Cystic Fibrosis
Conditions
Brief summary
This phase IV, multicenter, randomized, open-label, two-period crossover study will evaluate the comparable efficacy and safety of Pulmozyme (dornase alfa) delivered by the eRapid nebulizer system in patients with cystic fibrosis. Patients who have been receiving Pulmozyme once daily chronically for at least 6 months will continue to receive Pulmozyme once daily for a run-in period of 2 weeks using the Pari LC Plus nebulizer. Patients will then be randomized to receive in a crossover design Pulmozyme once daily for two treatment periods of 2 weeks each using either the Pari LC Plus or the eRapid nebulizer. Anticipated time on study treatment is 6 weeks.
Interventions
DRUGdornase alfa [Pulmozyme®]
Inhaled once daily by Pari eRapid nebulizer.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female patients, \>/= 6 years of age * Confirmed diagnosis of cystic fibrosis (CF) * Receiving Pulmozyme once daily chronically for treatment of CF for at least 6 months prior to screening * Percent predicted FEV1 \>/= 40% at screening based on the Wang (males \< 18 years, females \< 16 years) or Hankinson (males \>/= 18 years, females \>/= 16 years) standardized equations * Able to reproducibly perform spirometry testing and comply with study assessments
Exclusion criteria
* An acute respiratory infection or pulmonary exacerbation within 4 weeks prior to randomization * Initiation of any new chronic therapy (e.g. inhaled corticosteroids, inhaled oral antibiotics, high-dose ibuprofen, hypertonic saline, ivacaftor) for respiratory disease within 4 weeks prior to randomization * Changes in chest physiotherapy schedule within 4 weeks prior to randomization * Hospitalization within 4 weeks prior to randomization * Planned hospitalization during the 6-week study * History of organ transplantation * Participation in an investigational drug or device study within 30 day prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stability of Lung Function: Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) | At the end of each 2-week treatment period | Spirometry was performed according to American Thoracic Society standards. FEV1 is the amount of air that is forced out of the lungs in one second and was measured at the end of each 2-week treatment period. The percent predicted FEV1 was calculated as: Percent predicted FEV1 =FEV1 (L) / Predicted FEV1 (L) ×100. |
| Safety: Number of Participants With Adverse Events During Each Treatment Period | 4 Weeks | An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. |
Countries
United States
Participant flow
Recruitment details
99 patients were enrolled. 96 unique patients entered the run-in period including 3 patients who entered the run-in period twice.
Pre-assignment details
Patients received dornase alfa (Pulmozyme®) by LC Plus nebulizer in the 2-week run-in period prior to randomization. A total of 86 unique patients were randomized in the study in 87 randomization events. Of the randomized patients, 85 patients completed the study in two treatment sequences.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants received dornase alfa (Pulmozyme) inhaled once daily by the Pari eRapid nebulizer or the Pari LC Plus jet nebulizer for 2 weeks in Treatment Period 1 then crossed over to use the other nebulizer in Treatment Period 2 for 2 weeks. | 85 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 | Randomized in Error | 0 | 2 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 13.6 years STANDARD_DEVIATION 6.92 |
| Sex: Female, Male Female | 43 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 85 | 0 / 85 |
| serious Total, serious adverse events | 0 / 85 | 0 / 85 |
Outcome results
Primary
Safety: Number of Participants With Adverse Events During Each Treatment Period
An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events.
Time frame: 4 Weeks
Population: Safety population included all randomized participants who received treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| eRapid Nebulizer | Safety: Number of Participants With Adverse Events During Each Treatment Period | 18 participants |
| Jet Nebulizer | Safety: Number of Participants With Adverse Events During Each Treatment Period | 24 participants |
Primary
Stability of Lung Function: Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)
Spirometry was performed according to American Thoracic Society standards. FEV1 is the amount of air that is forced out of the lungs in one second and was measured at the end of each 2-week treatment period. The percent predicted FEV1 was calculated as: Percent predicted FEV1 =FEV1 (L) / Predicted FEV1 (L) ×100.
Time frame: At the end of each 2-week treatment period
Population: Modified Intent-to-Treat (mITT) population included all randomized participants with baseline and endpoint FEV1 values for both treatment periods.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| eRapid Nebulizer | Stability of Lung Function: Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) | 98.1 percent predicted | Standard Deviation 22.1 |
| Jet Nebulizer | Stability of Lung Function: Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) | 97.2 percent predicted | Standard Deviation 20.7 |
90% CI: [99.5, 102.3]