Phase I Study to Assess Safety and Pharmacokinetics of GMI-1271 in Healthy Adult Subjects

Study Overview
=================
Brief Summary
-----------------
In this study, the investigators will evaluate the safety, pharmacokinetics and effect on target biomarkers of coagulation, cell adhesion, and leukocyte and platelet activation of GMI-1271, an E-selectin antagonist, in healthy volunteers.

Detailed Description
-----------------
Investigators will evaluate in a single ascending dose (SAD) and multiple ascending dose (MAD) fashion, the safety, pharmacokinetics and effect on target biomarkers of coagulation, cell adhesion, and leukocyte and platelet activation of GMI-1271, an E-selectin antagonist, in healthy volunteers.

Official Title
-----------------
A Randomized, Placebo Controlled, Phase1 Study to Assess the Safety and Pharmacokinetics of GMI-1271 in Healthy Adult Subjects

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: GMI-1271
* Drug: Placebo
* Drug: Enoxaparin Sodium (Lovenox®)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-75 years Male or female Medically healthy, as defined by the absence of clinically significant screening results (e.g. laboratory profile, medical history, electrocardiogram (ECG), physical examination) BMI 18-35 kg/m2 Voluntary consent to participate in the study No evidence of Lower Extremity Deep Vein Thrombosis (LE DVT) at baseline by ultrasound Exclusion Criteria: Use of any prescription, investigational, herbal, supplemental, or over the counter medications including aspirin within 14 days (for the SAD phase) and 7 days (for the MAD phase) prior to day 1 or unwilling/unable to refrain from the use of these medications on days 1-8 for the SAD phase and days 1-12 of the MAD phase of the study Previous administration of GMI-1271 Positive drug testing at screening and baseline or positive alcohol testing at baseline or unwilling/unable to refrain from the use of drugs or alcohol on days 1-8 for the SAD phase and days 1-12 for the MAD phase of the study Pregnant or breastfeeding Unwilling or unable to use contraception during the time of participation in the trial and 14 days afterwards (sexual abstinence is permissible) Positive HIV, Hepatitis B surface antigen or Hepatitis C antibody at screening Hypersensitivity or allergic reaction to compounds related to GMI-1271 Use of moderate caffeine (≥ 300 mg/day) within 48 hours prior to dosing (day 1) History of bleeding disorder Any liver function test > 1.5 times upper limit of normal or renal insufficiency with creatinine clearance < 30 ml/min.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GMI-1271<br>IV GMI-1271 | Drug: GMI-1271<br> <br> |
| Placebo Comparator: Placebo<br>IV Placebo | Drug: Placebo<br> <br> |
| Active Comparator: Enoxaparin Sodium (Lovenox®)<br>SC Lovenox® | Drug: Enoxaparin Sodium (Lovenox®)<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events as a measure of safety and tolerability | Adverse Event data review | 14-19 days | 
| Type of adverse events as a measure of safety and tolerability | Adverse Event data review | 14-19 days | 
| Severity of adverse events as a measure of safety and tolerability | Adverse Event data review | 14-19 days | 
| Review of lab results as a measure of Pharmacokinetics | Cmax (mg/mL) | 3-5 days | 
| Review of lab results as a measure of Pharmacokinetics | AUC (mg/mL) | 3-5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of bleeding | Adverse Event data review | 14-19 days |