Drug Interaction Study of GBT440 With Caffeine, S-warfarin, Omeprazole, and Midazolam in Healthy Subjects

Phase 1

Completed

• Conditions: Sickle Cell Disease
• Interventions: Drug: GBT440

• Registration Number: NCT02567682
• Lead Sponsor: Global Blood Therapeutics

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-09
• Study First Submitted: 2015-09-23
• Study First Submitted QC: 2015-10-01
• Study First Posted: 2015-10-05
• Primary Completion: 2016-05
• Study Completion: 2016-05
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-10
• Last Update Posted: 2017-04-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fixed sequence, 2-periods	GBT440	An open-label, fixed sequence, 2-period drug interaction study Period 1 Treatment A: Single dose of drug cocktail on Day 1 Period 2 Treatment B: GBT440 on Days 1 through 3 and Treatment C: Single dose of drug cocktail on Day 4 and GBT440 on Days 4 through 7

Primary Outcome Measures

Name	Time	Method
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 (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
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

Secondary Outcome Measures

Name	Time	Method
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
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
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
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
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
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
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
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
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
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
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
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
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

Trial Locations

Locations (1)

ICON Early Phase Services, LLC Clinical Research Unit; 🇺🇸 San Antonio, Texas, United States