A Study of the Safety, Blood Levels and Biological Effects of GBT440 in Healthy Subjects and Subjects With Sickle Cell Disease

Phase 1

Completed

• Conditions: Healthy Subjects; Sickle Cell Disease
• Interventions: Drug: GBT440; Drug: Placebo

• Registration Number: NCT02285088
• Lead Sponsor: Global Blood Therapeutics

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-11-04
• Study First Submitted QC: 2014-11-04
• Study First Posted: 2014-11-06
• Study Start: 2014-12
• Primary Completion: 2017-03
• Study Completion: 2017-05
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-13
• Last Update Posted: 2018-02-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 133

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GBT440	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)
Placebo	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)

Primary Outcome Measures

Name	Time	Method
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	30 - 118 days

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Guy's Hospital; 🇬🇧 London, United Kingdom