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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Thrombosis

Intervention / Treatment
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* Drug: BMS-962212
* Drug: Aspirin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 |