Study to Evaluate Effects of Investigational Drug on Oxygenation in Healthy Volunteers Under Hypoxic Conditions

Study Overview
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Brief Summary
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To evaluate the effect of GBT440 on oxygen saturation at rest and exercise, under hypoxic conditions, at Day 15 compared to Baseline.

Detailed Description
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This study in healthy subjects will evaluate GBT440 and its effects on cardio-pulmonary function under both normoxic and hypoxic conditions.

Official Title
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An Open Label Study of GBT440 to Evaluate the Effect on Oxygenation in Healthy Subjects at Rest and Maximal Exercise Under Hypoxic Conditions

Conditions
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Cardio-pulmonary Function

Intervention / Treatment
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* Drug: GBT440


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Males or females aged 18 - 50 years inclusive Able and willing to provide signed informed consent to participate in this study VO2 max ≥ 40 mL/kg/min for males, and ≥ 35 mL/kg/min for females Weight ≥ 40 kg Male or female of child bearing potential willing and able to use highly effective methods of contraception during the study to 30 days after the last dose of study drug. EXCLUSION CRITERIA Subjects whose exercise regimen at Screening is, in the Investigator's opinion, expected to change significantly during the study Family or personal history of congenital long QT syndrome Participated in another clinical trial of an investigational drug (or medical device) within 30 days or 5-half-lives, whichever is longer, prior to Screening, or is currently participating in another trial of an investigational drug (or medical device) Clinically significant medical disease that is likely, in the Investigator's opinion, to significantly impact the study's efficacy and safety assessments (e.g., history significant cardio-pulmonary disease or arrhythmias) within 6 months of Screening. AST, ALT or total bilirubin >2 × ULN Serum creatinine >1.5 mg/dL Clinical evidence of active infection, within 21 days of Screening, which may include but is not limited to bronchitis, pneumonia, urinary tract infection, or cellulitis. Female who is breast-feeding or pregnant Current smoker or history of smoking within 3 months from Screening Any condition possibly affecting drug absorption, including but not limited to previous surgery on the stomach or small intestine Known hypersensitivity to any component of the study drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GBT440 Dose 1<br>Dose 1 | Drug: GBT440<br>* Capsules which contain GBT440 drug substance in Swedish Orange<br>* Other names: 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde;|
| Experimental: GBT440 Dose 2<br>Dose 2 | Drug: GBT440<br>* Capsules which contain GBT440 drug substance in Swedish Orange<br>* Other names: 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in oxygen saturation (%) at rest and exercise, under hypoxic conditions |  | Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal oxygen uptake VO2 max (mL/kg/min) under normoxic and hypoxic conditions |  | Day 15 | 
| Cardiac output (L/min) under normoxic and hypoxic conditions |  | Day 15 | 
| Oxy-hemoglobin dissociation curve p50, under hypoxic conditions |  | Day 15 | 
| Perceived dyspnea score (1-10), under normoxic and hypoxic conditions |  | Day 15 | 
| Frequency and severity of treatment-emergent adverse events (TEAEs) as assessed by (NCI CTCAE Version 4.03) |  | Day 15 |