Safety Study of BMS-844421 for Treatment of Hypercholesterolemia

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

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).

Study Overview

• Status: Terminated
• Conditions: Atherosclerosis; Hypercholesterolemia
• Intervention / Treatment: Drug: BMS-844421; Drug: 0.9% sodium chloride injection solution

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: DOUBLE

Number of Arms

16

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm 1 - BMS-844421	Drug: BMS-844421; 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
PLACEBO_COMPARATOR: Arm 2 - 0.9% sodium chloride injection solution	Drug: 0.9% sodium chloride injection solution; Injection solution, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days
EXPERIMENTAL: Arm 3 - BMS-844421	Drug: BMS-844421; 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
PLACEBO_COMPARATOR: Arm 4 - 0.9% sodium chloride injection solution	Drug: 0.9% sodium chloride injection solution; Injection solution, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days
EXPERIMENTAL: Arm 5 - BMS-844421	Drug: BMS-844421; 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
PLACEBO_COMPARATOR: Arm 6 - 0.9% sodium chloride injection solution	Drug: 0.9% sodium chloride injection solution; Injection solution, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days
EXPERIMENTAL: Arm 7 - BMS-844421	Drug: BMS-844421; 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
PLACEBO_COMPARATOR: Arm 8 - 0.9% sodium chloride injection solution	Drug: 0.9% sodium chloride injection solution; Injection solution, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days
EXPERIMENTAL: Arm 9 - BMS-844421	Drug: BMS-844421; 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
PLACEBO_COMPARATOR: Arm 10 - 0.9% sodium chloride injection solution	Drug: 0.9% sodium chloride injection solution; Injection solution, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days
EXPERIMENTAL: Arm 11 - BMS-844421	Drug: BMS-844421; 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
PLACEBO_COMPARATOR: Arm 12 - 0.9% sodium chloride injection solution	Drug: 0.9% sodium chloride injection solution; Injection solution, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days
EXPERIMENTAL: Arm 13 - BMS-844421	Drug: BMS-844421; 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
PLACEBO_COMPARATOR: Arm 14 - 0.9% sodium chloride injection solution	Drug: 0.9% sodium chloride injection solution; Injection solution, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days
EXPERIMENTAL: Arm 15 - BMS-844421	Drug: BMS-844421; 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
PLACEBO_COMPARATOR: Arm 16 - 0.9% sodium chloride injection solution	Drug: 0.9% sodium chloride injection solution; Injection solution, Subcutaneous, 37.5 mg SAD: Once, 1 Day MAD: IV loading followed by 4 weekly doses, 29 Days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (ACTUAL): July 1, 2010
• Study Completion (ACTUAL): July 1, 2010

Study Registration Dates

• First Submitted: March 5, 2010
• First Submitted That Met QC Criteria: March 5, 2010
• First Posted (ESTIMATE): March 8, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): January 26, 2011
• Last Update Submitted That Met QC Criteria: January 25, 2011
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Atherosclerosis
• Other Study ID Numbers: CV198-002; 2009-012032-32 (EUDRACT_NUMBER)