Safety Study of BMS-844421 for Treatment of Hypercholesterolemia

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability, serum concentrations and pharmacodynamic effects on serum low-density lipoprotein (LDL) cholesterol of single and multiple subcutaneous and intravenous doses of BMS-844421 in healthy subjects (SAD) and in subjects with elevated cholesterol (MAD).

Official Title
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Randomized, Double-blind, Placebo-Controlled, Ascending Single- and Multiple-Dose Study to Evaluate the Safety , Pharmacokinetics and Pharmacodynamics of BMS-844421 in Healthy Subjects and in Subjects With Elevated Cholesterol

Conditions
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Atherosclerosis, Hypercholesterolemia

Intervention / Treatment
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* Drug: BMS-844421
* Drug: 0.9% sodium chloride injection solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Subjects (SAD) Healthy Subjects (MAD) with untreated elevated cholesterol Body Mass Index (BMI) of 18 to 30 kg/m² inclusive Women who are not of childbearing potential and men, ages 18 to 45 Exclusion Criteria: Any significant acute or chronic medical illness History of liver or renal disorders Prior use of any prescription or over-the-counter lipid lowering drugs, within 8 weeks prior to study drug administration

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1 - BMS-844421<br> | Drug: BMS-844421<br>* Ready-to-use stock solution for SC and IV, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days<br>|
| Placebo Comparator: Arm 2 - 0.9% sodium chloride injection solution<br> | Drug: 0.9% sodium chloride injection solution<br>* Injection solution, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days<br>|
| Experimental: Arm 3 - BMS-844421<br> | Drug: BMS-844421<br>* Ready-to-use stock solution for SC and IV, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days<br>|
| Placebo Comparator: Arm 4 - 0.9% sodium chloride injection solution<br> | Drug: 0.9% sodium chloride injection solution<br>* Injection solution, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days<br>|
| Experimental: Arm 5 - BMS-844421<br> | Drug: BMS-844421<br>* Ready-to-use stock solution for SC and IV, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days<br>|
| Placebo Comparator: Arm 6 - 0.9% sodium chloride injection solution<br> | Drug: 0.9% sodium chloride injection solution<br>* Injection solution, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days<br>|
| Experimental: Arm 7 - BMS-844421<br> | Drug: BMS-844421<br>* Ready-to-use stock solution for SC and IV, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days<br>|
| Placebo Comparator: Arm 8 - 0.9% sodium chloride injection solution<br> | Drug: 0.9% sodium chloride injection solution<br>* Injection solution, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days<br>|
| Experimental: Arm 9 - BMS-844421<br> | Drug: BMS-844421<br>* Ready-to-use stock solution for SC and IV, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days<br>|
| Placebo Comparator: Arm 10 - 0.9% sodium chloride injection solution<br> | Drug: 0.9% sodium chloride injection solution<br>* Injection solution, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days<br>|
| Experimental: Arm 11 - BMS-844421<br> | Drug: BMS-844421<br>* Ready-to-use stock solution for SC and IV, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days<br>|
| Placebo Comparator: Arm 12 - 0.9% sodium chloride injection solution<br> | Drug: 0.9% sodium chloride injection solution<br>* Injection solution, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days<br>|
| Experimental: Arm 13 - BMS-844421<br> | Drug: BMS-844421<br>* Ready-to-use stock solution for SC and IV, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days<br>|
| Placebo Comparator: Arm 14 - 0.9% sodium chloride injection solution<br> | Drug: 0.9% sodium chloride injection solution<br>* Injection solution, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days<br>|
| Experimental: Arm 15 - BMS-844421<br> | Drug: BMS-844421<br>* Ready-to-use stock solution for SC and IV, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days<br>|
| Placebo Comparator: Arm 16 - 0.9% sodium chloride injection solution<br> | Drug: 0.9% sodium chloride injection solution<br>* Injection solution, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To asses safety, tolerability, pharmacodynamic effects of BMS-844421 on PCSK9 concentrations |  | At the conclusion of the MAD part of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess single and multiple dose pharmacokinetics of BMS-844421 |  | All outcomes will be assessed at the conclusion of the MAD part of the study | 
| Assess the absolute bioavailability of single BMS-844421 SC doses |  | All outcomes will be assessed at the conclusion of the MAD part of the study | 
| Assess the effects of multiple doses of BMS-844421on lipid components |  | All outcomes will be assessed at the conclusion of the MAD part of the study |