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

NCT01587365 | Completed Phase 1

• 1 other identifier: CV206-001
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• 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

  Up to Day 43

Secondary Outcomes (12)

• Pharmacodynamic effects of single subcutaneous (SC) and intravenous (IV) doses of BMS-962476

  Up to Day 43

• Maximum observed plasma concentration (Cmax) of single dose pharmacokinetics (PK) and dose proportionality of BMS-962476 following SC and IV administration

  17 time points up to Day 43

• Time of maximum observed plasma concentration (Tmax) of single dose pharmacokinetics (PK) and dose proportionality of BMS-962476 following SC and IV administration

  17 time points up to Day 43

• 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

  17 time points up to Day 43

• 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

  17 time points up to Day 43

Study Arms (8)

Panel 1: BMS-962476 SC (0.01 mg/Kg) or Placebo

EXPERIMENTAL

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

Panel 2: BMS-962476 SC (0.03 mg/Kg) or Placebo

EXPERIMENTAL

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

Panel 3: BMS-962476 SC (0.1 mg/Kg) or Placebo

EXPERIMENTAL

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

Panel 4: BMS-962476 SC (0.3 mg/Kg) or Placebo

EXPERIMENTAL

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

Panel 5: BMS-962476 IV (0.3 mg/Kg) or Placebo

EXPERIMENTAL

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

Panel 6: BMS-962476 IV (1.0 mg/Kg) or Placebo

EXPERIMENTAL

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

Panel 7: Statin + BMS-962476 SC (0.1 mg/Kg) or Placebo

EXPERIMENTAL

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

Panel 8: Statin + BMS-962476 SC (0.3 mg/Kg) or Placebo

EXPERIMENTAL

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

Interventions

BMS-962476 BIOLOGICAL

Panel 1: BMS-962476 SC (0.01 mg/Kg) or Placebo; Panel 2: BMS-962476 SC (0.03 mg/Kg) or Placebo; Panel 3: BMS-962476 SC (0.1 mg/Kg) or Placebo; Panel 4: BMS-962476 SC (0.3 mg/Kg) or Placebo; Panel 5: BMS-962476 IV (0.3 mg/Kg) or Placebo; Panel 6: BMS-962476 IV (1.0 mg/Kg) or Placebo; Panel 7: Statin + BMS-962476 SC (0.1 mg/Kg) or Placebo; Panel 8: Statin + BMS-962476 SC (0.3 mg/Kg) or Placebo

Placebo matching with BMS-962476 BIOLOGICAL

Panel 1: BMS-962476 SC (0.01 mg/Kg) or Placebo; Panel 2: BMS-962476 SC (0.03 mg/Kg) or Placebo; Panel 3: BMS-962476 SC (0.1 mg/Kg) or Placebo; Panel 4: BMS-962476 SC (0.3 mg/Kg) or Placebo; Panel 5: BMS-962476 IV (0.3 mg/Kg) or Placebo; Panel 6: BMS-962476 IV (1.0 mg/Kg) or Placebo; Panel 7: Statin + BMS-962476 SC (0.1 mg/Kg) or Placebo; Panel 8: Statin + BMS-962476 SC (0.3 mg/Kg) or Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (1)

Metabolic And Atherosclerosis Research Center/ Medpace Clinical Pharmacology

Cincinnati, Ohio, 45227, United States

Location

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Atherosclerosis

Interventions

BMS-962476

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2012
• First Posted: April 30, 2012
• Study Start: May 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: September 4, 2013

Record last verified: 2013-09

Locations

US (1)