Hepatic Impairment
Conditions
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.
Interventions
DRUGGBT440
Oral
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Multiple-center, nonrandomized, open-label, parallel group study
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| Physical examination findings | 28 days max |
| Electrocardiograms | 28 days max |
| Adverse events | 28 days max |
| Clinical laboratory tests | 28 days max |
| Vital signs | 28 days max |
Countries
United States
Outcome results
None listed