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

Sickle Cell Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02567682
• Other study ID #: GBT440-003
• Status: Completed
• Phase: Phase 1
• First received: September 23, 2015
• Last updated: April 10, 2017
• Start date: September 2015
• Est. completion date: May 2016

Study information

• Verified date: April 2017
• Source: Global Blood Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• GBT440
GBT440 capsules followed by Caffeine, S-warfarin+vitamin K, Omeprazole, and Midazolam

Locations

Country	Name	City	State
United States	ICON Early Phase Services, LLC Clinical Research Unit	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Global Blood Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Treatment-emergent adverse events (TEAEs) and serious adverse events		Baseline to Period 2 Day 25
Other	Change in clinical laboratory tests		Baseline to Period 2 Day 25
Other	Change in physical examination findings		Baseline to Period 2 Day 25
Other	Change in vital signs		Baseline to Period 2 Day 25
Other	Change in pulse oximetry findings		Baseline to Period 2 Day 25
Other	Change in electrocardiograms (ECGs)		Baseline to Period 2 Day 25
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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