Sickle Cell Disease
Conditions
Brief summary
The purpose of this study is to evaluate the relative bioavailability of a single 300 mg dose of GBT440 administered as a high strength (1 × 300 mg) capsule versus a low strength (3 × 100 mg) capsule formulation in healthy fasted subjects.
Interventions
DRUGGBT440
Test: GBT440 300 mg capsule (high-strength) Reference: GBT440 100 mg capsule (low-strength)
Sponsors
Global Blood Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject is a female of non-childbearing potential or male, who is healthy, nonsmoking, and 18 to 60 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 |
|---|---|
| Pharmacokinetics (PK): Maximum observed concentration (Cmax) of GBT440 in whole blood | predose, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose, and Day 12, Day 20, and Day 28 for each period |
| Pharmacokinetics (PK): AUC from time 0 extrapolated to infinity (AUCinf) of GBT440 in whole blood | predose, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose, and Day 12, Day 20, and Day 28 for each period |
| Pharmacokinetics (PK): Area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) of GBT440 in whole blood | predose, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose, and Day 12, Day 20, and Day 28 for each period |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK): Terminal elimination half-life (t½) of GBT440 in whole blood | predose, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose, and Day 12, Day 20, and Day 28 for each period |
| Pharmacokinetics (PK): The time that Cmax was observed (tmax) of GBT440 in whole blood | predose, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose, and Day 12, Day 20, and Day 28 for each period |
| Pharmacokinetics (PK): Apparent oral clearance (CL/F) of GBT440 in whole blood | predose, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose, and Day 12, Day 20, and Day 28 for each period |
| Pharmacokinetics (PK): Apparent volume of distribution during the terminal phase (Vz/F) of GBT440 in whole blood | predose, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose, and Day 12, Day 20, and Day 28 for each period |
Other
| Measure | Time frame |
|---|---|
| Changes in physical examination findings | Baseline to Period 2 Day 28 |
| Changes in clinical laboratory results | Baseline to Period 2 Day 28 |
| Changes in electrocardiograms (ECGs) | Baseline to Period 2 Day 28 |
| Changes in vital signs | Baseline to Period 2 Day 28 |
| Treatment-emergent adverse events (TEAEs) and serious adverse events | Baseline to Period 2 Day 28 |
Countries
United States
Outcome results
None listed