Sickle Cell Disease
Conditions
Keywords
anemia, sickle cell
Brief summary
The purpose of this study to evaluate the effect of concomitant administration of GBT440 on caffeine (a CYP1A2 probe substrate), S warfarin (a CYP2C9 probe substrate), omeprazole (a CYP2C19 probe substrate), and midazolam (a CYP3A4 probe substrate) plasma concentrations.
Interventions
DRUGGBT440
GBT440 capsules followed by Caffeine, S-warfarin+vitamin K, Omeprazole, and Midazolam
Sponsors
Global Blood Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject is a female of non-childbearing potential or male, who is healthy, nonsmoking, and 18 to 55 years old, inclusive, at screening * Male subjects agree to use contraception * Willing and able to give written informed consent
Exclusion criteria
* Evidence or history of clinically significant metabolic, allergic, dermatological, hepatic, renal,hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder * History of hypersensitivity or allergy to drugs, foods, or other substances * History or presence of abnormal electrocardiogram or hypertension * History of alcohol abuse, illicit drug use, significant mental illness, physical dependence to any opioid, or any history of drug abuse or addiction within 1 year of screening * Participated in another clinical trial of an investigational drug within 30 days (or 5 half-lives of the investigational drug, whichever is longer) prior to Screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Peak plasma concentration(Cmax) for caffeine, S warfarin, omeprazole, and midazolam in plasma | 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2 |
| Area under the plasma concentration time curve from time 0 extrapolated to infinity (AUCinf) for caffeine, S warfarin, omeprazole, and midazolam | 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2 |
| Area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for caffeine, S warfarin, omeprazole, and midazolam | 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2 |
Secondary
| Measure | Time frame |
|---|---|
| AUCinf for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma | 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2 |
| Ratio of metabolite to parent AUCt corrected for molecular weight (AUCt M/P)for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma | 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2 |
| Ratio of metabolite to parent AUCinf corrected for molecular weight (AUCinf M/P) for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma | 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2 |
| Cmax for GBT440 in whole blood and plasma | 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2 |
| tmax for GBT440 in whole blood and plasma | 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2 |
| AUC from time 0 to 24 hours (AUC0-24) (Days 4 and 7) for GBT440 in whole blood and plasma | 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2 |
| t1/2 (Day7) for GBT440 in whole blood and plasma | 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2 |
| The time that Cmax was observed (tmax) for caffeine, S warfarin, omeprazole, and midazolam in plasma | 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2 |
| Terminal elimination half-life (t½) for caffeine, S warfarin, omeprazole, and midazolam in plasma | 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2 |
| Cmax for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma | 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2 |
| tmax, for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma | 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2 |
| AUCt for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma | 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2 |
| t1/2 for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma | 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2 |
| Ratio of metabolite to parent Cmax corrected for molecular weight (Cmax M/P) for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma | 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2 |
Other
| Measure | Time frame |
|---|---|
| Change in pulse oximetry findings | Baseline to Period 2 Day 25 |
| Change in electrocardiograms (ECGs) | Baseline to Period 2 Day 25 |
| Change in vital signs | Baseline to Period 2 Day 25 |
| Treatment-emergent adverse events (TEAEs) and serious adverse events | Baseline to Period 2 Day 25 |
| Change in physical examination findings | Baseline to Period 2 Day 25 |
| Change in clinical laboratory tests | Baseline to Period 2 Day 25 |
Countries
United States
Outcome results
None listed