Single-Dose PK Study of GBT440 in Subjects With Renal Impairment

Phase 1

Completed

• Conditions: Renal Impairment
• Interventions: Drug: GBT440

• Registration Number: NCT03161015
• Lead Sponsor: Global Blood Therapeutics

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, moderate, or severe renal impairment disease and healthy subjects with normal renal function.

Detailed Description

Up to 40 adult subjects will be enrolled. Safety and PK assessments will be performed at selected time points throughout the study.

Study Timeline

• Study Start: 2016-11
• Study First Submitted: 2017-05-08
• Study First Submitted QC: 2017-05-17
• Study First Posted: 2017-05-19
• Primary Completion: 2017-05-25
• Study Completion: 2017-07-06
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-20
• Last Update Posted: 2018-02-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GBT440 Dose 1: Moderate Renal Impairment	GBT440	30 mL/min/1.73m2 = or \< eGFR \< 60 mL/min/1.73m2
GBT440 Dose 1: Mild Renal Impairment	GBT440	60 mL/min/1.73m2 = or \< eGFR \< 90 mL/min/1.73m2
GBT440 Dose 1: Severe Renal Impairment	GBT440	eGFR \< 30 mL/min/1.73m2, not on dialysis
GBT440 Dose 1: Normal Renal function	GBT440	eGFR \> or = 90 mL/min/1.73m2

Primary Outcome Measures

Name	Time	Method
Cmax of GBT440 in subjects with severe, moderate, or mild renal impairment versus subjects with normal renal function	28 days max	Maximum observed plasma concentration
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

Name	Time	Method
Number of subjects with treatment-related Adverse events	28 days max

Trial Locations

Locations (2)

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

OCRC; 🇺🇸 Orlando, Florida, United States