A Phase I Randomised, Placebo-controlled, Double-blind, Single and Multiple Ascending Dose Study of the Tolerability and Pharmacokinetics of GBT440 in Healthy Subjects and Patients With Sickle Cell Disease

Global Blood Therapeutics1 site in 1 country133 target enrollmentDecember 2014

ConditionsHealthy Subjects Sickle Cell Disease

InterventionsGBT440 Placebo

DrugsGBT440 Placebo

Overview

Phase: Phase 1
Intervention: GBT440
Conditions: Healthy Subjects
Sponsor: Global Blood Therapeutics
Enrollment: 133
Locations: 1
Primary Endpoint: Safety, as assessed by frequency and severity of adverse events (AEs), and changes in vital signs, 12-lead electrocardiograms (ECGs), and laboratory assessments as compared to baseline
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic effects of GBT440 compared with placebo in healthy subjects and subjects with sickle cell disease (SCD).

Registry

clinicaltrials.gov

Start Date

December 2014

End Date

May 2017

Last Updated

8 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Global Blood Therapeutics

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Healthy male or female of non-child bearing potential; 18 to 55 years old; are non-smokers and have not used nicotine products within 3 months prior to screening.
•Male or female, 18 to 60 years old, with sickle cell disease (hemoglobin SS, HbS/β0thalassemia, HbS/β+thalassemia, or HbSC) not requiring chronic blood transfusion therapy; without hospitalization in 30 days before screening or receiving blood transfusion within 30 days before screening; subjects are allowed concomitant use of hydroxyurea if the dose has been stable for the 3 months prior to screening.

Exclusion Criteria

•Subjects who have a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders.
•Subjects who consume more than 14 (female subjects) or 21 (male subjects) units of alcohol a week.
•Subjects who have used any investigational product in any clinical trial within 30 days of screening
•Subjects with sickle cell disease who smoke \>10 cigarettes per day; have hemoglobin level \<6 g/dL or \>10.4 g/dL (\> ULN (appropriately corrected for gender) for Cohort 15) at screening; have aspartate aminotransferase (AST) \>4x upper limit of normal or alanine aminotransferase (ALT), or alkaline phosphatase (ALK) \>3x upper limit of normal reference range (ULN) at screening; have moderate or severe renal dysfunction

Arms & Interventions

GBT440

Subjects randomized 6:2 to receive daily oral dosing of GBT440 or placebo for 1 day (single dose) and up to 118 days (multiple dose)

Intervention: GBT440

Placebo

Subjects randomized 6:2 to receive daily oral dosing of GBT440 or placebo for 1 day (single dose) and up to 118 days (multiple dose)

Intervention: Placebo

Outcomes

Primary Outcomes

Safety, as assessed by frequency and severity of adverse events (AEs), and changes in vital signs, 12-lead electrocardiograms (ECGs), and laboratory assessments as compared to baseline

Time Frame: 30 - 118 days

Secondary Outcomes

Blood and plasma maximum concentration (Cmax) of GBT440(30 - 118 days)
Percentage of hemoglobin occupied or modified by GBT440(30 days)
Change from baseline in heart rate and pulse oximetry following exercise testing in healthy volunteers(30 days)
Blood and plasma area under the concentration time curve (AUC) of GBT440(30 - 118 days)
Blood and plasma time to maximum concentration (Tmax) of GBT440(30 - 118 days)