Study to Evaluate the Safety and Tolerability of GBT440 Administered to Subjects With IPF

Study Overview
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Brief Summary
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This study is a randomized, double-blind, placebo-controlled trial in which eligible IPF subjects will be randomized to receive GBT440 or Placebo orally daily.

Official Title
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A Phase II Randomized, Placebo-Controlled Study of GBT440 to Evaluate the Safety, Tolerability, Pharmacokinetics and Effect on Hypoxemia in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

Conditions
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Idiopathic Pulmonary Fibrosis, Hypoxemia

Intervention / Treatment
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* Drug: GBT440
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of IPF. Oxygen desaturation with exercise. Completion of the baseline 6MWT Weight ≥ 50 kg Male or female of child bearing potential willing and able to use highly effective methods of contraception from study start to 3 months after the last dose of study drug. Exclusion Criteria: FEV1/FVC < 70%. Subjects on supplemental oxygen therapy at rest. History of other interstitial lung diseases. Significant polycythemia. Female who is breast-feeding or pregnant. Known current malignancy or history of malignancy within the last 2 years prior to screening. Use of cytotoxic and/or immunosuppressant medications within 30 days screening. Hospitalization due to an exacerbation of IPF within 30 days of screening Subject plans to begin or has commenced pulmonary rehabilitation within 30 days of screening Corticosteroids (> 10 mg per day of prednisone or an equivalent) within 30 days of screening. Current smoker or history of smoking within 3 months of screening. Currently or, in the opinion of the investigator, soon to be listed for lung transplant. History of unstable or deteriorating cardiac or pulmonary disease (other than IPF) within 6 months of screening. Any condition possibly affecting drug absorption. 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). Subject who, for any reason, is deemed by the investigator to be inappropriate for this study.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GBT440 600 mg Dose<br>Parts A and B | Drug: GBT440<br>* Capsules which contain GBT440 drug substance in Swedish orange<br>|
| Experimental: GBT440 900 mg Dose<br>Part A | Drug: GBT440<br>* Capsules which contain GBT440 drug substance in Swedish orange<br>|
| Experimental: GBT440 1500 mg Dose<br>Part B | Drug: GBT440<br>* Capsules which contain GBT440 drug substance in Swedish orange<br>|
| Placebo Comparator: Placebo<br>Parts A and B | Drug: Placebo<br>* Placebo capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03 |  | Days 1 to 58 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Profile of GBT440 Including Maximum Concentration |  | Days 1 and 28: pre-dose, and 2 hours post dose (+/- 15 minutes); Day 2: 24 hours (+/- 2 hours) after the Day 1 dose and prior to receiving the Day 2 dose; Days 8 & 15: pre-dose only | 
| Pharmacokinetic Profile of GBT440 Including Minimum Concentration |  | Days 1 and 28: pre-dose, and 2 hours post dose (+/- 15 minutes); Day 2: 24 hours (+/- 2 hours) after the Day 1 dose and prior to receiving the Day 2 dose; Days 8 & 15: pre-dose only | 
| Pharmacokinetic Profile of GBT440 Including Apparent Terminal Half Life |  | Days 1 and 28: pre-dose, and 2 hours post dose (+/- 15 minutes); Day 2: 24 hours (+/- 2 hours) after the Day 1 dose and prior to receiving the Day 2 dose; Days 8 & 15: pre-dose only | 
| Evaluate the Effect of GBT440 on Oxygen Saturation Using Pulse Oximetry at Rest | Data reported is change from baseline in Oxygen Saturation at rest | Baseline to Day 28 | 
| Evaluate the Effect of GBT440 on Oxygen Saturation Using Pulse Oximetry After Exercise | Change from Baseline to Day 28 after 6MWT | Baseline to Day 28 |