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

Primary Purpose

Sickle Cell Disease

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
GBT440
Sponsored by
Global Blood Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Disease focused on measuring anemia, sickle cell

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • ICON Early Phase Services, LLC Clinical Research Unit

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fixed sequence, 2-periods

Arm Description

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

Outcomes

Primary Outcome Measures

Peak plasma concentration(Cmax) for caffeine, S warfarin, omeprazole, and midazolam in plasma
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
Area under the plasma concentration time curve from time 0 extrapolated to infinity (AUCinf) for caffeine, S warfarin, omeprazole, and midazolam

Secondary Outcome Measures

The time that Cmax was observed (tmax) for caffeine, S warfarin, omeprazole, and midazolam in plasma
Terminal elimination half-life (t½) for caffeine, S warfarin, omeprazole, and midazolam in plasma
Cmax for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
tmax, for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
AUCt for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
AUCinf for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
t1/2 for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
Ratio of metabolite to parent Cmax corrected for molecular weight (Cmax M/P) for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
Ratio of metabolite to parent AUCt corrected for molecular weight (AUCt M/P)for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
Ratio of metabolite to parent AUCinf corrected for molecular weight (AUCinf M/P) for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
Cmax for GBT440 in whole blood and plasma
tmax for GBT440 in whole blood and plasma
AUC from time 0 to 24 hours (AUC0-24) (Days 4 and 7) for GBT440 in whole blood and plasma
t1/2 (Day7) for GBT440 in whole blood and plasma

Full Information

First Posted
September 23, 2015
Last Updated
April 10, 2017
Sponsor
Global Blood Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT02567682
Brief Title
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

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
September 2015 (undefined)
Primary Completion Date
May 2016 (Actual)
Study Completion Date
May 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Global Blood Therapeutics

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
Keywords
anemia, sickle cell

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fixed sequence, 2-periods
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
GBT440
Intervention Description
GBT440 capsules followed by Caffeine, S-warfarin+vitamin K, Omeprazole, and Midazolam
Primary Outcome Measure Information:
Title
Peak plasma concentration(Cmax) for caffeine, S warfarin, omeprazole, and midazolam in plasma
Time Frame
0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Title
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
Time Frame
0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Title
Area under the plasma concentration time curve from time 0 extrapolated to infinity (AUCinf) for caffeine, S warfarin, omeprazole, and midazolam
Time Frame
0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Secondary Outcome Measure Information:
Title
The time that Cmax was observed (tmax) for caffeine, S warfarin, omeprazole, and midazolam in plasma
Time Frame
0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Title
Terminal elimination half-life (t½) for caffeine, S warfarin, omeprazole, and midazolam in plasma
Time Frame
0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Title
Cmax for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
Time Frame
0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Title
tmax, for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
Time Frame
0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Title
AUCt for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
Time Frame
0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Title
AUCinf for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
Time Frame
0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Title
t1/2 for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
Time Frame
0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Title
Ratio of metabolite to parent Cmax corrected for molecular weight (Cmax M/P) for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
Time Frame
0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Title
Ratio of metabolite to parent AUCt corrected for molecular weight (AUCt M/P)for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
Time Frame
0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Title
Ratio of metabolite to parent AUCinf corrected for molecular weight (AUCinf M/P) for metabolites of caffeine, warfarin, omeprazole, and midazolam in plasma
Time Frame
0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Title
Cmax for GBT440 in whole blood and plasma
Time Frame
0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Title
tmax for GBT440 in whole blood and plasma
Time Frame
0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Title
AUC from time 0 to 24 hours (AUC0-24) (Days 4 and 7) for GBT440 in whole blood and plasma
Time Frame
0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Title
t1/2 (Day7) for GBT440 in whole blood and plasma
Time Frame
0 - 168 hours post dose in Period 1 and 0-408 hours post dose in Period 2
Other Pre-specified Outcome Measures:
Title
Treatment-emergent adverse events (TEAEs) and serious adverse events
Time Frame
Baseline to Period 2 Day 25
Title
Change in clinical laboratory tests
Time Frame
Baseline to Period 2 Day 25
Title
Change in physical examination findings
Time Frame
Baseline to Period 2 Day 25
Title
Change in vital signs
Time Frame
Baseline to Period 2 Day 25
Title
Change in pulse oximetry findings
Time Frame
Baseline to Period 2 Day 25
Title
Change in electrocardiograms (ECGs)
Time Frame
Baseline to Period 2 Day 25

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carla Washington, PhD
Organizational Affiliation
Global Blood Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
ICON Early Phase Services, LLC Clinical Research Unit
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78209
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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