Non-alcoholic Steatohepatitis (NASH)
Conditions
Brief summary
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
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
Interventions
DRUGECC4703
ECC4703 will be administered as 1 mg, 10 mg and 40 mg capsules. ECC4703 will be administered as oral capsules during each dosing day.
DRUGPlacebo
Matching Placebo will be administered as oral capsules. Matching Placebo will be given orally during each dosing day.
Sponsors
Eccogene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events, with abnormal laboratory test results, abnormal ECGs, abnormal vital signs, and abnormal physical examinations | SAD: Up to 8 days and MAD: Up to 21 days | Safety Assessment evaluated through adverse events, laboratory evaluations, vital signs, ECGs, and physical examination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamic assessment: Glucose | MAD: Up to Day 21. | Measurement of Glucose |
| Pharmacodynamic assessment: Serum Insulin | MAD: Up to Day 21. | Measurement of Serum Insulin |
| Thyroid function assessment: FT4 | SAD: Up to Day 8 and MAD: Up to Day 21. | Measurement of Free Thyroxine |
| Thyroid function assessment: TT3 | SAD: Up to Day 8 and MAD: Up to Day 21. | Measurement of Total Triiodothyronine |
| Thyroid function assessment: FT3 | SAD: Up to Day 8 and MAD: Up to Day 21. | Measurement of Free Triiodothyronine |
| Thyroid function assessment: TT4 | SAD: Up to Day 8 and MAD: Up to Day 21. | Measurement of Total Thyroxine |
| Pharmacodynamic assessment: VLDL | MAD: Up to Day 21. | Measurement of Very Low Density Lipoprotein |
| Pharmacodynamic assessment: ApoB | SAD: Up to Day 8 and MAD: Up to Day 21. | Measurement of Apolipoprotein B |
| Pharmacokinetic Parameters: AUC0-24 | SAD: Up to Day 8 and MAD: Up to Day 21. | AUC from time 0 to 24 hour dosing interval |
| Pharmacokinetic Parameters: AUC0-tlast | SAD: Up to Day 8 | AUC from time 0 to the time of last quantifiable non-zero concentration |
| Pharmacokinetic Parameters: AUC0-tau | MAD: Up to Day 21. | AUC over a dosing interval from time 0 to time of last quantifiable concentration |
| Pharmacokinetic Parameters: AUC0-infinity | SAD: Up to Day 8 | AUC from time 0 extrapolated to infinity |
| Pharmacokinetic Parameters: Cmax | SAD: Up to Day 8 and MAD: Up to Day 21. | Maximum observed plasma concentration |
| Pharmacodynamic assessment: Lp(a) | MAD: Up to Day 21. | Measurement of Lipoprotein (a) |
| Pharmacokinetic Parameters: Ctau | MAD: Up to Day 21. | Observed concentration at the end of the dosing interval |
| Pharmacokinetic Parameters: tmax | SAD: Up to Day 8 and MAD: Up to Day 21. | Time of the maximum observed plasma concentration |
| Pharmacokinetic Parameters: tlag | SAD: Up to Day 8 and MAD: Up to Day 21. | Lag time (time delay between dosing and first observed plasma concentration) |
| Pharmacokinetic Parameters: t1/2 | SAD: Up to Day 8 and MAD: Up to Day 21. | Apparent terminal elimination half-life |
| Pharmacokinetic Parameters: Clast | SAD: Up to Day 8 | Last measurable non-zero concentration |
| Pharmacokinetic Parameters: tlast | SAD: Up to Day 8 | Time of last measurable non-zero concentration |
| Pharmacokinetic Parameters: CL/F | SAD: Up to Day 8 and MAD: Up to Day 21. | Apparent Clearance |
| Pharmacodynamic assessment: LDL-C | SAD: Up to Day 8 | Measurement of Low Density Lipoprotein Cholesterol |
| Pharmacodynamic assessment: HDL-C | MAD: Up to Day 21. | Measurement of High Density Lipoprotein Cholesterol |
| Pharmacodynamic assessment: TG | MAD: Up to Day 21. | Measurement of Triglycerides |
| Pharmacodynamic assessment: TC | MAD: Up to Day 21. | Measurement of Total Cholesterol |
| Pharmacodynamic assessment: LDL | MAD: Up to Day 21. | Measurement of Low Density Lipoprotein |
| Thyroid function assessment: TSH | SAD: Up to Day 8 and MAD: Up to Day 21. | Measurement of Thyroid Stimulating Hormone |
| Pharmacokinetic Parameters: C24 | SAD: Up to Day 8 and MAD: Up to Day 21. | Observed concentration at 24 hours post dose |
Countries
United States
Outcome results
None listed