A Single-Dose Relative Bioavailability Study Of GBT440 300 mg Capsules in Healthy Subjects

A Phase 1, Single-Dose, Open-Label, Randomized, Two-Period Crossover Study to Evaluate the Relative Bioavailability of GBT440 300 mg Administered as Capsule Formulations in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: GBT440

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78209
      • ICON Early Phase Services, LLC Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Sequence 1; Treatment A with one 300 mg capsule (high-strength) of GBT440 administered in a fasted state (test) in dosing Period 1 followed by Treatment B with 300 mg (3 × 100 mg) capsules (low-strength) of GBT440 administered in a fasted state (reference) in dosing Period 2.	Drug: GBT440; Test: GBT440 300 mg capsule (high-strength) Reference: GBT440 100 mg capsule (low-strength)
Experimental: Treatment Sequence 2; Treatment B with 300 mg (3 × 100 mg) capsules (low-strength) of GBT440 administered in a fasted state (reference) in dosing Period 1 followed by Treatment A with one 300 mg capsule (high-strength) of GBT440 administered in a fasted state (test) in dosing Period 2.	Drug: GBT440; Test: GBT440 300 mg capsule (high-strength) Reference: GBT440 100 mg capsule (low-strength)

What is the study measuring?

Primary Outcome Measures

Outcome 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): 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
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

Secondary Outcome Measures

Outcome Measure	Time Frame
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): 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): 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 Outcome Measures

Outcome Measure	Time Frame
Treatment-emergent adverse events (TEAEs) and serious adverse events	Baseline to Period 2 Day 28
Changes in clinical laboratory results	Baseline to Period 2 Day 28
Changes in physical examination findings	Baseline to Period 2 Day 28
Changes in vital signs	Baseline to Period 2 Day 28
Changes in electrocardiograms (ECGs)	Baseline to Period 2 Day 28

Collaborators and Investigators

• Sponsor: Global Blood Therapeutics
• Investigators: Study Director: Carla Washington, PhD, Global Blood Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: September 30, 2015
• First Submitted That Met QC Criteria: October 1, 2015
• First Posted (Estimate): October 5, 2015

Study Record Updates

• Last Update Posted (Actual): April 12, 2017
• Last Update Submitted That Met QC Criteria: April 10, 2017
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: GBT440-004