4-Week Safety Study in Subjects with Neutrophilic Asthma
Effect of treatment with navarixin (MK-7123, SCH 527123) on sputum neutrophils and asthma symptoms
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
37
Navarixin 30 mg capsule to be taken by mouth once daily in the morning for 4 weeks.
Placebo capsule to match navarixin to be taken by mouth once daily in the morning for 4 weeks.
Participant choice of short-acting beta-2 agonist (salbutamol/albuterol), anticholinergic, or combination medication as needed for asthma symptoms
Number of Participants Who Maintained an Absolute Peripheral Blood Neutrophil Count >=1500/µL
Peripheral blood neutrophil counts were performed on Day 2 and Weeks 1, 2, 3, and 4 of the treatment period
Time frame: Up to 4 weeks
Mean Change From Baseline in Sputum Absolute Neutrophil Count
Induced sputum samples were obtained at Baseline and at Weeks 2 and 4 of the treatment period. Samples were collected before study drug administration using the nebulizer method and sent to a central laboratory for analysis. An average was taken over all post-baseline samples collected no later than one day after the last dose of study drug.
Time frame: Baseline and while on study drug (up to 4 weeks)
Mean Change From Baseline in Total Asthma Symptom Score
Total Asthma Symptom Score is the sum of individual symptoms of wheezing, coughing, and dyspnea assessed twice daily (morning and evening) and is recorded on a comment diary card. Each of the symptoms receives a daily score from 0 (none) to 3 (severe), averaged over the two daily assessments. The total score ranges from 0 to 9, with a lower score indicating less severe asthma symptoms.
Time frame: Baseline and Weeks 1, 2, 3, and 4
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1)
Spirometry was used to measure post-bronchodilator FEV1 at Baseline and before study drug administration at Weeks 1, 2, 3, and 4. Participants received 4 puffs of bronchodilator (salbutamol hydrofluoroalkane or equivalent) at 30-second intervals and spirometry was performed 30 minutes later. The mean change from baseline is based on the average change over all post-baseline assessments.
Time frame: Baseline and up to 4 weeks
Change From Baseline in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ[S])
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The AQLQ\[S\] was administered at Baseline and at Weeks 2 and 4. The assessment consists of a 32-item questionnaire covering 4 domains: symptoms, emotional functioning, impact of environmental stimuli, and activity limitation. Each item receives a score from 1 (worst, or most affected) to 7 (not at all affected). The score is the mean across all items, and ranges from 1 to 7. The mean change from baseline is based on the average change over all post-baseline assessments.
Time frame: Baseline and up to 4 weeks
Number of Participants With an Adverse Event (AE)
An AE is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. AEs may include the onset of new illness and the exacerbation of pre-existing conditions.
Time frame: Up to 5 weeks
Number of Participants With an Electrocardiogram Adverse Event
The endpoint measured was any electrocardiogram abnormality that was reported as an AE. An AE is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. AEs may include the onset of new illness and the exacerbation of pre-existing conditions.
Time frame: Week 4
Number of Participants With a Laboratory Adverse Event
The endpoint measured was any laboratory (hematology, blood chemistry, or urinalysis) abnormality that was reported as an AE. An AE is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. AEs may include the onset of new illness and the exacerbation of pre-existing conditions.
Time frame: Up to 5 weeks
Number of Participants Who Discontinued the Study Because of an Adverse Event
An AE is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. AEs may include the onset of new illness and the exacerbation of pre-existing conditions.
Time frame: Up to 5 weeks
Number of Participants Who Discontinued Treatment Because of an Adverse Event or a Protocol-defined Clinical Event
An AE is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. AEs may include the onset of new illness and the exacerbation of pre-existing conditions. A protocol-defined clinical event is an asthma exacerbation requiring addition of or increase in systemic steroids, as determined by the investigator.
Time frame: Up to 4 weeks
Maximum Plasma Concentration of Navarixin (Cmax)
Plasma samples were to be collected at baseline and up to 24 hours after dosing with navarixin at Weeks 1, 2, 3, and 4
Time frame: Week 1, 2, 3, and 4