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

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

Official Title
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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

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: GBT440


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multiple-center, nonrandomized, open-label, parallel group study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GBT440 Dose 1:Mild hepatic impairment<br>Child Pugh A | Drug: GBT440<br>* Oral<br>|
| Experimental: GBT440 Dose 1:Moderate hep. impairment<br>Child Pugh B | Drug: GBT440<br>* Oral<br>|
| Experimental: GBT440 Dose 1:Severe hepatic impairment<br>Child Pugh C | Drug: GBT440<br>* Oral<br>|
| Experimental: GBT440 Dose 1:Normal hepatic function<br>Healthy subjects | Drug: GBT440<br>* Oral<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |