Hypoxemia, Idiopathic Pulmonary Fibrosis
Conditions
Brief summary
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.
Interventions
DRUGGBT440
Capsules which contain GBT440 drug substance in Swedish orange
DRUGPlacebo
Placebo capsules
Sponsors
Global Blood Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03 | Days 1 to 58 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline to Day 28 | Data reported is change from baseline in Oxygen Saturation at rest |
| Evaluate the Effect of GBT440 on Oxygen Saturation Using Pulse Oximetry After Exercise | Baseline to Day 28 | Change from Baseline to Day 28 after 6MWT |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Parts A and B
Placebo: Placebo capsules | 10 |
| GBT440 600 mg Dose Parts A and B Dose 1
GBT440: Capsules which contain GBT440 drug substance in Swedish orange | 9 |
| GBT440 900 mg Dose Part A Dose 2
GBT440: Capsules which contain GBT440 drug substance in Swedish orange | 6 |
| GBT440 1500 mg Dose Part B Dose 2; Overall Dose 3
GBT440: Capsules which contain GBT440 drug substance in Swedish orange | 14 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Other | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 4 | 0 |
Baseline characteristics
| Characteristic | Placebo | GBT440 600 mg Dose | GBT440 900 mg Dose | GBT440 1500 mg Dose | Total |
|---|---|---|---|---|---|
| Age, Continuous | 71.0 years | 72.0 years | 64.5 years | 69.5 years | 71.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 9 Participants | 6 Participants | 14 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 00 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 9 Participants | 6 Participants | 14 Participants | 39 Participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 1 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 9 Participants | 6 Participants | 5 Participants | 11 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 9 | 0 / 6 | 0 / 14 |
| other Total, other adverse events | 8 / 10 | 7 / 9 | 4 / 6 | 11 / 14 |
| serious Total, serious adverse events | 0 / 10 | 2 / 9 | 1 / 6 | 2 / 14 |
Outcome results
Primary
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03
Time frame: Days 1 to 58
Population: Participant had at least one dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03 | 8 Participants |
| GBT440 600 mg Dose | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03 | 7 Participants |
| GBT440 900mg Dose | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03 | 4 Participants |
| GBT440 1500mg Dose | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03 | 11 Participants |
Secondary
Evaluate the Effect of GBT440 on Oxygen Saturation Using Pulse Oximetry After Exercise
Change from Baseline to Day 28 after 6MWT
Time frame: Baseline to Day 28
Population: 6MWT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Evaluate the Effect of GBT440 on Oxygen Saturation Using Pulse Oximetry After Exercise | -1.7 percent oxygen (%) | Standard Error 1.64 |
| GBT440 600 mg Dose | Evaluate the Effect of GBT440 on Oxygen Saturation Using Pulse Oximetry After Exercise | 2.9 percent oxygen (%) | Standard Error 2.11 |
| GBT440 900mg Dose | Evaluate the Effect of GBT440 on Oxygen Saturation Using Pulse Oximetry After Exercise | 3.5 percent oxygen (%) | Standard Error 2.16 |
| GBT440 1500mg Dose | Evaluate the Effect of GBT440 on Oxygen Saturation Using Pulse Oximetry After Exercise | 3.5 percent oxygen (%) | Standard Error 1.56 |
Secondary
Evaluate the Effect of GBT440 on Oxygen Saturation Using Pulse Oximetry at Rest
Data reported is change from baseline in Oxygen Saturation at rest
Time frame: Baseline to Day 28
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Evaluate the Effect of GBT440 on Oxygen Saturation Using Pulse Oximetry at Rest | -1.1 percent oxygen (%) | Standard Error 0.59 |
| GBT440 600 mg Dose | Evaluate the Effect of GBT440 on Oxygen Saturation Using Pulse Oximetry at Rest | 0.3 percent oxygen (%) | Standard Error 0.77 |
| GBT440 900mg Dose | Evaluate the Effect of GBT440 on Oxygen Saturation Using Pulse Oximetry at Rest | 0.4 percent oxygen (%) | Standard Error 0.76 |
| GBT440 1500mg Dose | Evaluate the Effect of GBT440 on Oxygen Saturation Using Pulse Oximetry at Rest | 0.9 percent oxygen (%) | Standard Error 0.57 |
Secondary
Pharmacokinetic Profile of GBT440 Including Apparent Terminal Half Life
Time frame: 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
Population: Complete PK data were not analyzable for any participant.
Secondary
Pharmacokinetic Profile of GBT440 Including Maximum Concentration
Time frame: 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
Population: Complete PK data was not analyzable for any participant.
Secondary
Pharmacokinetic Profile of GBT440 Including Minimum Concentration
Time frame: 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
Population: Per protocol, analysis was to be conducted on complete PK analysis population; insufficient number of samples collected for pre-specified analysis.