Hypoxemia, Idiopathic Pulmonary Fibrosis
Conditions
Keywords
Idiopathic pulmonary fibrosis, hypoxemia, oxygen
Brief summary
This is an open label study in which eligible IPF subjects who are using supplemental oxygen at rest will receive GBT440 orally daily.
Interventions
DRUGGBT440
GBT440: Capsules which contain GBT440 drug substance in Swedish orange
Sponsors
Global Blood Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Documented diagnosis of IPF. * Receiving supplemental oxygen for use at rest. * Weight ≥ 40 kg. * Male or female of child bearing potential willing and able to use highly effective methods of contraception from study start to 30 days after the last dose of study drug.
Exclusion criteria
* FEV1/FVC \< 70% * History of other interstitial lung diseases. * Subject plans to begin or has commenced pulmonary rehabilitation within 30 days of screening. * Corticosteroid (\> 10 mg per day of prednisone or an equivalent) administered for 7 days or longer, within 30 days of screening. * 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). * Female who is breast-feeding or pregnant * Current smoker or history of smoking within 3 months from screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Oxygen Saturation at End of Treatment Period Compared to Baseline | Days 1 to 90 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Effect of GBT440 on Resting and Post-exercise Alveolar-arterial O2 Tension Difference [P(A-a) O2] at End of Treatment Period Compared to Baseline | Days 1 to 90 | — |
| Evaluate the Effect of GBT440 on Performance of the 6MWT | Days 1 to 90 | — |
| Evaluate the Effect of GBT440 on IPF Related Symptoms Using Patient Related Outcomes | Days 1 to 90 | — |
| Change in Supplemental Oxygen Requirement at End of Treatment Period Compared to Baseline | Days 1 to 90 | — |
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Days 1 to 90 | — |
| Pharmacokinetic Parameters of GBT440 in Plasma and Whole Blood (Minimum Concentration (Cmin)) | Day 1 (15 mins post-dose and 2-4h post-dose), Day 15 (pre-dose), Day 30 (pre-dose), Day 60 (pre-dose and 2-4h post-dose), Day 90 (pre-dose), Day 105 (during study visit), and Day 120 (during study visit) | PK parameters of GBT440 administered daily orally for 90 days in plasma and whole blood, including but not limited to, minimum concentration (Cmin), at steady state. |
| Evaluate Pulmonary Function Using Pulmonary Function Tests (FVC and DLco) | Days 1 to 90 | Spirometry measurements will include forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLco). |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GBT440 900 mg Dose Part A, 900 mg daily dose
GBT440: Capsules which contain GBT440 drug substance in Swedish orange | 11 |
| GBT440 1500 mg Dose Part B, 1500 mg daily dose
GBT440: Capsules which contain GBT440 drug substance in Swedish orange | 3 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Sponsor stopped study. | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | GBT440 900 mg Dose | GBT440 1500 mg Dose | Total |
|---|---|---|---|
| Age, Continuous | 69.0 years | 72.0 years | 70.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 3 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 10 Participants | 3 Participants | 13 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 10 Participants | 2 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 3 |
| other Total, other adverse events | 11 / 11 | 3 / 3 |
| serious Total, serious adverse events | 3 / 11 | 2 / 3 |
Outcome results
Primary
Change in Oxygen Saturation at End of Treatment Period Compared to Baseline
Time frame: Days 1 to 90
Population: Since study was stopped prematurely, complete data for all participants were not analyzable so no efficacy results are presented.
Secondary
Change in Supplemental Oxygen Requirement at End of Treatment Period Compared to Baseline
Time frame: Days 1 to 90
Population: Since study was stopped prematurely, complete data for all participants were not analyzable so no efficacy results are presented.
Secondary
Evaluate Pulmonary Function Using Pulmonary Function Tests (FVC and DLco)
Spirometry measurements will include forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLco).
Time frame: Days 1 to 90
Population: Since study was stopped prematurely, complete data for all participants were not analyzable so no efficacy results are presented.
Secondary
Evaluate the Effect of GBT440 on IPF Related Symptoms Using Patient Related Outcomes
Time frame: Days 1 to 90
Population: Since study was stopped prematurely, complete data for all participants were not analyzable so no efficacy results are presented.
Secondary
Evaluate the Effect of GBT440 on Performance of the 6MWT
Time frame: Days 1 to 90
Population: Since study was stopped prematurely, complete data for all participants were not analyzable so no efficacy results are presented.
Secondary
Evaluate the Effect of GBT440 on Resting and Post-exercise Alveolar-arterial O2 Tension Difference [P(A-a) O2] at End of Treatment Period Compared to Baseline
Time frame: Days 1 to 90
Population: Since study was stopped prematurely, complete data for all participants were not analyzable so no efficacy results are presented.
Secondary
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Time frame: Days 1 to 90
Population: Participant had at least one dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GBT440 900 mg Dose | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | 11 Participants |
| GBT440 1500 mg Dose | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | 3 Participants |
Secondary
Pharmacokinetic Parameters of GBT440 in Plasma and Whole Blood (Minimum Concentration (Cmin))
PK parameters of GBT440 administered daily orally for 90 days in plasma and whole blood, including but not limited to, minimum concentration (Cmin), at steady state.
Time frame: Day 1 (15 mins post-dose and 2-4h post-dose), Day 15 (pre-dose), Day 30 (pre-dose), Day 60 (pre-dose and 2-4h post-dose), Day 90 (pre-dose), Day 105 (during study visit), and Day 120 (during study visit)
Population: Complete PK data were not analyzable for any participant.