A Study to Evaluate the Effect of IV Doses of Rivipansel in Subjects With Moderate Hepatic Impairment and in Healthy Subjects With Normal Hepatic Function

Phase 1CompletedNCT02871570

GlycoMimetics Incorporated16 enrolled

Overview

The purpose of this study is to determine the effect of hepatic impairment on rivipansel PK and safety.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Moderate Hepatic Impairment Normal Hepatic Function

Interventions

RivipanselDRUG

A single dose of IV Rivipansel over 20 minutes

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Female subjects of non-childbearing potential or male subjects * Body Mass Index (BMI) of 17.5 to 40.0 kg/m2 * Normal Hepatic function for the healthy subjects * Stable Hepatic Impairment for the subjects with moderate hepatic impairment Exclusion Criteria: * Treatment with an investigational drug within 30 days of the dose of study medication * Pregnant females, breastfeeding female subjects and male subjects with partners currently pregnant * Use of herbal supplements in the 28 days prior to the dose of study medication * Blood donation (excluding plasma donation) of approximately 1 pint or more within 56 days prior to study medication * A positive urine drug screen for illicit drugs

Locations (1)

Orlando Clincial Research Center

Orlando, Florida, United States

Outcomes

Primary Outcomes

Number of Participants With Post-baseline Clinically Significant Findings in Physical Examinations

A full physical examination was performed for each participant, and it included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes and gastrointestinal, musculoskeletal, and neurological systems. Clinical significance of laboratory findings was determined by the investigator.

Time frame: Day 5

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of its causal relationship with study treatment. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; was life-threatening (immediate risk of death); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events between administration of study medication and up to follow-up visit (28-31 days after administration) that were absent before treatment or that worsened after treatment. AEs included both serious and non-serious AEs.

Time frame: Day 1 to follow-up visit (28-31 days after administration of study medication on Day 1)

Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria

Maximum absolute values and increases from baseline were summarized for PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization), QRS duration (time from Q wave to the end of S wave, corresponding to ventricle depolarization), and QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with ECG findings meeting the following criteria is presented: (1) PR interval \>=300 msec; (2) QRS duration \>=200 msec; (3) QTcF interval: 450 to \<480 msec; (4) QTcF interval: 480 to \<500 msec; (5) QTcF interval \>=500 msec; (6) PR interval percent increase from baseline \>=25/50 percent; (7) QRS duration percent increase from baseline \>=50 percent; (8) QTcF interval increase from baseline: 30 to \<60 msec; (9) QTcF interval increase from baseline \>=60 msec.

Data from ClinicalTrials.gov

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Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria

Absolute values and changes from baseline (increase and decrease) were summarized for supine diastolic blood pressure (DBP), supine systolic blood pressure (SBP), and supine pulse rate. Number of participants with vital signs findings meeting the following criteria is presented: (1) supine DBP \<50 millimeters of mercury (mm Hg); (2) supine DBP \>90 mm Hg; (3) supine SBP \<90 mm Hg; (4) supine SBP \>140 mm Hg (for normal hepatic function group); (5) supine SBP \>160 mm Hg (for moderate hepatic impairment group); (6) supine pulse rate \< 40 beats per minute (bpm); (7) supine pulse rate \>120 bpm; (8) supine DBP increase from baseline \>=20 mm Hg; (9) supine SBP increase from baseline \>=30 mmHg; (10) supine DBP decrease from baseline \>=20 mm Hg; (11) supine SBP decrease from baseline \>=30 mm Hg.

Time frame: Day 1 to Day 5

Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)

Laboratory tests included: hematology (hemoglobin, hematocrit, red and white blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, prothrombin time/international normalized ratio), chemistry (blood urea nitrogen/urea and creatinine, fasting glucose, calcium, sodium, potassium, chloride, total carbon dioxide, aspartate and alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein), urinalysis (pH, qualitative glucose, protein, and blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, and microscopy), and other tests (follicle stimulating hormone, urine drug test and serologic tests on human immunodeficiency virus-1 antibody, Hepatitis B surface antigen and hepatitis C antibody). Abnormality was determined by the investigator using widely accepted criteria in clinical practice.

Time frame: Day 5

Secondary Outcomes

Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Rivipansel

Area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (AUClast) of rivipansel was determined using a linear/log trapezoidal method.

Time frame: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1

Maximum Observed Concentration (Cmax) of Rivipansel

Time frame: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1

Terminal Half-Life of Rivipansel

Terminal half-life of rivipansel was calculated as loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.

Time frame: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1

Volume of Distribution at Steady State (Vss) of Rivipansel

Vss of rivipansel was calculated as CL\*MRT, where MRT was the mean residence time and CL was the clearance from plasma.

Time frame: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1