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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

April 26, 2012
September 2, 2013
May 2012
May 2013   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01587365 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Single Ascending Dose Safety Study of BMS-962476 in Healthy Subjects and Patients With Elevated Cholesterol on Statins
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

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

  • Study Classification: Pharmacokinetics and Pharmacodynamics
  • Intervention Model: Single Ascending Dose (SAD) study
  • Allocation: Randomized Non-Stratified
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Atherosclerosis
  • Biological: BMS-962476
  • Biological: Placebo matching with BMS-962476
  • 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
    Interventions:
    • 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
    Interventions:
    • 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
    Interventions:
    • 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
    Interventions:
    • 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
    Interventions:
    • 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
    Interventions:
    • 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
    Interventions:
    • 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
    Interventions:
    • Biological: BMS-962476
    • Biological: Placebo matching with BMS-962476
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
66
May 2013
May 2013   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01587365
CV206-001
No
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP