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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
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SAD Cohorts 1 to 2: Participants receiving Placebo | Placebo Comparator | Participants in each SAD cohort will be randomized to receive placebo |
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| SAD Cohorts 1 to 2: Participants receiving ECC4703 | Experimental | 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). |
|
| MAD Cohorts 1 to 4: Participants receiving Placebo | Placebo Comparator | Participants will be randomized to receive a once-daily dose of placebo for 14 days. |
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| MAD Cohorts 1 to 4: Participants receiving ECC4703 | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ECC4703 | Drug | ECC4703 will be administered as 1 mg, 10 mg and 40 mg capsules. ECC4703 will be administered as oral capsules during each dosing day. |
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| 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 |
| 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 |
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Inclusion Criteria:
Additional Inclusion Criteria for Part 2 (MAD) Cohorts B2 to B4
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Eccogene | Eccogene Clinical Trials | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Eccogene Investigational Site | Las Vegas | Nevada | 89113 | United States |
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| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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Double-blind
| Placebo | Drug | Matching Placebo will be administered as oral capsules. Matching Placebo will be given orally during each dosing day. |
|
| 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. |