Single Ascending Dose Safety Study of BMS-962476 in Healthy Subjects and Patients With Elevated Cholesterol on Statins

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01587365
First received: April 26, 2012
Last updated: September 2, 2013
Last verified: September 2013
  Purpose

To obtain safety and tolerability information in healthy subjects is administered as a single dose


Condition Intervention Phase
Atherosclerosis
Biological: BMS-962476
Biological: Placebo matching with BMS-962476
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Double-Blind, Placebo-Controlled, Ascending Single-Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-962476 in Healthy Subjects and in Patients With Hypercholesterolemia on Statin Therapy

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Safety and tolerability of BMS-962476 as measured by the number of subjects with serious adverse events, deaths or discontinuations due to adverse events (AEs), AEs of injection site reactions, or potentially clinically significant changes in vital signs [ Time Frame: Up to Day 43 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacodynamic effects of single subcutaneous (SC) and intravenous (IV) doses of BMS-962476 [ Time Frame: Up to Day 43 ] [ Designated as safety issue: No ]
    Pharmacodynamic effects will be measured by fasting lipid panel

  • Maximum observed plasma concentration (Cmax) of single dose pharmacokinetics (PK) and dose proportionality of BMS-962476 following SC and IV administration [ Time Frame: 17 time points up to Day 43 ] [ Designated as safety issue: No ]
  • Time of maximum observed plasma concentration (Tmax) of single dose pharmacokinetics (PK) and dose proportionality of BMS-962476 following SC and IV administration [ Time Frame: 17 time points up to Day 43 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time zero to the time of last quantifiable plasma concentration [AUC(0-T)] of single dose pharmacokinetics (PK) and dose proportionality of BMS-962476 following SC and IV administration [ Time Frame: 17 time points up to Day 43 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of single dose pharmacokinetics (PK) and dose proportionality of BMS-962476 following SC and IV administration [ Time Frame: 17 time points up to Day 43 ] [ Designated as safety issue: No ]
  • Plasma elimination half-life (T-HALF) of single dose pharmacokinetics (PK) and dose proportionality of BMS-962476 following SC and IV administration [ Time Frame: 17 time points up to Day 43 ] [ Designated as safety issue: No ]
  • Total body clearance (CL/F) of BMS-962476 SC Dosing [ Time Frame: 15 time points up to Day 43 ] [ Designated as safety issue: No ]
  • Total body clearance (CL) of BMS-962476 IV Dosing [ Time Frame: 17 time points up to Day 43 ] [ Designated as safety issue: No ]
  • Volume of distribution at steady state (Vss/F) of BMS-962476 SC Dosing [ Time Frame: 15 time points up to Day 43 ] [ Designated as safety issue: No ]
  • Volume of distribution at steady state (Vss) of BMS-962476 IV Dosing [ Time Frame: 15 time points up to Day 43 ] [ Designated as safety issue: No ]
  • Absolute bioavailability (F) of total and free BMS-962476 [ Time Frame: 15 time points up to Day 43 ] [ Designated as safety issue: No ]
  • Frequency of anti-BMS-962476 antibodies (immunogenicity) following single SC and IV doses of BMS-962476 [ Time Frame: Up to Day 43 ] [ Designated as safety issue: Yes ]

Enrollment: 66
Study Start Date: May 2012
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panel 1: BMS-962476 SC (0.01 mg/Kg) or Placebo
BMS-962476 0.01 mg/kg or Placebo matching with BMS-962476 0 mg liquid subcutaneously (SC), Single Dose, 1 day
Biological: BMS-962476 Biological: Placebo matching with BMS-962476
Experimental: Panel 2: BMS-962476 SC (0.03 mg/Kg) or Placebo
BMS-962476 0.03 mg/kg or Placebo matching with BMS-962476 0 mg liquid subcutaneously (SC), Single Dose, 1 day
Biological: BMS-962476 Biological: Placebo matching with BMS-962476
Experimental: Panel 3: BMS-962476 SC (0.1 mg/Kg) or Placebo
BMS-962476 0.1 mg/kg or Placebo matching with BMS-962476 0 mg liquid subcutaneously (SC), Single Dose, 1 day
Biological: BMS-962476 Biological: Placebo matching with BMS-962476
Experimental: Panel 4: BMS-962476 SC (0.3 mg/Kg) or Placebo
BMS-962476 0.3 mg/kg or Placebo matching with BMS-962476 0 mg liquid subcutaneously (SC), Single Dose, 1 day
Biological: BMS-962476 Biological: Placebo matching with BMS-962476
Experimental: Panel 5: BMS-962476 IV (0.3 mg/Kg) or Placebo
BMS-962476 0.3 mg/kg or Placebo matching with BMS-962476 0 mg liquid intravenously (IV), Single Dose, 1 day
Biological: BMS-962476 Biological: Placebo matching with BMS-962476
Experimental: Panel 6: BMS-962476 IV (1.0 mg/Kg) or Placebo
BMS-962476 1.0 mg/kg or Placebo matching with BMS-962476 0 mg liquid intravenously (IV), Single Dose, 1 day
Biological: BMS-962476 Biological: Placebo matching with BMS-962476
Experimental: Panel 7: Statin + BMS-962476 SC (0.1 mg/Kg) or Placebo
BMS-962476 0.1 mg/kg or Placebo matching with BMS-962476 0 mg liquid subcutaneously (SC), Single Dose, 1 day
Biological: BMS-962476 Biological: Placebo matching with BMS-962476
Experimental: Panel 8: Statin + BMS-962476 SC (0.3 mg/Kg) or Placebo
BMS-962476 0.3 mg/kg or Placebo matching with BMS-962476 0 mg liquid subcutaneously (SC), Single Dose, 1 day
Biological: BMS-962476 Biological: Placebo matching with BMS-962476

Detailed Description:
  • Study Classification: Pharmacokinetics and Pharmacodynamics
  • Intervention Model: Single Ascending Dose (SAD) study
  • Allocation: Randomized Non-Stratified
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy population

    • Untreated low density lipoprotein cholesterol (LDL-c) ≥ 130 and ≤ 190 mg/dL and triglycerides ≤ 200 mg/dL
    • Body Mass Index (BMI) of 18 to 35 kg/m2 inclusive
    • Men and women, ages 18 to 65 years, inclusive
  • Statin population

    • Patients with hypercholesterolemia on stable statin therapy for 6 weeks prior to enrollment
    • At enrollment, LDL-c ≥ 100mg/dL and triglycerides ≤ 200 mg/dL
    • Patients with controlled hypertension on a stable dose of no more than two antihypertensive drugs
    • BMI of 18 to 37 kg/m2 inclusive
    • Men and women, ages 18 to 75 years inclusive

Exclusion Criteria:

  • Healthy Population

    • Subjects with fasting LDL-c < 130 or > 190 mg/dL, or fasting triglycerides > 200 mg/dL
    • Subjects at increased 10-year cardiovascular risk of ≥ 20% based on Framingham risk score
    • Subjects with any significant acute or chronic medical illness at the time of screening, including history of cancer, known history of sickle cell disease or trait, and known history of thalassemia
  • Statin population

    • Patients with fasting LDL-c < 100mg/dL, or fasting triglycerides > 200 mg/dL on statin therapy
    • Patients on prescription or over the counter lipid-lowering therapy other than statin therapy
    • Patients with established atherosclerotic vascular disease
    • Patients with diabetes who are requiring oral or injectable anti-diabetic drug therapy
    • Patients with uncontrolled hypertension or controlled hypertension requiring more than two antihypertensive drugs
    • Patients with any significant acute or chronic medical illness that is severe, progressive or uncontrolled at the time of screening
  • Use of any lipid lowering medication including over the counter products (eg, niacin > 500 mg; omega-3 fatty acids > 1000 mg; red rice yeast; phytosterols or stanol esters) for lipid lowering within 30 days prior to screening visit (42 days for fibrates) with the exception of stable statin therapy in the target disease population
  • Prior treatment with any monoclonal antibody or investigational protein biologic within the preceding one year before study drug administration
  • Concurrent or use within 3 months of study drug administration of marketed or investigational systemic or inhaled corticosteroids or other immunosuppressant drugs, and within 6 weeks for topical corticosteroids
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01587365

Locations
United States, Ohio
Metabolic And Atherosclerosis Research Center/ Medpace Clinical Pharmacology
Cincinnati, Ohio, United States, 45227
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01587365     History of Changes
Other Study ID Numbers: CV206-001
Study First Received: April 26, 2012
Last Updated: September 2, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Atherosclerosis
Arteriosclerosis
Hypercholesterolemia
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014