Healthy Subjects, Sickle Cell Disease
Conditions
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).
Interventions
DRUGGBT440
GBT440 will be administered as oral capsules
DRUGPlacebo
Matching placebo will be administered as oral capsules
Sponsors
Global Blood Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| Percentage of hemoglobin occupied or modified by GBT440 | 30 days |
| Blood and plasma time to maximum concentration (Tmax) of GBT440 | 30 - 118 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 maximum concentration (Cmax) of GBT440 | 30 - 118 days |
Other
| Measure | Time frame |
|---|---|
| Exercise capacity as measured by 6-minute walk test | 30 - 90 days |
| Percentage of sickled cells under ex vivo conditions | 30 - 90 days |
| Effect of GBT440 on hemolysis as measured by LDH, direct bilirubin, hemoglobin, and reticulocyte count | 30 - 118 days |
| Change from baseline in pain as measured by visual analog scale | 30 days |
| Change from baseline in fatigue as measured by questionnaire | 30 - 118 days |
Countries
United Kingdom
Outcome results
None listed