Single-Dose PK and Safety Study of GBT440 in Subjects With Hepatic Impairment

Phase 1

Completed

• Conditions: Hepatic Impairment
• Interventions: Drug: GBT440

• Registration Number: NCT03114540
• Lead Sponsor: Pfizer

Brief Summary

A Phase 1, multiple center, nonrandomized, open-label, parallel group study of a single oral dose of GBT440 administered in subjects with mild (Child-Pugh A), moderate (Child-Pugh B), or severe (Child-Pugh C) hepatic impairment disease and healthy subjects with normal hepatic function.

Detailed Description

Approximately 24 to 28 subjects will be enrolled. Safety and PK assessments will be performed at selected time points throughout the study.

Study Timeline

• Study Start: 2017-03-17
• Study First Submitted: 2017-03-28
• Study First Submitted QC: 2017-04-10
• Study First Posted: 2017-04-14
• Primary Completion: 2018-02-28
• Study Completion: 2018-03-22
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-14
• Last Update Posted: 2023-07-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

All subjects:

• Males or females, 18 to 75 years old
• Willing and able to give written informed consent

Patients with hepatic impairment:

• Mild hepatic impairment (Child-Pugh A [5-6 points])
• Moderate hepatic impairment (Child-Pugh B [7-9 points])
• Severe hepatic impairment (Child-Pugh C [10-15 points])

Healthy subjects:

• Match in age, gender and body mass index with hepatic impaired subjects
• Healthy and without clinically significant abnormalities in vital signs, ECGs, physical exam, clinical laboratory evaluations, medical and surgical history

Exclusion Criteria

All subjects:

• Participation in another clinical trial of an investigational drug (or medical device) within 30 days of the last dose of investigational drug or 5 half-lives whichever is longer, prior to screening, or is currently participating in another trial of an investigational drug (or medical device)
• Any signs or symptoms of acute illness at screening or Day -1
• History or presence of clinically significant allergic, hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurological disease

Patients with hepatic impairment:

• History of liver transplantation, hepatic mass suggestive of hepatocellular carcinoma or acute liver disease
• Screening serum ALT or AST >5 times the upper limit of normal

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GBT440 Dose 1:Moderate hep. impairment	GBT440	Child Pugh B
GBT440 Dose 1:Mild hepatic impairment	GBT440	Child Pugh A
GBT440 Dose 1:Severe hepatic impairment	GBT440	Child Pugh C
GBT440 Dose 1:Normal hepatic function	GBT440	Healthy subjects

Primary Outcome Measures

Name	Time	Method
To assess the Tmax of GBT440 in patients with mild, moderate, or severe hepatic impairment	28 days max	Time at which maximum concentration was observed
To assess the Cmax of GBT440 in patients with mild, moderate, or severe hepatic impairment	28 days max	Maximum observed plasma concentration
To assess the T1/2 of GBT440 in patients with mild, moderate, or severe hepatic impairment	28 days max	Terminal elimination half-life
To assess the AUC of GBT440 in patients with mild, moderate, or severe hepatic impairment	28 days max	Area under the concentration-time curve

Secondary Outcome Measures

Name	Time	Method
Physical examination findings	28 days max
Clinical laboratory tests	28 days max
Adverse events	28 days max
Vital signs	28 days max
Electrocardiograms	28 days max

Trial Locations

Locations (2)

OCRC; 🇺🇸 Orlando, Florida, United States

University of Miami; 🇺🇸 Miami, Florida, United States