregnant including a positive result of pregnancy test, planning to become pregnant, or breastfeeding. History of febrile illness or evidence of active infection within 14 days prior to the first dose of study; Use of any concomitant medication History of drug abuse or alcohol abuse within the past 5 years; Regular use of tobacco, nicotine or tobacco products within the past 6 months of the study ; Unwilling to abstain from alcohol containing products and/or xanthine/caffeine containing products, including any food and beverages, within 48 h prior to the first dose of study drug; Concomitant participation in any investigational study of any nature Blood loss of non-physiological reasons ≥ 200 ml (i.e. trauma, blood collection, blood donation) within 2 months prior to the first dose of study drug, or plan to donate blood during this trial and within 1 month after the last dosing; Abnormal renal function estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 Currently diagnosed type 2 diabetes mellitus (T2DM) or has history of T2DM. Significant allergic reaction to active ingredients or excipients of the study drug. Any clinically significant abnormal findings in the participant's physical examination, laboratory tests, pregnancy test, urine drug screen, alcohol test, or medical history which in the opinion of the Investigator would prevent the participants 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: SAD Cohorts 1 to 2: Participants receiving Placebo<br>Participants in each SAD cohort will be randomized to receive placebo | Drug: Placebo<br>* Matching Placebo will be administered as oral capsules. Matching Placebo will be given orally during each dosing day.<br>|
| Experimental: SAD Cohorts 1 to 2: Participants receiving ECC4703<br>Participants in each SAD cohort will be randomized to receive up to 4 escalating doses (1 mg, 4 mg, 12 mg, 32 mg, 80 mg, 160 mg, 320 mg or 400 mg). | Drug: ECC4703<br>* ECC4703 will be administered as 1 mg, 10 mg and 40 mg capsules. ECC4703 will be administered as oral capsules during each dosing day.<br>|
| Placebo Comparator: MAD Cohorts 1 to 4: Participants receiving Placebo<br>Participants will be randomized to receive a once-daily dose of placebo for 14 days. | Drug: Placebo<br>* Matching Placebo will be administered as oral capsules. Matching Placebo will be given orally during each dosing day.<br>|
| Experimental: MAD Cohorts 1 to 4: Participants receiving ECC4703<br>Participants will be randomized to receive a once-daily dose of 1 of 3 escalating doses (40 mg, 80 mg, or 160 mg) for 14 days. | Drug: ECC4703<br>* ECC4703 will be administered as 1 mg, 10 mg and 40 mg capsules. ECC4703 will be administered as oral capsules 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 participants with adverse events, with abnormal laboratory test results, abnormal ECGs, abnormal vital signs, and abnormal physical examinations | Safety Assessment evaluated through adverse events, laboratory evaluations, vital signs, ECGs, and physical examination. | SAD: Up to 8 days and MAD: Up to 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameters: AUC0-24 | AUC from time 0 to 24 hour dosing interval | SAD: Up to Day 8 and MAD: Up to Day 21. | 
| Pharmacokinetic Parameters: AUC0-tlast | AUC from time 0 to the time of last quantifiable non-zero concentration | SAD: Up to Day 8 | 
| Pharmacokinetic Parameters: AUC0-tau | AUC over a dosing interval from time 0 to time of last quantifiable concentration | MAD: Up to Day 21. | 
| Pharmacokinetic Parameters: AUC0-infinity | AUC from time 0 extrapolated to infinity | SAD: Up to Day 8 | 
| Pharmacokinetic Parameters: Cmax | Maximum observed plasma concentration | SAD: Up to Day 8 and MAD: Up to Day 21. | 
| Pharmacokinetic Parameters: C24 | Observed concentration at 24 hours post dose | SAD: Up to Day 8 and MAD: Up to Day 21. | 
| Pharmacokinetic Parameters: Ctau | Observed concentration at the end of the dosing interval | MAD: Up to Day 21. | 
| Pharmacokinetic Parameters: tmax | Time of the maximum observed plasma concentration | SAD: Up to Day 8 and MAD: Up to Day 21. | 
| Pharmacokinetic Parameters: tlag | Lag time (time delay between dosing and first observed plasma concentration) | SAD: Up to Day 8 and MAD: Up to Day 21. | 
| Pharmacokinetic Parameters: t1/2 | Apparent terminal elimination half-life | SAD: Up to Day 8 and MAD: Up to Day 21. | 
| Pharmacokinetic Parameters: Clast | Last measurable non-zero concentration | SAD: Up to Day 8 | 
| Pharmacokinetic Parameters: tlast | Time of last measurable non-zero concentration | SAD: Up to Day 8 | 
| Pharmacokinetic Parameters: CL/F | Apparent Clearance | SAD: Up to Day 8 and MAD: Up to Day 21. | 
| Pharmacodynamic assessment: LDL-C | Measurement of Low Density Lipoprotein Cholesterol | SAD: Up to Day 8 | 
| Pharmacodynamic assessment: HDL-C | Measurement of High Density Lipoprotein Cholesterol | MAD: Up to Day 21. | 
| Pharmacodynamic assessment: TG | Measurement of Triglycerides | MAD: Up to Day 21. | 
| Pharmacodynamic assessment: TC | Measurement of Total Cholesterol | MAD: Up to Day 21. | 
| Pharmacodynamic assessment: LDL | Measurement of Low Density Lipoprotein | MAD: Up to Day 21. | 
| Pharmacodynamic assessment: VLDL | Measurement of Very Low Density Lipoprotein | MAD: Up to Day 21. | 
| Pharmacodynamic assessment: ApoB | Measurement of Apolipoprotein B | SAD: Up to Day 8 and MAD: Up to Day 21. | 
| Pharmacodynamic assessment: Lp(a) | Measurement of Lipoprotein (a) | MAD: Up to Day 21. | 
| Pharmacodynamic assessment: Glucose | Measurement of Glucose | MAD: Up to Day 21. | 
| Pharmacodynamic assessment: Serum Insulin | Measurement of Serum Insulin | MAD: Up to Day 21. | 
| Thyroid function assessment: TT3 | Measurement of Total Triiodothyronine | SAD: Up to Day 8 and MAD: Up to Day 21. | 
| Thyroid function assessment: FT3 | Measurement of Free Triiodothyronine | SAD: Up to Day 8 and MAD: Up to Day 21. | 
| Thyroid function assessment: TT4 | Measurement of Total Thyroxine | SAD: Up to Day 8 and MAD: Up to Day 21. | 
| Thyroid function assessment: FT4 | Measurement of Free Thyroxine | SAD: Up to Day 8 and MAD: Up to Day 21. | 
| Thyroid function assessment: TSH | Measurement of Thyroid Stimulating Hormone | SAD: Up to Day 8 and MAD: Up to Day 21. |