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

NCT03114540 — Phase 1, Completed, 29 participants, Pfizer

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A Phase 1, Open-Label Study to Characterize the Pharmacokinetics and Safety of a Single Oral Dose of GBT440 in Subjects With Hepatic Impairment

Registry	NCT03114540
Status	Completed
Phase	Phase 1
Study type	Interventional; non randomized, parallel, masking: none, other
Enrollment	29 (Actual)
Sponsor	Pfizer (Industry)
Conditions	Hepatic Impairment
Interventions	GBT440 (Drug)
Dates	start 2017-03-17, primary completion 2018-02-28, completion 2018-03-22, first posted 2017-04-14, last updated 2023-07-18
Locations	2 sites in United States

-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.

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+Detailed description

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

+Arms and interventions

Arm	Type	Interventions	Description
GBT440 Dose 1:Mild hepatic impairment	Experimental	Drug: GBT440	Child Pugh A
GBT440 Dose 1:Moderate hep. impairment	Experimental	Drug: GBT440	Child Pugh B
GBT440 Dose 1:Severe hepatic impairment	Experimental	Drug: GBT440	Child Pugh C
GBT440 Dose 1:Normal hepatic function	Experimental	Drug: GBT440	Healthy subjects

GBT440 (Drug): Oral

+Outcome measures

Primary outcomes

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 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 AUC of GBT440 in patients with mild, moderate, or severe hepatic impairment [28 days max]: Area under the concentration-time curve
To assess the T1/2 of GBT440 in patients with mild, moderate, or severe hepatic impairment [28 days max]: Terminal elimination half-life

Secondary outcomes

Adverse events [28 days max]
Clinical laboratory tests [28 days max]
Physical examination findings [28 days max]
Vital signs [28 days max]
Electrocardiograms [28 days max]

+Eligibility

Sex: All, ages: 18 Years to 75 Years, accepts healthy volunteers

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

+Locations (2)

Facility	City	Country	Status
University of Miami	Miami, Florida	United States
OCRC	Orlando, Florida	United States

+Investigators

Pfizer CT.gov Call Center, Study director, Pfizer