Single-Dose PK Study of GBT440 in Subjects With Renal 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, moderate, or severe renal impairment disease and healthy subjects with normal renal function.

Detailed Description
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Up to 40 adult 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 Non-Randomized, Open-Label, Parallel Group, Single-Dose Study to Compare the Pharmacokinetics of GBT440 in Subjects With Renal Impaired Function to Healthy Subjects

Conditions
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Renal 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 80 years old Willing and able to give written informed consent Subjects with renal impairment: Severe renal impairment (eGFR < 30 mL/min/1.73m2, not on dialysis) Moderate renal impairment (30 mL/min/1.73m2 = or < eGFR < 60 mL/min/1.73m2) Mild renal impairment (60 mL/min/1.73m2 = or < eGFR < 90 mL/min/1.73m2) Healthy subjects: Match in age, gender and body mass index with renal 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 Subjects with renal impairment: - History of clinically significant hepatic disease e.g. hepatitis, cirrhosis and or liver enzymes (ALT, AST, GGT and total bilirubin) > 5 times the upper limit of normal within the past year

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Severe Renal Impairment<br>eGFR < 30 mL/min/1.73m2, not on dialysis | Drug: GBT440<br>* Oral<br>|
| Experimental: GBT440 Dose 1: Moderate Renal Impairment<br>30 mL/min/1.73m2 = or < eGFR < 60 mL/min/1.73m2 | Drug: GBT440<br>* Oral<br>|
| Experimental: GBT440 Dose 1: Mild Renal Impairment<br>60 mL/min/1.73m2 = or < eGFR < 90 mL/min/1.73m2 | Drug: GBT440<br>* Oral<br>|
| Experimental: GBT440 Dose 1: Normal Renal function<br>eGFR > or = 90 mL/min/1.73m2 | Drug: GBT440<br>* Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of GBT440 in subjects with severe, moderate, or mild renal impairment versus subjects with normal renal function | Maximum observed plasma concentration | 28 days max | 
| Tmax of GBT440 in subjects with severe, moderate, or mild renal impairment versus subjects with normal renal function |  | 28 days max | 
| AUC of GBT440 in subjects with severe, moderate, or mild renal impairment versus subjects with normal renal function |  | 28 days max | 
| T1/2 of GBT440 in subjects with severe, moderate, or mild renal impairment versus subjects with normal renal function |  | 28 days max | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with treatment-related Adverse events |  | 28 days max |