Back to resultsA Study of the Safety, Blood Levels and Biological Effects of GBT440 in Healthy Subjects and Subjects With Sickle Cell Disease
Primary Purpose
Healthy Subjects, Sickle Cell Disease
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
GBT440
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Healthy Subjects
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
Sites / Locations
- Guy's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
GBT440
Placebo
Arm Description
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)
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)
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Blood and plasma area under the concentration time curve (AUC) of GBT440
Blood and plasma maximum concentration (Cmax) of GBT440
Blood and plasma time to maximum concentration (Tmax) of GBT440
Percentage of hemoglobin occupied or modified by GBT440
Change from baseline in heart rate and pulse oximetry following exercise testing in healthy volunteers
Full Information
NCT ID
NCT02285088
First Posted
November 4, 2014
Last Updated
February 13, 2018
Sponsor
Global Blood Therapeutics
1. Study Identification
Unique Protocol Identification Number
NCT02285088
Brief Title
A Study of the Safety, Blood Levels and Biological Effects of GBT440 in Healthy Subjects and Subjects With Sickle Cell Disease
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2018
Overall Recruitment Status
Completed
Study Start Date
December 2014 (Actual)
Primary Completion Date
March 2017 (Actual)
Study Completion Date
May 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Global Blood Therapeutics
4. Oversight
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy Subjects, Sickle Cell Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
133 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GBT440
Arm Type
Experimental
Arm Description
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)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
GBT440
Intervention Description
GBT440 will be administered as oral capsules
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo will be administered as oral capsules
Primary Outcome Measure Information:
Title
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 Outcome Measure Information:
Title
Blood and plasma area under the concentration time curve (AUC) of GBT440
Time Frame
30 - 118 days
Title
Blood and plasma maximum concentration (Cmax) of GBT440
Time Frame
30 - 118 days
Title
Blood and plasma time to maximum concentration (Tmax) of GBT440
Time Frame
30 - 118 days
Title
Percentage of hemoglobin occupied or modified by GBT440
Time Frame
30 days
Title
Change from baseline in heart rate and pulse oximetry following exercise testing in healthy volunteers
Time Frame
30 days
Other Pre-specified Outcome Measures:
Title
Percentage of sickled cells under ex vivo conditions
Time Frame
30 - 90 days
Title
Effect of GBT440 on hemolysis as measured by LDH, direct bilirubin, hemoglobin, and reticulocyte count
Time Frame
30 - 118 days
Title
Change from baseline in pain as measured by visual analog scale
Time Frame
30 days
Title
Change from baseline in fatigue as measured by questionnaire
Time Frame
30 - 118 days
Title
Exercise capacity as measured by 6-minute walk test
Time Frame
30 - 90 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Josh Lehrer-Graiwer, MD
Organizational Affiliation
Global Blood Therapeutics
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Timothy Mant, FRCP FFPM
Organizational Affiliation
Guy's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Guy's Hospital
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
30655275
Citation
Howard J, Hemmaway CJ, Telfer P, Layton DM, Porter J, Awogbade M, Mant T, Gretler DD, Dufu K, Hutchaleelaha A, Patel M, Siu V, Dixon S, Landsman N, Tonda M, Lehrer-Graiwer J. A phase 1/2 ascending dose study and open-label extension study of voxelotor in patients with sickle cell disease. Blood. 2019 Apr 25;133(17):1865-1875. doi: 10.1182/blood-2018-08-868893. Epub 2019 Jan 17.
Results Reference
derived
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A Study of the Safety, Blood Levels and Biological Effects of GBT440 in Healthy Subjects and Subjects With Sickle Cell Disease
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