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

NCT02871570 | Completed Phase 1 Results

• 1 other identifier: B5201006
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Moderate Hepatic Impairment; Normal Hepatic Function

Keywords

Hepatic Impairment; Rivipansel

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (4)

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

  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

  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

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

Other Outcomes (1)

• Time for Maximum Observed Concentration (Tmax) of Rivipansel

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

Study Arms (2)

Moderate Hepatic Impairment

EXPERIMENTAL

A single dose of IV Rivipansel over 20 minutes

Drug: Rivipansel

Normal Hepatic Function

EXPERIMENTAL

A single dose of IV Rivipansel over 20 minutes

Drug: Rivipansel

Interventions

Rivipansel DRUG

A single dose of IV Rivipansel over 20 minutes

Also known as: GMI-1070

Moderate Hepatic Impairment; Normal Hepatic Function

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlycoMimetics Incorporated: lead

Study Sites (1)

Orlando Clincial Research Center

Orlando, Florida, 32809, United States

Location

Related Publications (1)

• Tammara BK, Ryan K, Plotka A, Shafer FE, Wei H, Readett D, Fang A, Korth-Bradley JM. Effect of Renal or Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Intravenous Rivipansel. Clin Pharmacol Drug Dev. 2020 Nov;9(8):918-928. doi: 10.1002/cpdd.842. Epub 2020 Jun 24.

  PMID: 32579796 DERIVED

MeSH Terms

Interventions

rivipansel

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2016
• First Posted: August 18, 2016
• Study Start: September 1, 2016
• Primary Completion: February 1, 2017
• Study Completion: March 1, 2017
• Last Updated: July 9, 2020
• Results First Posted: November 28, 2018

Record last verified: 2020-06

Locations

US (1)