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

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the effect of hepatic impairment on rivipansel PK and safety.

Official Title
-----------------
A Phase 1, Non-randomized, Open-label, Parallel-group Single-dose Study To Evaluate The Pharmacokinetics, Safety, And Tolerability Of Intravenous Rivipansel (Pf-06460031) In Subjects With Moderate Hepatic Impairment And In Healthy Subjects With Normal Hepatic Function

Conditions
-----------------
Moderate Hepatic Impairment, Normal Hepatic Function

Intervention / Treatment
-----------------
* Drug: Rivipansel


Participation Criteria
=================
Eligibility Criteria
-----------------
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

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Moderate Hepatic Impairment<br>A single dose of IV Rivipansel over 20 minutes | Drug: Rivipansel<br>* A single dose of IV Rivipansel over 20 minutes<br>* Other names: GMI-1070;|
| Experimental: Normal Hepatic Function<br>A single dose of IV Rivipansel over 20 minutes | Drug: Rivipansel<br>* A single dose of IV Rivipansel over 20 minutes<br>* Other names: GMI-1070;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | Day 5 | 
| 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. | 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. | Day 5 | 
| Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Rivipansel | AUCinf was calculated as AUClast + (Clast*/kel), where Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log linear regression analysis, kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. | Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1 | 
| Total Clearance From Plasma (CL) of Rivipansel | CL of rivipansel was calculated as dose/AUCinf, where AUCinf referred to the area under the plasma concentration-time profile from time 0 extrapolated to the infinite time. | Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 |  | 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. | 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. | Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatic Impairment, Rivipansel