Safety Study of BMS-844421 for Treatment of Hypercholesterolemia

• ClinicalTrials.gov Identifier: NCT01082562
• Recruitment Status: Terminated
• First Posted: March 8, 2010
• Last Update Posted: January 26, 2011
• Sponsor: Bristol-Myers Squibb
• Information provided by: Bristol-Myers Squibb

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Atherosclerosis; Hypercholesterolemia	Drug: BMS-844421; Drug: 0.9% sodium chloride injection solution	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: April 2010
• Actual Primary Completion Date: July 2010
• Actual Study Completion Date: July 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. To asses safety, tolerability, pharmacodynamic effects of BMS-844421 on PCSK9 concentrations [ Time Frame: At the conclusion of the MAD part of the study ]

Secondary Outcome Measures :

1. Assess single and multiple dose pharmacokinetics of BMS-844421 [ Time Frame: All outcomes will be assessed at the conclusion of the MAD part of the study ]
2. Assess the absolute bioavailability of single BMS-844421 SC doses [ Time Frame: All outcomes will be assessed at the conclusion of the MAD part of the study ]
3. Assess the effects of multiple doses of BMS-844421on lipid components [ Time Frame: All outcomes will be assessed at the conclusion of the MAD part of the study ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

Germany

Local Institution

Berlin, Germany, 14050

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

More Information

• Responsible Party: Study Director, Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT01082562
• Other Study ID Numbers: CV198-002; 2009-012032-32 ( EudraCT Number )
• First Posted: March 8, 2010
• Last Update Posted: January 26, 2011
• Last Verified: January 2011

Additional relevant MeSH terms:

Atherosclerosis; Hypercholesterolemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases