Placebo-controlled Single Dose Study to Evaluate Safety and Pharmacokinetics of GMI-1271 in Healthy Volunteers

A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Intravenous Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GMI-1271 in Healthy Adult Subjects

The purpose of this study is to evaluate safety, tolerability and pharmacokinetics of single ascending IV doses of GMI-1271 in healthy adult subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Adult Subjects
• Intervention / Treatment: Drug: Placebo; Drug: GMI-1271

Detailed Description

This is a randomized, double-blind, placebo-controlled, single ascending IV dose study conducted at one study center in the United States (US). One (1) cohort of 12 subjects (6 active and 6 placebo) and two (2) cohorts of 8 subjects (6 active and 2 placebo) are planned for evaluation. Subjects will participate in only one cohort. Safety will be assessed throughout the study and serial blood samples and urine samples will be collected for the safety and PK assessment of GMI-1271.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy adult male and/or females, 19 to 60 years of age, inclusive.
2. Medically healthy with no clinically significant screening results (e.g., laboratory profiles, medical histories, vital signs, ECGs, physical examination) as deemed by the PI.
3. Females of childbearing potential must either be sexually inactive (abstinent) for 3 months prior to dosing or be using an acceptable birth control method
4. Females must have a negative pregnancy test at the time of screening and prior to dosing for inclusion in the study.
5. Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.

Exclusion Criteria:

1. Subject is mentally or legally incapacitated or has significant emotional problems at the time of screening visit or expected during the conduct of the study.
2. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI.
3. History of any illness that, in the opinion of the PI, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
4. Hemoglobin level below the lower limit of normal at screening or check-in.
5. Any liver function test (e.g., AST, ALT, bilirubin) 1.5x the upper limit of normal at screening or check-in.
6. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
7. Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.
8. Heart rate is lower than 40 bpm or higher than 99 bpm at screening.
9. QTc interval >430 msec for males or >450 msec for females, or history of prolonged QT syndrome.
10. Estimated creatinine clearance < 90 ml/min at screening or check-in.
11. Blood donation or significant blood loss within 56 days prior to dosing.
12. Plasma donation within 7 days prior to dosing.
13. Participation in another clinical trial within 28 days prior to dosing. The 28-day window will be derived from the date of the last study procedure (such as last blood collection or dosing) in the previous study to Day 1 of Period 1 of the current study.

Note: If an increase (>1.5 x N) in bilirubin is present at screening additional liver function tests may be performed (such as ALT, AST, ALP, albumin, and direct and indirect bilirubin) to determine if the increase of bilirubin is due to Gilbert-Meulengracht syndrome. If consistent with Gilbert's syndrome, the Investigator and Sponsor may decide not to consider this as an exclusion. Any such decision will be documented in the study record.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 2 mg/kg GMI-1271 or matching placebo	Drug: Placebo; Drug: GMI-1271; GMI-1271 is a potent, rationally designed glycomimetic E-selectin antagonist
Experimental: Cohort 2; 5 mg/kg GMI-1271 or matching placebo	Drug: Placebo; Drug: GMI-1271; GMI-1271 is a potent, rationally designed glycomimetic E-selectin antagonist
Experimental: Cohort 3; 10 mg/kg GMI-1271 or matching placebo	Drug: Placebo; Drug: GMI-1271; GMI-1271 is a potent, rationally designed glycomimetic E-selectin antagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment related adverse events	Treatment related adverse events as a measure of safety and tolerability of GMI-1271 (time frame: Day 1-15)	Day 1-15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of peak plasma concentration (Tmax)		Day 1-3
Pharmacodynamics	WBC count, biomarkers to assess pharmacodynamics of single IV dose of GMI-1271 (time frame: Day 1-3)	Day 1-3
Peak plasma concentration (Cmax)		Day 1-3
Area under the plasma concentration vs time curve (AUC)		Day 1-3

Collaborators and Investigators

• Sponsor: GlycoMimetics Incorporated

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: June 17, 2014
• First Submitted That Met QC Criteria: June 19, 2014
• First Posted (Estimate): June 20, 2014

Study Record Updates

• Last Update Posted (Actual): February 27, 2018
• Last Update Submitted That Met QC Criteria: February 23, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: healthy volunteers, GMI-1271
• Other Study ID Numbers: GMI-1271-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No