Trial Outcomes & Findings for Neutrophilic Asthma Study With Navarixin (MK-7123, SCH 527123) (MK-7123-017)(COMPLETED) (NCT NCT00632502)

NCT ID: NCT00632502

Last Updated: 2019-01-02

Results Overview

Peripheral blood neutrophil counts were performed on Day 2 and Weeks 1, 2, 3, and 4 of the treatment period

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 37 participants
• Primary outcome timeframe: Up to 4 weeks
• Results posted on: 2019-01-02

Participant Flow

Participants were considered to complete the study if they completed the follow-up visit, whether or not they completed treatment.

Participant milestones

Measure	Navarixin Navarixin 30 mg capsule to be taken by mouth once daily for 4 weeks	Placebo Placebo capsule to be taken by mouth once daily for 4 weeks
Overall Study STARTED	25	12
Overall Study Treated	22	12
Overall Study Completed Treatment	19	9
Overall Study COMPLETED	22	11
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Measure	Navarixin Navarixin 30 mg capsule to be taken by mouth once daily for 4 weeks	Placebo Placebo capsule to be taken by mouth once daily for 4 weeks
Overall Study Adverse Event	0	1
Overall Study Randomized not treated	3	0

Baseline Characteristics

Neutrophilic Asthma Study With Navarixin (MK-7123, SCH 527123) (MK-7123-017)(COMPLETED)

Baseline characteristics by cohort

Measure	Navarixin n=22 Participants Navarixin 30 mg capsule to be taken by mouth once daily for 4 weeks	Placebo n=12 Participants Placebo capsule to be taken by mouth once daily for 4 weeks	Total n=34 Participants Total of all reporting groups
Age, Continuous	48.7 Years STANDARD_DEVIATION 10.6 • n=5 Participants	53.9 Years STANDARD_DEVIATION 6.8 • n=7 Participants	50.6 Years STANDARD_DEVIATION 9.6 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	7 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 4 weeks

Population: The analysis population included all participants who received at least one dose of study drug

Peripheral blood neutrophil counts were performed on Day 2 and Weeks 1, 2, 3, and 4 of the treatment period

Outcome measures

Measure	Navarixin n=22 Participants Navarixin 30 mg capsule to be taken by mouth once daily for 4 weeks	Placebo n=12 Participants Placebo capsule to be taken by mouth once daily for 4 weeks
Number of Participants Who Maintained an Absolute Peripheral Blood Neutrophil Count >=1500/µL	20 Number of participants	12 Number of participants

SECONDARY outcome

Timeframe: Baseline and while on study drug (up to 4 weeks)

Population: The analysis population included all randomized participants who received at least one dose of study drug and had sputum absolute neutrophil counts at Baseline or Week 4

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.

Outcome measures

Measure	Navarixin n=18 Participants Navarixin 30 mg capsule to be taken by mouth once daily for 4 weeks	Placebo n=11 Participants Placebo capsule to be taken by mouth once daily for 4 weeks
Mean Change From Baseline in Sputum Absolute Neutrophil Count Baseline sputum absolute neutrophil count	3.275 Neutrophil count X10^9/L Standard Deviation 3.995	3.408 Neutrophil count X10^9/L Standard Deviation 2.973
Mean Change From Baseline in Sputum Absolute Neutrophil Count Change from baseline at up to 4 weeks	-0.270 Neutrophil count X10^9/L Standard Deviation 6.673	0.680 Neutrophil count X10^9/L Standard Deviation 2.249

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 3, and 4

Population: The analysis population included all randomized participants who received at least one dose of study drug and had Asthma Symptom Scores evaluated at the time points reported

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.

Outcome measures

Measure	Navarixin n=21 Participants Navarixin 30 mg capsule to be taken by mouth once daily for 4 weeks	Placebo n=12 Participants Placebo capsule to be taken by mouth once daily for 4 weeks
Mean Change From Baseline in Total Asthma Symptom Score Baseline Total Asthma Symptom Score (n=21, 12)	2.47 Score on a scale Standard Deviation 1.83	2.40 Score on a scale Standard Deviation 1.30
Mean Change From Baseline in Total Asthma Symptom Score Change at 1 week (n=21, 12)	-0.07 Score on a scale Standard Deviation 1.01	0.05 Score on a scale Standard Deviation 0.78
Mean Change From Baseline in Total Asthma Symptom Score Change at 2 weeks (n=20, 12)	-0.25 Score on a scale Standard Deviation 1.50	0.19 Score on a scale Standard Deviation 1.14
Mean Change From Baseline in Total Asthma Symptom Score Change at 3 weeks (n=19, 12)	-0.19 Score on a scale Standard Deviation 1.56	0.04 Score on a scale Standard Deviation 1.30
Mean Change From Baseline in Total Asthma Symptom Score Change at 4 weeks (n=18, 9)	-0.00 Score on a scale Standard Deviation 1.62	-0.26 Score on a scale Standard Deviation 2.06

SECONDARY outcome

Timeframe: Baseline and up to 4 weeks

Population: The analysis population included all randomized participants who received at least one dose of study drug and had endpoint assessment at Baseline or at any post-baseline visit

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.

Outcome measures

Measure	Navarixin n=22 Participants Navarixin 30 mg capsule to be taken by mouth once daily for 4 weeks	Placebo n=12 Participants Placebo capsule to be taken by mouth once daily for 4 weeks
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Baseline FEV1	2.197 Liters Standard Deviation 0.948	1.851 Liters Standard Deviation 0.469
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1) Average change from baseline at up to 4 weeks	-0.099 Liters Standard Deviation 0.315	-0.094 Liters Standard Deviation 0.106

SECONDARY outcome

Timeframe: Baseline and up to 4 weeks

Population: The analysis population included all randomized participants who received at least one dose of study drug and had endpoint evaluation at Baseline or at any post-baseline visit

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.

Outcome measures

Measure	Navarixin n=21 Participants Navarixin 30 mg capsule to be taken by mouth once daily for 4 weeks	Placebo n=12 Participants Placebo capsule to be taken by mouth once daily for 4 weeks
Change From Baseline in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ[S]) Baseline AQLQ[S] Score	4.822 Score on a scale Standard Deviation 1.568	4.897 Score on a scale Standard Deviation 1.128
Change From Baseline in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ[S]) Average change from baseline at up to 4 weeks	0.165 Score on a scale Standard Deviation 0.901	0.119 Score on a scale Standard Deviation 0.936

SECONDARY outcome

Timeframe: Up to 5 weeks

Population: The analysis population included all participants who received at least one dose of study drug

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.

Outcome measures

Measure	Navarixin n=22 Participants Navarixin 30 mg capsule to be taken by mouth once daily for 4 weeks	Placebo n=12 Participants Placebo capsule to be taken by mouth once daily for 4 weeks
Number of Participants With an Adverse Event (AE)	13 Participants	8 Participants

SECONDARY outcome

Timeframe: Week 4

Population: The analysis population included all participants who received at least one dose of study drug

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.

Outcome measures

Measure	Navarixin n=22 Participants Navarixin 30 mg capsule to be taken by mouth once daily for 4 weeks	Placebo n=12 Participants Placebo capsule to be taken by mouth once daily for 4 weeks
Number of Participants With an Electrocardiogram Adverse Event	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 5 weeks

Population: The analysis population included all participants who received at least one dose of study drug

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.

Outcome measures

Measure	Navarixin n=22 Participants Navarixin 30 mg capsule to be taken by mouth once daily for 4 weeks	Placebo n=12 Participants Placebo capsule to be taken by mouth once daily for 4 weeks
Number of Participants With a Laboratory Adverse Event	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 5 weeks

Population: The analysis population included all participants who received at least one dose of study drug

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.

Outcome measures

Measure	Navarixin n=22 Participants Navarixin 30 mg capsule to be taken by mouth once daily for 4 weeks	Placebo n=12 Participants Placebo capsule to be taken by mouth once daily for 4 weeks
Number of Participants Who Discontinued the Study Because of an Adverse Event	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 4 weeks

Population: The analysis population included all participants who received at least one dose of study drug

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.

Outcome measures

Measure	Navarixin n=22 Participants Navarixin 30 mg capsule to be taken by mouth once daily for 4 weeks	Placebo n=12 Participants Placebo capsule to be taken by mouth once daily for 4 weeks
Number of Participants Who Discontinued Treatment Because of an Adverse Event or a Protocol-defined Clinical Event Adverse event	2 Participants	2 Participants
Number of Participants Who Discontinued Treatment Because of an Adverse Event or a Protocol-defined Clinical Event Protocol-defined clinical event	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Week 1, 2, 3, and 4

Population: The analysis population was to include all participants who received at least one dose of navarixin and had navarixin plasma concentrations available for endpoint evaluation. The planned outcome measure was not evaluated.

Plasma samples were to be collected at baseline and up to 24 hours after dosing with navarixin at Weeks 1, 2, 3, and 4

Outcome measures

Outcome data not reported

Adverse Events

Navarixin

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Navarixin n=22 participants at risk Navarixin 30 mg capsule to be taken by mouth once daily for 4 weeks	Placebo n=12 participants at risk Placebo capsule to be taken by mouth once daily for 4 weeks
Eye disorders Conjunctivitis	0.00% 0/22 • Up to 5 weeks	8.3% 1/12 • Number of events 1 • Up to 5 weeks
Gastrointestinal disorders Abdominal pain upper	9.1% 2/22 • Number of events 2 • Up to 5 weeks	0.00% 0/12 • Up to 5 weeks
Gastrointestinal disorders Diarrhoea	0.00% 0/22 • Up to 5 weeks	8.3% 1/12 • Number of events 2 • Up to 5 weeks
Gastrointestinal disorders Nausea	9.1% 2/22 • Number of events 2 • Up to 5 weeks	0.00% 0/12 • Up to 5 weeks
Infections and infestations Bacterial infection	0.00% 0/22 • Up to 5 weeks	8.3% 1/12 • Number of events 1 • Up to 5 weeks
Infections and infestations Furuncle	0.00% 0/22 • Up to 5 weeks	8.3% 1/12 • Number of events 1 • Up to 5 weeks
Infections and infestations Influenza	9.1% 2/22 • Number of events 2 • Up to 5 weeks	0.00% 0/12 • Up to 5 weeks
Infections and infestations Lower respiratory tract infection	0.00% 0/22 • Up to 5 weeks	8.3% 1/12 • Number of events 1 • Up to 5 weeks
Infections and infestations Nasopharyngitis	18.2% 4/22 • Number of events 4 • Up to 5 weeks	8.3% 1/12 • Number of events 1 • Up to 5 weeks
Infections and infestations Upper respiratory tract infection	4.5% 1/22 • Number of events 1 • Up to 5 weeks	8.3% 1/12 • Number of events 1 • Up to 5 weeks
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/22 • Up to 5 weeks	8.3% 1/12 • Number of events 1 • Up to 5 weeks
Nervous system disorders Headache	13.6% 3/22 • Number of events 3 • Up to 5 weeks	33.3% 4/12 • Number of events 7 • Up to 5 weeks
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/22 • Up to 5 weeks	8.3% 1/12 • Number of events 1 • Up to 5 weeks
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/22 • Up to 5 weeks	8.3% 1/12 • Number of events 1 • Up to 5 weeks
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.1% 2/22 • Number of events 2 • Up to 5 weeks	0.00% 0/12 • Up to 5 weeks

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee The investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the study. The sponsor shall have the right to review and comment with respect to publications, abstracts, slides, and manuscripts and the right to review and comment on the data analysis and presentation.
• Publication restrictions are in place

Restriction type: OTHER