A Short and Long Intravenous Infusion Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of BMS-962212 in Healthy Subjects

A Randomized, Double-Blind, Placebo-Controlled, Ascending-Dose Short and Long Intravenous Infusion Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of BMS- 962212 in Healthy Subjects

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics following increasing doses of 2 h (Part A) and 5 day (Part B) continuous IV infusions of BMS-962212 in healthy subjects across the expected pharmacodynamic dose range.

Study Overview

• Status: Completed
• Conditions: Thrombosis
• Intervention / Treatment: Drug: BMS-962212; Drug: Aspirin; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 691
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • WCCT Global, LLC
    • Glendale, California, United States, 91206
      • California Clinical Trials Medical Group
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Parexel International - Baltimore Epcu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECG, and clinical laboratory determinations
• Body Mass Index (BMI) of 18 to 32 kg/m2 inclusive [as calculated by BMI = weight (kg)/ [height (m)]2
• This study permits the re-enrollment of a subject that has discontinued the study as a pre-treatment failure (ie, subject has not been randomized / has not been treated). If re-enrolled, the subject must be re-consented
• Men, ages 18 to 45 years, inclusive; women, ages 18-45, who are not of child-bearing potential
• Women must not be breastfeeding

Exclusion Criteria:

• Any significant acute or chronic medical illness
• Women of child-bearing potential
• Current or recent (within 3 months of study drug administration) gastrointestinal disease which by the judgment of the Investigator may increase a subject's risk of gastrointestinal bleeding (e.g., peptic or gastric ulcer disease, severe gastritis, history of gastrectomy)
• Any major surgery within 12 weeks of study drug administration
• History of blood transfusion, clinically significant bleeding event(s), or documented genetic bleeding diathesis or thrombophilia
• For Aspirin Containing Arm Participants Only: Known allergy to non-steroidal anti-inflammatory drugs or history of intolerance or abnormal sensitivity to aspirin (e.g gastrointestinal intolerance, bruising or bleeding, aspirin induced breathing difficulties or nasal polyps)

Other protocol defined inclusion/exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BMS-962212 Two Hour Administration; Intravenous administered over 2 hours of BMS-962212	Drug: BMS-962212; Intravenous Infusion administration over 2 hours or 5 days
Experimental: BMS-962212 5 Day Administration; Intravenous administered over 5 days of BMS-962212	Drug: BMS-962212; Intravenous Infusion administration over 2 hours or 5 days
Experimental: BMS-962212 and Aspirin; BMS-962212 intravenous administration, followed by aspirin oral administration, then combination administration of BMS-962212 and aspirin	Drug: BMS-962212; Intravenous Infusion administration over 2 hours or 5 days; Drug: Aspirin; Oral administration
Placebo Comparator: Placebo and Aspirin; Placebo intravenous administration, followed by aspirin, then combination administration of placebo and aspirin	Drug: Aspirin; Oral administration; Other: Placebo; Oral administration
Placebo Comparator: Placebo; Placebo intravenous administration	Other: Placebo; Oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AE)	measured by incidence	Up to 8 days
Serious Adverse Events (SAE)	measured by incidence	Up to 8 days
Discontinuation due to AE	measured by incidence	Up to 8 days
Death	measured by incidence	Up to 8 days
AE of clinically significant bleeding	measured by incidence	Up to 8 days
AE of clinically significant infusion reaction	measured by incidence	Up to 8 days
AE of clinically significant vital signs	measured by incidence	Up to 8 days
QTcF intervals - QT interval corrected for heart rate according to Fridericia's formula	measured by ECG	Up to 8 days
QRS - The interval from the beginning of the Q wave and the end of the S wave	measured by ECG	Up to 8 days
PR - The interval from the beginning of the P wave to the beginning of the QRS complex	measured by ECG	Up to 8 days
24-hour cardiac monitoring	measured by telemetry	Up to 6 days
Glomerular filtration rate (GFR)	measured by iohexol administration plasma clearance and the Chronic Kidney Disease-Epidemiology Collaborative Group (CKD EPI) equation	Up to 8 days
Cystatin-C	measured by serum biomarkers	Up to 8 days
Neutrophil gelatinase-associated lipocalin (NGAL)	measured by urine biomarkers	Up to 8 days
Monocyte chemoattractant protein-1 (MCP-1)	measured by urine biomarkers	Up to 8 days

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2013
• Primary Completion (Actual): February 2, 2016
• Study Completion (Actual): January 24, 2017

Study Registration Dates

• First Submitted: June 21, 2017
• First Submitted That Met QC Criteria: June 21, 2017
• First Posted (Actual): June 23, 2017

Study Record Updates

• Last Update Posted (Actual): July 2, 2017
• Last Update Submitted That Met QC Criteria: June 28, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: CV001-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No