Clinical trial NCT02567682: Drug Interaction Study of GBT440 With Caffeine, S-warfarin, Omeprazole, and Midazolam in Healthy Subjects
Official title: A Phase 1, Open-Label Study to Evaluate the Effect of Multiple Doses of GBT440 on the Pharmacokinetics of Probe Substrates for CYP1A2, CYP2C9, CYP2C19, and CYP3A4 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sickle Cell Disease
Keywords: anemia, sickle cell
Lead sponsor: Global Blood Therapeutics
Sponsor class: INDUSTRY
First posted: 2015-10-05
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Peak plasma concentration(Cmax) for caffeine, S warfarin, omeprazole, and midazolam in plasma
timeFrame: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
measure: 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
timeFrame: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
measure: Area under the plasma concentration time curve from time 0 extrapolated to infinity (AUCinf) for caffeine, S warfarin, omeprazole, and midazolam
timeFrame: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Secondary outcomes:
measure: The time that Cmax was observed (tmax) for caffeine, S warfarin, omeprazole, and midazolam in plasma
timeFrame: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
measure: Terminal elimination half-life (t½) for caffeine, S warfarin, omeprazole, and midazolam in plasma
timeFrame: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
measure: Cmax for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
timeFrame: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
measure: tmax, for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
timeFrame: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
measure: AUCt for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
timeFrame: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
measure: AUCinf for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
timeFrame: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
measure: t1/2 for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
timeFrame: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
measure: Ratio of metabolite to parent Cmax corrected for molecular weight (Cmax M/P) for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
timeFrame: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
measure: Ratio of metabolite to parent AUCt corrected for molecular weight (AUCt M/P)for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
timeFrame: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
measure: Ratio of metabolite to parent AUCinf corrected for molecular weight (AUCinf M/P) for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
timeFrame: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
measure: Cmax for GBT440 in whole blood and plasma
timeFrame: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
measure: tmax for GBT440 in whole blood and plasma
timeFrame: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
measure: AUC from time 0 to 24 hours (AUC0-24) (Days 4 and 7) for GBT440 in whole blood and plasma
timeFrame: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
measure: t1/2 (Day7) for GBT440 in whole blood and plasma
timeFrame: 0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Other outcomes:
measure: Treatment-emergent adverse events (TEAEs) and serious adverse events
timeFrame: Baseline to Period 2 Day 25
measure: Change in clinical laboratory tests
timeFrame: Baseline to Period 2 Day 25
measure: Change in physical examination findings
timeFrame: Baseline to Period 2 Day 25
measure: Change in vital signs
timeFrame: Baseline to Period 2 Day 25
measure: Change in pulse oximetry findings
timeFrame: Baseline to Period 2 Day 25
measure: Change in electrocardiograms (ECGs)
timeFrame: Baseline to Period 2 Day 25
Locations:
city: San Antonio
country: United States
facility: ICON Early Phase Services, LLC Clinical Research Unit
state: Texas
Study officials:
affiliation: Global Blood Therapeutics
name: Carla Washington, PhD
role: STUDY_DIRECTOR
References: