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

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

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

Study Overview

• Status: Terminated
• Conditions: Cardio-pulmonary Function
• Intervention / Treatment: Drug: GBT440

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA

1. Males or females aged 18 - 50 years inclusive
2. Able and willing to provide signed informed consent to participate in this study
3. VO2 max ≥ 40 mL/kg/min for males, and ≥ 35 mL/kg/min for females
4. Weight ≥ 40 kg
5. 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

1. Subjects whose exercise regimen at Screening is, in the Investigator's opinion, expected to change significantly during the study
2. Family or personal history of congenital long QT syndrome
3. 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)
4. 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.
5. AST, ALT or total bilirubin >2 × ULN
6. Serum creatinine >1.5 mg/dL
7. 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.
8. Female who is breast-feeding or pregnant
9. Current smoker or history of smoking within 3 months from Screening
10. Any condition possibly affecting drug absorption, including but not limited to previous surgery on the stomach or small intestine
11. Known hypersensitivity to any component of the study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Global Blood Therapeutics
• Collaborators: Mayo Clinic
• Investigators: Study Director: Ganesh Balaratnam, MBChB, BAO, Global Blood Therapeutics

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): February 21, 2018

Study Registration Dates

• First Submitted: January 18, 2017
• First Submitted That Met QC Criteria: February 9, 2017
• First Posted (Actual): February 14, 2017

Study Record Updates

• Last Update Posted (Actual): October 4, 2019
• Last Update Submitted That Met QC Criteria: October 2, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Hypoxia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Pyrazole
• Other Study ID Numbers: GBT440-0111

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO