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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: GBT440


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Sequence 1<br>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<br>* Test: GBT440 300 mg capsule (high-strength) Reference: GBT440 100 mg capsule (low-strength)<br>|
| Experimental: Treatment Sequence 2<br>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<br>* Test: GBT440 300 mg capsule (high-strength) Reference: GBT440 100 mg capsule (low-strength)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |