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

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: GBT440

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 Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Orlando, Florida, United States, 32809
      • OCRC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: GBT440 Dose 1: Severe Renal Impairment; eGFR < 30 mL/min/1.73m2, not on dialysis	Drug: GBT440; Oral
EXPERIMENTAL: GBT440 Dose 1: Moderate Renal Impairment; 30 mL/min/1.73m2 = or < eGFR < 60 mL/min/1.73m2	Drug: GBT440; Oral
EXPERIMENTAL: GBT440 Dose 1: Mild Renal Impairment; 60 mL/min/1.73m2 = or < eGFR < 90 mL/min/1.73m2	Drug: GBT440; Oral
EXPERIMENTAL: GBT440 Dose 1: Normal Renal function; eGFR > or = 90 mL/min/1.73m2	Drug: GBT440; Oral

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Global Blood Therapeutics
• Investigators: Study Director: Carla Washington, Global Blood Therapeutics

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2016
• Primary Completion (ACTUAL): May 25, 2017
• Study Completion (ACTUAL): July 6, 2017

Study Registration Dates

• First Submitted: May 8, 2017
• First Submitted That Met QC Criteria: May 17, 2017
• First Posted (ACTUAL): May 19, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 22, 2018
• Last Update Submitted That Met QC Criteria: February 20, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: GBT440-0110

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No