A 2-Part, Phase 1, Single and Multiple Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of CAT-2054 in Healthy Subjects

Study Overview
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Brief Summary
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This is a 2-part, Phase 1, placebo-controlled, double-blind, randomized, single and multiple ascending dose study. CAT-2054 will be administered either as an uncoated capsule (CAT-2054) or a coated capsule (CAT-2054-C). In Part A, CAT-2054 or placebo is administered as a single dose in a fasting state at 4 dose levels; at 3 dose levels, subjects will return for a second dose of the study drug after a high-fat meal. Additionally, at 1 dose level, CAT-2054-C or placebo will be administered as a single dose in a fasting state, and subjects will return for a second dose of the study drug after a high-fat meal. In Part B, CAT-2054 will be administered as multiple ascending doses at 4 dose levels for 14 consecutive days. In selected cohorts, CAT-2054, CAT-2054-C or CAT-2054 with atorvastatin will be dosed to assess safety in anticipation of future clinical trials.

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: CAT-2054
* Drug: Placebo
* Drug: CAT-2054-C
* Drug: Atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written informed consent before any study-specific procedure Good health as determined by medical history, physical examination, vital sign measurements, ECG, and clinical laboratory measurements Satisfies one of the following: Females not of childbearing potential: non-pregnant and non-lactating surgically sterile or postmenopausal 2 years or less with a follicle-stimulating hormone assessment greater than or equal to 40 IU/L Males: surgically sterile, abstinent, or subject or partner is utilizing an acceptable contraceptive method during and 3 months after the last study dose For Part B only, measured at Screening: Fasting LDL-C ≥100 mg/dL; or (Cohort B6 only) fasting LDL-C ≥130 mg/dL Body mass index (BMI) between 18 and 30 kg/m², inclusive, for Part A and between 18 and 40 kg/m², inclusive, for Part B, and body weight >50 kg at Screening Exclusion Criteria: Use of prescription drugs or non-prescription drugs including herbals, and dietary supplements (including multivitamins and any product containing niacin or omega-3 fatty acids above the Recommended Daily Allowance) within 2 weeks before dosing. Additionally for Part B only, use of any lipid-regulating prescription drug, non-prescription drug, herbal, or dietary supplement within 6 weeks before dosing Clinically significant disease that requires a physician's care and/or would interfere with study evaluations Clinically significant electrocardiogram (ECG) abnormalities or laboratory results as assessed by the investigator, such as QTcF >450 Use of any investigational drug or participation in any investigational study within 30 days prior to screening or 5 half-lives of the study agent, whichever is longer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A1, Dose Level 1: CAT-2054 or placebo fasting<br>Single dose | Drug: CAT-2054<br> <br> Drug: Placebo<br> <br> |
| Experimental: Cohort A2, Dose Level 2: CAT-2054 or placebo fasting and fed<br>Single dose | Drug: CAT-2054<br> <br> Drug: Placebo<br> <br> |
| Experimental: Cohort A3, Dose Level 3: CAT-2054 or placebo fasting and fed<br>Single dose | Drug: CAT-2054<br> <br> Drug: Placebo<br> <br> |
| Experimental: Cohort A4, Dose Level 4: CAT-2054 or placebo fasting and fed<br>Single dose | Drug: CAT-2054<br> <br> Drug: Placebo<br> <br> |
| Experimental: Cohort A5, Dose Level 5: CAT-2054-C or placebo fasting and fed<br>Single dose | Drug: Placebo<br> <br> Drug: CAT-2054-C<br> <br> |
| Experimental: Cohort B1, Dose Level 1: CAT-2054 or placebo<br>Multiple dose for 14 days | Drug: CAT-2054<br> <br> Drug: Placebo<br> <br> |
| Experimental: Cohort B2, Dose Level 2: CAT-2054 or placebo<br>Multiple dose for 14 days | Drug: CAT-2054<br> <br> Drug: Placebo<br> <br> |
| Experimental: Cohort B3, Dose Level 3: CAT-2054 or placebo<br>Multiple dose for 14 days | Drug: CAT-2054<br> <br> Drug: Placebo<br> <br> |
| Experimental: Cohort B4, Dose Level 4: CAT-2054 or placebo<br>Multiple dose for 14 days | Drug: CAT-2054<br> <br> Drug: Placebo<br> <br> |
| Experimental: Cohort B5, Dose Level 5: CAT-2054 or placebo<br>Multiple dose for 14 days | Drug: CAT-2054<br> <br> Drug: Placebo<br> <br> |
| Experimental: Cohort B6, Dose Level 6: CAT-2054 with atorvastatin<br>Multiple dose for 14 days | Drug: CAT-2054<br> <br> Drug: Atorvastatin<br> <br> |
| Experimental: Cohort B7, Dose Level 7: CAT-2054 or placebo<br>Multiple dose for 14 days | Drug: CAT-2054<br> <br> Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of adverse events |  | up to 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCinf of CAT-2054 |  | Days 1 through 4 | 
| Cmax of CAT-2054 |  | up to 3 weeks | 
| Changes from baseline for hematology, chemistry, coagulation and urinalysis |  | up to 3 weeks | 
| Assess the pharmacodynamic effects of multiple doses of CAT-2054 on serum lipids LDL-C, non-HDL-C, total cholesterol, triglycerides, HDL-C, apoB, and PCSK9. |  | up to 3 weeks | 
| AUC48 of Atorvastatin |  | up to 3 weeks |