Trial Outcomes & Findings for Long-Term Study of the Effects of Navarixin (SCH 527123, MK-7123) in Participants With Moderate to Severe COPD (MK-7123-019) (NCT NCT01006616)

Last Updated: 2019-01-02

Results Overview

FEV1, as measured in liters by spirometry, is the amount of air expired in 1 second. Participants were assessed for post-bronchodilator FEV1 30 minutes after bronchodilator administration (4 puffs of albuterol/salbutamol or equivalent separated by 30-second intervals) (reversibility test) at Baseline and Week 26.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

616 participants

Primary outcome timeframe

Baseline and Week 26

Results posted on

2019-01-02

Participant Flow

Participant milestones

Participant milestones
Measure	Navarixin 10 mg Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally once daily (QD) for up to 2 years	Navarixin 30 mg Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Period 1 (6 Months) STARTED	152	156	153	155
Period 1 (6 Months) Treated	152	156	152	154
Period 1 (6 Months) COMPLETED	126	102	102	128
Period 1 (6 Months) NOT COMPLETED	26	54	51	27
Period 2 (18 Months) STARTED	75	63	55	82
Period 2 (18 Months) Treated	75	63	55	82
Period 2 (18 Months) COMPLETED	0	0	0	0
Period 2 (18 Months) NOT COMPLETED	75	63	55	82

Reasons for withdrawal

Reasons for withdrawal
Measure	Navarixin 10 mg Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally once daily (QD) for up to 2 years	Navarixin 30 mg Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Period 1 (6 Months) Adverse Event	10	31	37	9
Period 1 (6 Months) Lack of Efficacy	3	4	0	4
Period 1 (6 Months) Lost to Follow-up	0	0	1	0
Period 1 (6 Months) Withdrew, Reason Unrelated to Treatment	6	5	2	3
Period 1 (6 Months) Withdrew, Reason Related to Treatment	0	3	1	2
Period 1 (6 Months) Withdrawal by Subject	2	2	2	0
Period 1 (6 Months) Did Not Meet Protocol Eligibility	5	7	5	5
Period 1 (6 Months) Noncompliance With Protocol	0	2	2	3
Period 1 (6 Months) Not Treated	0	0	1	1
Period 2 (18 Months) Adverse Event	6	6	6	4
Period 2 (18 Months) Lack of Efficacy	0	0	1	2
Period 2 (18 Months) Lost to Follow-up	2	0	0	0
Period 2 (18 Months) Withdrew, Reason Unrelated to Treatment	3	0	3	2
Period 2 (18 Months) Withdrew, Reason Related to Treatment	0	6	1	2
Period 2 (18 Months) Withdrawal by Subject	1	4	0	1
Period 2 (18 Months) Noncompliance With Protocol	0	1	0	1
Period 2 (18 Months) Study Terminated	63	46	44	70

Baseline Characteristics

Long-Term Study of the Effects of Navarixin (SCH 527123, MK-7123) in Participants With Moderate to Severe COPD (MK-7123-019)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Navarixin 10 mg n=152 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=156 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=152 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=154 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years	Total n=614 Participants Total of all reporting groups
Age, Continuous	63.7 Years STANDARD_DEVIATION 6.9 • n=5 Participants	63.2 Years STANDARD_DEVIATION 7.4 • n=7 Participants	61.3 Years STANDARD_DEVIATION 7.5 • n=5 Participants	63.3 Years STANDARD_DEVIATION 7.2 • n=4 Participants	62.9 Years STANDARD_DEVIATION 7.3 • n=21 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	52 Participants n=7 Participants	50 Participants n=5 Participants	46 Participants n=4 Participants	176 Participants n=21 Participants
Sex: Female, Male Male	124 Participants n=5 Participants	104 Participants n=7 Participants	102 Participants n=5 Participants	108 Participants n=4 Participants	438 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline and Week 26

Population: The Full Analysis Set (FAS) population consisted of all participants who received at least one dose of study drug and had a Baseline and Week 26 assessment for post-bronchodilator FEV1.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=124 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=105 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=102 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=127 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Change From Baseline in Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (Period 1)	-0.009 Liters Standard Error 0.022	-0.068 Liters Standard Error 0.023	0.028 Liters Standard Error 0.024	-0.039 Liters Standard Error 0.022

PRIMARY outcome

Timeframe: Up to 104 weeks

Population: The All Subjects as Treated (ASaT) population consisted of all participants who received at least one dose of study drug. The study was terminated during Period 2; no data were analyzed for this endpoint for up to 52 and up to 104 weeks.

The percentage of participants who experienced an AE related to an ANC of less than 1.5x10\^9 cells/L at one or more visits during the first 26 weeks, the first 52 weeks and the first 104 weeks was to be calculated.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=152 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=156 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=152 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=154 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Percentage of Participants With an Adverse Event (AE) Related to a Blood Absolute Neutrophil Count (ANC) of Less Than 1.5x10^9 Cells/L Up to Week 52 (n=0, 0, 0, 0)	NA Percentage of Participants Study terminated; data not collected.	NA Percentage of Participants Study terminated; data not collected.	NA Percentage of Participants Study terminated; data not collected.	NA Percentage of Participants Study terminated; data not collected.
Percentage of Participants With an Adverse Event (AE) Related to a Blood Absolute Neutrophil Count (ANC) of Less Than 1.5x10^9 Cells/L Up to Week 26 (n=152, 156, 152,154)	3.3 Percentage of Participants	12.8 Percentage of Participants	20.4 Percentage of Participants	0.6 Percentage of Participants
Percentage of Participants With an Adverse Event (AE) Related to a Blood Absolute Neutrophil Count (ANC) of Less Than 1.5x10^9 Cells/L Up to Week 104 (n=0, 0, 0, 0)	NA Percentage of Participants Study terminated; data not collected.	NA Percentage of Participants Study terminated; data not collected.	NA Percentage of Participants Study terminated; data not collected.	NA Percentage of Participants Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline and Week 52, Week 104

Population: The FAS population consisted of all participants who received at least one dose of study drug and had a Baseline and Week 52 or Week 104 assessment for post-bronchodilator FEV1 in Period 2. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

FEV1, as measured in liters by spirometry, is the amount of air expired in 1 second. Participants were to be assessed for post-bronchodilator FEV1 30 minutes after bronchodilator administration (4 puffs of albuterol/salbutamol or equivalent separated by 30-second intervals) (reversibility test) at Baseline, Week 52 and Week 104.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=66 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=47 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=44 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=65 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Change From Baseline in Post-bronchodilator FEV1 (Period 2) Week 104 (n=0, 0, 0, 0)	NA Liters Standard Error NA Study terminated; data not collected.	NA Liters Standard Error NA Study terminated; data not collected.	NA Liters Standard Error NA Study terminated; data not collected.	NA Liters Standard Error NA Study terminated; data not collected.
Change From Baseline in Post-bronchodilator FEV1 (Period 2) Week 52 (n=66, 47, 44, 65)	-0.047 Liters Standard Error 0.027	-0.084 Liters Standard Error 0.031	0.028 Liters Standard Error 0.032	-0.031 Liters Standard Error 0.027

SECONDARY outcome

Timeframe: Up to 26 , 52 and 104 weeks

Population: The FAS population consisted of all participants who received at least one dose of study drug and had a Week 26, Week 52 or Week 104 assessment for COPD exacerbation. The study was terminated during Period 2; no data were collected for this endpoint for up to 104 weeks.

COPD exacerbation is defined as any deterioration of symptoms that leads to an increase in bronchodilator use on 2 or more consecutive days, or administration (at investigator's discretion) of antibiotics and/or systemic corticosteroids (above participant's usual dose), or an unscheduled COPD-related doctor visit, hospitalization or emergency room treatment. The numbers of participants who experienced at least one moderate to severe COPD exacerbation during the first 26 weeks, the first 52 weeks and the first 104 weeks of treatment were to be summarized.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=152 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=156 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=152 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=154 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Number of Participants With a Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Up to Week 26 (n=152, 156, 152, 154)	40 Participants	50 Participants	45 Participants	48 Participants
Number of Participants With a Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Up to Week 52 (n=152, 156, 152, 154)	50 Participants	58 Participants	51 Participants	53 Participants
Number of Participants With a Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Up to Week 104 (n=0, 0, 0, 0)	NA Participants Study terminated; data not collected.	NA Participants Study terminated; data not collected.	NA Participants Study terminated; data not collected.	NA Participants Study terminated; data not collected.

SECONDARY outcome

Timeframe: Up to 26, 52 and 104 weeks

Population: The FAS population consisted of all participants who received at least one dose of study drug and had a Baseline and Week 26, Week 52 or Week 104 assessment for COPD exacerbation. The study was terminated during Period 2; no data were collected for this endpoint for up to 104 weeks.

COPD exacerbation is defined as any deterioration of symptoms that leads to an increase in bronchodilator use on 2 or more consecutive days, or administration (at investigator's discretion) of antibiotics and/or systemic corticosteroids (above participant's usual dose), or an unscheduled COPD-related doctor visit, hospitalization or emergency room treatment. The percentages of participants who experienced at least one moderate to severe COPD exacerbation during the first 26 weeks, the first 52 weeks and the first 104 weeks of treatment were to be summarized.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=152 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=156 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=152 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=154 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Percentage of Participants With a Moderate to Severe COPD Exacerbation Up to Week 26 (n=152, 156, 152, 154)	26.3 Percentage of Participants	32.1 Percentage of Participants	29.6 Percentage of Participants	31.2 Percentage of Participants
Percentage of Participants With a Moderate to Severe COPD Exacerbation Up to Week 52 (n=152, 156, 152, 154)	32.9 Percentage of Participants	37.2 Percentage of Participants	33.6 Percentage of Participants	34.4 Percentage of Participants
Percentage of Participants With a Moderate to Severe COPD Exacerbation Up to Week 104 (n=0, 0, 0, 0)	NA Percentage of Participants Study terminated; data not collected.	NA Percentage of Participants Study terminated; data not collected.	NA Percentage of Participants Study terminated; data not collected.	NA Percentage of Participants Study terminated; data not collected.

SECONDARY outcome

Timeframe: At 26, 52 and 104 weeks

Population: The FAS population was to consist of all participants who received at least one dose of study drug and had a Baseline and Week 26, Week 52 or Week 104 assessment for total EXACT-PRO score. This analysis was not conducted if results for percentage of participants with moderate to severe COPD exacerbation suggested no need for further investigation.

The total score on the EXACT-PRO questionnaire is used to determine the frequency, severity, and duration of exacerbations of COPD. The 14-item EXACT-PRO questionnaire was to be completed by participants every evening to describe their experience of COPD during that day. Assessments were included for Breathlessness (5 items), Cough and Sputum (2 items), Chest Symptoms (3 items), and 4 additional items (Difficulty with Sputum, Tired or Weak, Sleep Disturbance, and Psychological State). Each item was measured on a 5- or 6-point scale. The total EXACT-PRO questionnaire score could range from 0 to 100, with a higher score indicating a more severe health state.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants at selected sites who received at least one dose of study drug and had a baseline and Week 26, Week 52 or Week 104 assessment for sputum neutrophil count. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

Induced sputum samples were to be obtained from participants via the nebulized method for analysis of absolute neutrophil counts at Week 26, Week 52 and Week 104. The reported Baseline least squares (LS) means and standard deviations (SDs) are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an analysis of variance (ANOVA) method using pooled SD values is the assumption that the SDs are similar across treatment groups.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=30 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=29 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=33 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=33 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Induced Sputum Absolute Neutrophil Counts Baseline (n=30, 29, 33, 33)	1.485 10^9 cells/L Standard Deviation 0.706	1.485 10^9 cells/L Standard Deviation 0.706	1.485 10^9 cells/L Standard Deviation 0.706	1.485 10^9 cells/L Standard Deviation 0.706
Induced Sputum Absolute Neutrophil Counts Week 26 (n=23, 13, 13, 17)	1.763 10^9 cells/L Standard Deviation 0.736	2.073 10^9 cells/L Standard Deviation 0.736	0.860 10^9 cells/L Standard Deviation 0.736	2.121 10^9 cells/L Standard Deviation 0.736
Induced Sputum Absolute Neutrophil Counts Week 52 (n=9, 8, 3, 3)	2.884 10^9 cells/L Standard Deviation 0.462	2.022 10^9 cells/L Standard Deviation 0.462	1.253 10^9 cells/L Standard Deviation 0.462	3.218 10^9 cells/L Standard Deviation 0.462
Induced Sputum Absolute Neutrophil Counts Week 104 (n=0, 0, 0, 0)	NA 10^9 cells/L Standard Deviation NA Study terminated; data not collected.	NA 10^9 cells/L Standard Deviation NA Study terminated; data not collected.	NA 10^9 cells/L Standard Deviation NA Study terminated; data not collected.	NA 10^9 cells/L Standard Deviation NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline and Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants who received at least one dose of study drug and had a Baseline and Week 26, Week 52 or Week 104 assessment for SGRQ-C score. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

The SGRQ-C consists of 40 items aggregated into 3 component scores: Symptoms (frequency/severity), Activity (limited by breathlessness), Impacts (social functioning, psychological disturbances), and a Total score. Each response to a question is assigned a weight. Component scores are calculated by summing the weights from all positive items in that component, dividing by the sum of weights for all items in that component, and multiplying this number by 100. Component scores could range from 0-100, with a higher component score indicating greater disease burden. The Total score is calculated by summing the weights to all the positive responses in each component, dividing by the sum of weights for all items in the questionnaire, and multiplying this number by 100. SGRQ-C Total scores could range from 0-100, with a higher SGRQ-C Total score indicating greater disease burden. Participants were to assess their COPD symptoms, activity and impact at Baseline, Week 26, Week 52, and Week 104.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=130 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=112 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=106 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=131 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Change From Baseline in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score Change at Week 26 (n=130, 112, 106, 131)	-2.65 Score on a Scale Standard Error 1.15	-2.28 Score on a Scale Standard Error 1.21	-4.63 Score on a Scale Standard Error 1.23	-1.60 Score on a Scale Standard Error 1.15
Change From Baseline in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score Change at Week 52 (n=62, 50, 45, 63)	-2.49 Score on a Scale Standard Error 1.58	-2.22 Score on a Scale Standard Error 1.73	-3.86 Score on a Scale Standard Error 1.80	-4.40 Score on a Scale Standard Error 1.57
Change From Baseline in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score Change at Week 104 (n=0, 0, 0, 0)	NA Score on a Scale Standard Error NA Study terminated; data not collected.	NA Score on a Scale Standard Error NA Study terminated; data not collected.	NA Score on a Scale Standard Error NA Study terminated; data not collected.	NA Score on a Scale Standard Error NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline and Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants at selected sites who received at least one dose of study drug and had a Baseline and Week 26, Week 52 or Week 104 assessment for 6-minute walk test. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

The 6-minute walk test measures the distance participants can walk quickly on a flat, hard surface in 6 minutes. The 6-minute walk test was to be conducted at Baseline, Week 26, Week 52 and Week 104.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=84 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=77 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=68 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=87 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test) Change at Week 26 (n=84, 77, 68, 87)	18.87 Meters Standard Error 6.55	-1.04 Meters Standard Error 6.79	2.06 Meters Standard Error 7.19	7.41 Meters Standard Error 6.45
Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test) Change at Week 52 (n=32, 25, 25, 30)	19.79 Meters Standard Error 11.50	-33.58 Meters Standard Error 12.74	0.93 Meters Standard Error 12.84	-15.37 Meters Standard Error 11.77
Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test) Change at Week 104 (n=0, 0, 0, 0)	NA Meters Standard Error NA Study terminated; data not collected.	NA Meters Standard Error NA Study terminated; data not collected.	NA Meters Standard Error NA Study terminated; data not collected.	NA Meters Standard Error NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline and Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants who received at least one dose of study drug and had a Baseline and Week 26, Week 52 or Week 104 assessment for pre-bronchodilator FEV1. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

FEV1, as measured in liters by spirometry, is the amount of air expired in 1 second. Pre-bronchodilator FEV1 was to be assessed immediately before bronchodilator administration at Baseline, Week 26, Week 52 and Week 104.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=124 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=104 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=103 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=126 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Change From Baseline in Pre-bronchodilator FEV1 Change at Week 26 (n=124, 104, 103 126)	-0.035 Liters Standard Error 0.021	-0.084 Liters Standard Error 0.022	0.008 Liters Standard Error 0.022	-0.054 Liters Standard Error 0.021
Change From Baseline in Pre-bronchodilator FEV1 Change at Week 52 (n=65, 47, 43, 67)	-0.049 Liters Standard Error 0.025	-0.084 Liters Standard Error 0.028	0.019 Liters Standard Error 0.029	-0.073 Liters Standard Error 0.025
Change From Baseline in Pre-bronchodilator FEV1 Change at Week 104 (n=0, 0, 0, 0)	NA Liters Standard Error NA Study terminated; data not collected.	NA Liters Standard Error NA Study terminated; data not collected.	NA Liters Standard Error NA Study terminated; data not collected.	NA Liters Standard Error NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline and Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants who received at least one dose of study drug and had a Baseline and Week 26, Week 52 or Week 104 assessment for FEF25%-75%. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

Mid-Breath Forced Expiratory Flow (FEF25%-75%), as measured in liters/minute by spirometry, is the rate at which participants breathe out air from 25 percent of their breath to 75 percent of their breath. FEF25%-75% was to be assessed at Baseline, Week 26, Week 52 and Week 104.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=124 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=105 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=102 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=127 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Change From Baseline in Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity (FEF25%-75%) Test Change at Week 26 (n=124, 105, 102, 127)	0.000 Liters/minute Standard Error 0.016	-0.053 Liters/minute Standard Error 0.017	0.028 Liters/minute Standard Error 0.017	-0.022 Liters/minute Standard Error 0.016
Change From Baseline in Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity (FEF25%-75%) Test Change at Week 52 (n=66, 47, 44, 65)	-0.008 Liters/minute Standard Error 0.020	-0.055 Liters/minute Standard Error 0.022	0.031 Liters/minute Standard Error 0.023	-0.018 Liters/minute Standard Error 0.020
Change From Baseline in Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity (FEF25%-75%) Test Change at Week 104 (n=0, 0, 0, 0)	NA Liters/minute Standard Error NA Study terminated; data not collected.	NA Liters/minute Standard Error NA Study terminated; data not collected.	NA Liters/minute Standard Error NA Study terminated; data not collected.	NA Liters/minute Standard Error NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline and Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants who received at least one dose of study drug and had a Baseline and Week 26, Week 52 or Week 104 assessment for post-bronchodilator FVC. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

FVC, as measured in liters by spirometry, is the amount of air forcibly exhaled from the lungs after taking the deepest breath possible. Post-bronchodilator FVC was to be assessed 30 minutes after bronchodilator administration (4 puffs of albuterol/salbutamol or equivalent separated by 30-second intervals) at Baseline, Week 26, Week 52 and Week 104.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=124 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=105 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=102 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=127 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) Change at Week 26 (n=124, 105, 102, 127)	-0.020 Liters Standard Error 0.040	-0.089 Liters Standard Error 0.042	-0.009 Liters Standard Error 0.043	-0.086 Liters Standard Error 0.039
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) Change at Week 52 (n=66, 47, 44, 65)	-0.106 Liters Standard Error 0.050	-0.077 Liters Standard Error 0.057	0.039 Liters Standard Error 0.059	-0.057 Liters Standard Error 0.050
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) Change at Week 104 (n=0, 0, 0, 0)	NA Liters Standard Error NA Study terminated; data not collected.	NA Liters Standard Error NA Study terminated; data not collected.	NA Liters Standard Error NA Study terminated; data not collected.	NA Liters Standard Error NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline and Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants who received at least one dose of study drug and had a Baseline and Week 26, Week 52 or Week 104 assessment for FRC. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

FRC, as measured in liters by body plethysmography, is the volume of air present in the lungs at the end of passive expiration. FRC was to be assessed after post-bronchodilator spirometry tests were performed at Baseline, Week 26, Week 52 and Week 104.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=65 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=55 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=50 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=59 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Change From Baseline in Functional Residual Capacity (FRC) Change at Week 26 (n=65, 55, 50, 59)	0.15 Liters Standard Error 0.11	-0.11 Liters Standard Error 0.12	-0.07 Liters Standard Error 0.12	0.07 Liters Standard Error 0.11
Change From Baseline in Functional Residual Capacity (FRC) Change at Week 52 (n=24, 21, 18, 21)	0.21 Liters Standard Error 0.13	0.12 Liters Standard Error 0.14	0.10 Liters Standard Error 0.15	0.13 Liters Standard Error 0.14
Change From Baseline in Functional Residual Capacity (FRC) Change at Week 104 (n=0, 0, 0, 0)	NA Liters Standard Error NA Study terminated; data not collected.	NA Liters Standard Error NA Study terminated; data not collected.	NA Liters Standard Error NA Study terminated; data not collected.	NA Liters Standard Error NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline and Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants who received at least one dose of study drug and had a Baseline and Week 26, Week 52 or Week 104 assessment for TLC. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

TLC, as measured in liters by body plethysmography, is the most amount of air lungs can hold at the top of breathing in. TLC was to be assessed after post-bronchodilator spirometry tests were performed at Baseline, Week 26, Week 52 and Week 104.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=65 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=55 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=50 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=59 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Change From Baseline in Total Lung Capacity (TLC) Change at Week 26 (n=65, 55, 50, 59)	0.11 Liters Standard Error 0.11	-0.14 Liters Standard Error 0.12	-0.06 Liters Standard Error 0.12	0.03 Liters Standard Error 0.11
Change From Baseline in Total Lung Capacity (TLC) Change at Week 52 (n=24, 21, 18, 21)	0.15 Liters Standard Error 0.13	0.01 Liters Standard Error 0.14	0.13 Liters Standard Error 0.15	0.11 Liters Standard Error 0.14
Change From Baseline in Total Lung Capacity (TLC) Change at Week 104 (n=0, 0, 0, 0)	NA Liters Standard Error NA Study terminated; data not collected.	NA Liters Standard Error NA Study terminated; data not collected.	NA Liters Standard Error NA Study terminated; data not collected.	NA Liters Standard Error NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline and Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants who received at least one dose of study drug and had a Baseline and Week 26, Week 52 or Week 104 assessment for IC. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

IC, as measured in liters by body plethysmography, is the maximum amount of air inspired when taking a slow, full inspiration with no hesitation from a position of passive end-tidal expiration (i.e. FRC) to a position of maximal inspiration. IC was to be assessed after post-bronchodilator spirometry tests were performed at Baseline, Week 26, Week 52 and Week 104.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=66 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=55 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=50 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=60 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Change From Baseline in Inspiratory Capacity (IC) Change at Week 26 (n=66, 55, 50, 60)	-0.04 Liters Standard Error 0.05	-0.05 Liters Standard Error 0.06	0.01 Liters Standard Error 0.06	-0.05 Liters Standard Error 0.06
Change From Baseline in Inspiratory Capacity (IC) Change at Week 52 (n=24, 21, 18, 21)	-0.02 Liters Standard Error 0.08	-0.12 Liters Standard Error 0.09	0.04 Liters Standard Error 0.09	0.02 Liters Standard Error 0.09
Change From Baseline in Inspiratory Capacity (IC) Change at Week 104 (n=0, 0, 0, 0)	NA Liters Standard Error NA Study terminated; data not collected.	NA Liters Standard Error NA Study terminated; data not collected.	NA Liters Standard Error NA Study terminated; data not collected.	NA Liters Standard Error NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline and Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants who received at least one dose of study drug and had a Baseline and Week 26, Week 52 or Week 104 assessment for PEF. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

PEF, as measured in liters/minute with a peak flow meter, is the maximum speed of expiration. Participants were to perform at least 3 and up to 5 PEF measurements in the morning before taking study drug. PEF was to be assessed at Baseline, Week 26, Week 52 and Week 104.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=119 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=97 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=95 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=122 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Change From Baseline in Morning Peak Expiratory Flow (PEF) Change at Week 26 (n=119, 97, 95, 122)	-14.7 Liters/minute Standard Error 4.28	-20.5 Liters/minute Standard Error 4.50	-11.6 Liters/minute Standard Error 4.61	-21.8 Liters/minute Standard Error 4.26
Change From Baseline in Morning Peak Expiratory Flow (PEF) Change at Week 52 (n=61, 48, 43, 63)	-23.7 Liters/minute Standard Error 9.69	-22.9 Liters/minute Standard Error 10.88	-0.48 Liters/minute Standard Error 11.50	-26.2 Liters/minute Standard Error 9.54
Change From Baseline in Morning Peak Expiratory Flow (PEF) Change at Week 104 (n=0, 0, 0, 0)	NA Liters/minute Standard Error NA Study terminated; data not collected.	NA Liters/minute Standard Error NA Study terminated; data not collected.	NA Liters/minute Standard Error NA Study terminated; data not collected.	NA Liters/minute Standard Error NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline and Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants at selected sites who received at least one dose of study drug and had a Baseline and Week 26, Week 52 or Week 104 assessment for BODE index score. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

The BODE index is a composite score assessing COPD prognosis that consists of 4 variables that are individually scored: FEV1 percent predicted, 6-Minute Walk Test, Modified Medical Research Council (MMRC) dyspnea scale and body mass index (BMI). The FEV1 percent predicted was scored from ≥65% (0 points, less airway obstruction) to ≤35% (3 points, greater airway obstruction). The 6-Minute Walk Distance was scored from: ≥350 meters (0 points, good exercise capacity) to ≤149 meters (3 points, poor exercise capacity). The MMRC Dyspnea Scale was scored from: MMRC 0: Dyspneic on strenuous exercise (0 points) to MMRC 4: Cannot leave house; breathless on dressing/undressing (3 points). BMI was scored as: \>21 (0 points) and ≤21 (1 point). Variable scores were summed to produce a BODE index score. BODE index scores could range from 0 to 10, with a higher score correlating with an increased risk of COPD mortality. BODE index scores were to be assessed at Baseline, Week 26, Week 52 and Week 104.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=83 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=72 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=67 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=84 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Change From Baseline in Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Index Score Change at Week 26 (n=83, 72, 67, 84)	-0.35 Score on a Scale Standard Error 0.12	0.13 Score on a Scale Standard Error 0.13	-0.21 Score on a Scale Standard Error 0.13	0.07 Score on a Scale Standard Error 0.12
Change From Baseline in Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Index Score Change at Week 52 (n=31, 21, 23, 27)	-0.10 Score on a Scale Standard Error 0.21	-0.02 Score on a Scale Standard Error 0.25	0.09 Score on a Scale Standard Error 0.24	0.12 Score on a Scale Standard Error 0.22
Change From Baseline in Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Index Score Change at Week 104 (n=0, 0, 0, 0)	NA Score on a Scale Standard Error NA Study terminated; data not collected.	NA Score on a Scale Standard Error NA Study terminated; data not collected.	NA Score on a Scale Standard Error NA Study terminated; data not collected.	NA Score on a Scale Standard Error NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline and Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants who received at least one dose of study drug and had a Baseline and Week 26, Week 52 or Week 104 assessment for MMRC dyspnea score. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

The MMRC dyspnea scale is used to assess participant breathlessness. The MMRC dyspnea scale consists of five grades that describe almost the entire range of respiratory disability from none (Grade 0=Not troubled with breathlessness except with strenuous exercise) to almost complete incapacity (Grade 4=Too breathless to leave the house or breathless when dressing or undressing). MMRC dyspnea scores were to be assessed at Baseline, Week 26, Week 52 and Week 104.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=83 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=75 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=68 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=86 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Change From Baseline in Modified Medical Research Council (MMRC) Dyspnea Score Change at Week 26 (n=83, 75, 68, 86)	-0.34 Score on a Scale Standard Error 0.08	-0.02 Score on a Scale Standard Error 0.09	-0.24 Score on a Scale Standard Error 0.09	-0.07 Score on a Scale Standard Error 0.08
Change From Baseline in Modified Medical Research Council (MMRC) Dyspnea Score Change at Week 52 (n=33, 28, 25, 31)	-0.25 Score on a Scale Standard Error 0.15	0.05 Score on a Scale Standard Error 0.16	-0.09 Score on a Scale Standard Error 0.17	-0.07 Score on a Scale Standard Error 0.15
Change From Baseline in Modified Medical Research Council (MMRC) Dyspnea Score Change at Week 104 (n=0, 0, 0, 0)	NA Score on a Scale Standard Error NA Study terminated; data not collected.	NA Score on a Scale Standard Error NA Study terminated; data not collected.	NA Score on a Scale Standard Error NA Study terminated; data not collected.	NA Score on a Scale Standard Error NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline, Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants at selected sites who received at least one dose of study drug and had a Week 26, Week 52 or Week 104 assessment for sputum IL-8 level. The study was terminated during Period 2; no data were collected for this endpoint at Weeks 52 or 104.

Induced sputum samples were to be collected from participants via the nebulized method prior to study drug administration at Week 26, Week 52 and Week 104. IL-8 levels were measured by enzyme-linked immunosorbent assay (ELISA) in the sputum supernatant. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=38 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=36 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=48 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=42 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8) Baseline (n=38, 36, 48, 42)	29.736 pg/mL Standard Deviation 0.552	29.736 pg/mL Standard Deviation 0.552	29.736 pg/mL Standard Deviation 0.552	29.736 pg/mL Standard Deviation 0.552
Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8) Week 26 (n=24, 22, 19, 21)	35.392 pg/mL Standard Deviation 0.410	38.471 pg/mL Standard Deviation 0.410	31.693 pg/mL Standard Deviation 0.410	30.421 pg/mL Standard Deviation 0.410
Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8) Week 52 (n=0, 0, 0, 0)	NA pg/mL Standard Deviation NA Study terminated; data not collected.	NA pg/mL Standard Deviation NA Study terminated; data not collected.	NA pg/mL Standard Deviation NA Study terminated; data not collected.	NA pg/mL Standard Deviation NA Study terminated; data not collected.
Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8) Week 104 (n=0, 0, 0, 0)	NA pg/mL Standard Deviation NA Study terminated; data not collected.	NA pg/mL Standard Deviation NA Study terminated; data not collected.	NA pg/mL Standard Deviation NA Study terminated; data not collected.	NA pg/mL Standard Deviation NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline, Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants at selected sites who received at least one dose of study drug and had a Week 26, Week 52 or Week 104 assessment for sputum MPO level. The study was terminated during Period 2; no data were collected for this endpoint at Weeks 52 or 104.

Induced sputum samples were to be collected from participants via the nebulized method prior to study drug administration at Week 26, Week 52 and Week 104. MPO levels were measured by ELISA in the sputum supernatant. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=37 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=36 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=45 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=41 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO) Baseline (n=37, 36, 45, 41)	1.840 ng/mL Standard Deviation 1.120	1.840 ng/mL Standard Deviation 1.120	1.840 ng/mL Standard Deviation 1.120	1.840 ng/mL Standard Deviation 1.120
Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO) Week 26 (n=24, 22, 19, 20)	3.243 ng/mL Standard Deviation 1.488	1.747 ng/mL Standard Deviation 1.488	0.932 ng/mL Standard Deviation 1.488	3.656 ng/mL Standard Deviation 1.488
Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO) Week 52 (n=0, 0, 0, 0)	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.
Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO) Week 104 (n=0, 0, 0, 0)	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline, Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants at selected sites who received at least one dose of study drug and had a Week 26, Week 52 or Week 104 assessment for sputum neutrophil elastase level. The study was terminated during Period 2; no data were collected for this endpoint at Weeks 52 or 104.

Induced sputum samples were to be collected from participants via the nebulized method prior to study drug administration at Week 26, Week 52 and Week 104. Neutrophil elastase levels were measured in the sputum supernatant. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=36 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=34 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=43 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=37 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase Week 26 (n=23, 17, 19, 19)	16.785 ng/mL Standard Deviation 0.773	11.365 ng/mL Standard Deviation 0.773	19.106 ng/mL Standard Deviation 0.773	27.973 ng/mL Standard Deviation 0.773
Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase Baseline (n=36, 34, 43, 37)	16.948 ng/mL Standard Deviation 0.700	16.948 ng/mL Standard Deviation 0.700	16.948 ng/mL Standard Deviation 0.700	16.948 ng/mL Standard Deviation 0.700
Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase Week 52 (n=0, 0, 0, 0)	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.
Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase Week 104 (n=0, 0, 0, 0)	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline, Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants at selected sites who received at least one dose of study drug and had a Week 26, Week 52 or Week 104 assessment for induced sputum MMP-9 level. The study was terminated during Period 2; no data were collected for this endpoint at Weeks 52 or 104.

Induced sputum samples were to be collected from participants via the nebulized method prior to study drug administration at Week 26, Week 52 and Week 104. MMP-9 levels were measured by ELISA in the sputum supernatant. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=39 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=35 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=46 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=41 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9) Baseline (n=39, 35, 46, 41)	720.45 ng/mL Standard Deviation 0.773	720.45 ng/mL Standard Deviation 0.773	720.45 ng/mL Standard Deviation 0.773	720.45 ng/mL Standard Deviation 0.773
Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9) Week 26 (n=24, 22, 19, 21)	878.02 ng/mL Standard Deviation 0.709	711.90 ng/mL Standard Deviation 0.709	392.81 ng/mL Standard Deviation 0.709	1480.1 ng/mL Standard Deviation 0.709
Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9) Week 52 (n=0, 0, 0, 0)	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.
Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9) Week 104 (n=0, 0, 0, 0)	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline, Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants who received at least one dose of study drug and had a Week 26, Week 52 or Week 104 assessment for plasma hs-CRP level. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

Blood samples were to be collected prior to study drug administration to determine participant plasma hs-CRP levels at Week 26, Week 52 and Week 104. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=148 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=152 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=149 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=150 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP) Baseline (n=148, 152, 149, 150)	2.766 mg/dL Standard Deviation 0.498	2.766 mg/dL Standard Deviation 0.498	2.766 mg/dL Standard Deviation 0.498	2.766 mg/dL Standard Deviation 0.498
Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP) Week 26 (n=121, 104, 100, 126)	2.832 mg/dL Standard Deviation 0.443	3.728 mg/dL Standard Deviation 0.443	4.410 mg/dL Standard Deviation 0.443	2.889 mg/dL Standard Deviation 0.443
Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP) Week 52 (n=67, 49, 43, 68)	3.360 mg/dL Standard Deviation 0.432	3.871 mg/dL Standard Deviation 0.432	4.566 mg/dL Standard Deviation 0.432	2.657 mg/dL Standard Deviation 0.432
Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP) Week 104 (n=0, 0, 0, 0)	NA mg/dL Standard Deviation NA Study terminated; data not collected.	NA mg/dL Standard Deviation NA Study terminated; data not collected.	NA mg/dL Standard Deviation NA Study terminated; data not collected.	NA mg/dL Standard Deviation NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline, Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants who received at least one dose of study drug and had a Week 26, Week 52 or Week 104 assessment for plasma fibrinogen level. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

Blood samples were to be collected prior to study drug administration to determine participant plasma fibrinogen levels at Week 26, Week 52 and Week 104. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=140 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=138 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=138 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=143 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Plasma Inflammatory Biomarker Levels: Fibrinogen Baseline (n=140, 138, 138, 143)	3.731 mg/dL Standard Deviation 0.108	3.731 mg/dL Standard Deviation 0.108	3.731 mg/dL Standard Deviation 0.108	3.731 mg/dL Standard Deviation 0.108
Plasma Inflammatory Biomarker Levels: Fibrinogen Week 26 (n=111, 104, 91, 121)	3.835 mg/dL Standard Deviation 0.119	4.027 mg/dL Standard Deviation 0.119	4.068 mg/dL Standard Deviation 0.119	3.788 mg/dL Standard Deviation 0.119
Plasma Inflammatory Biomarker Levels: Fibrinogen Week 52 (n=52, 40, 38, 58)	4.163 mg/dL Standard Deviation 0.108	4.031 mg/dL Standard Deviation 0.108	4.308 mg/dL Standard Deviation 0.108	3.788 mg/dL Standard Deviation 0.108
Plasma Inflammatory Biomarker Levels: Fibrinogen Week 104 (n=0, 0, 0, 0)	NA mg/dL Standard Deviation NA Study terminated; data not collected.	NA mg/dL Standard Deviation NA Study terminated; data not collected.	NA mg/dL Standard Deviation NA Study terminated; data not collected.	NA mg/dL Standard Deviation NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline, Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants who received at least one dose of study drug and had a Week 26, Week 52 or Week 104 assessment for MPO level. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

Blood samples were to be collected prior to study drug administration to determine participant plasma MPO levels at Week 26, Week 52 and Week 104. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=146 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=145 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=147 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=148 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO) Week 26 (n=119, 104, 97, 124)	188.70 ng/mL Standard Deviation 0.439	175.80 ng/mL Standard Deviation 0.439	173.16 ng/mL Standard Deviation 0.439	227.72 ng/mL Standard Deviation 0.439
Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO) Week 52 (n=47, 36, 35, 46)	234.42 ng/mL Standard Deviation 0.451	196.67 ng/mL Standard Deviation 0.451	246.04 ng/mL Standard Deviation 0.451	254.20 ng/mL Standard Deviation 0.451
Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO) Week 104 (n=0, 0, 0, 0)	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.
Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO) Baseline (n=146, 145, 147, 148)	169.15 ng/mL Standard Deviation 0.386	169.15 ng/mL Standard Deviation 0.386	169.15 ng/mL Standard Deviation 0.386	169.15 ng/mL Standard Deviation 0.386

SECONDARY outcome

Timeframe: Baseline, Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants who received at least one dose of study drug and had a Week 26, Week 52 or Week 104 assessment for MMP-9 level. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

Blood samples were to be collected prior to study drug administration to determine participant plasma MMP-9 levels at Week 26, Week 52 and Week 104. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=146 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=145 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=147 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=148 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9) Baseline (n=146, 145, 147, 148)	294.80 ng/mL Standard Deviation 0.254	294.80 ng/mL Standard Deviation 0.254	294.80 ng/mL Standard Deviation 0.254	294.80 ng/mL Standard Deviation 0.254
Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9) Week 26 (n=119, 104, 97, 124)	247.63 ng/mL Standard Deviation 0.272	216.40 ng/mL Standard Deviation 0.272	217.79 ng/mL Standard Deviation 0.272	319.80 ng/mL Standard Deviation 0.272
Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9) Week 52 (n=48, 36, 35, 47)	258.82 ng/mL Standard Deviation 0.272	220.90 ng/mL Standard Deviation 0.272	244.67 ng/mL Standard Deviation 0.272	342.46 ng/mL Standard Deviation 0.272
Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9) Week 104 (n=0, 0, 0, 0)	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline, Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants who received at least one dose of study drug and had a Week 26, Week 52 or Week 104 assessment for plasma neutrophil elastase level. The study was terminated during Period 2; no data were collected for the endpoint at Week 104.

Blood samples were to be collected prior to study drug administration to determine participant plasma neutrophil elastase levels at Week 26, Week 52 and Week 104. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=123 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=117 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=122 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=121 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase Baseline (n=123, 117, 122, 121)	67.969 ng/mL Standard Deviation 0.323	67.969 ng/mL Standard Deviation 0.323	67.969 ng/mL Standard Deviation 0.323	67.969 ng/mL Standard Deviation 0.323
Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase Week 26 (n=118, 104, 93, 121)	63.592 ng/mL Standard Deviation 0.341	63.680 ng/mL Standard Deviation 0.341	65.413 ng/mL Standard Deviation 0.341	67.697 ng/mL Standard Deviation 0.341
Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase Week 52 (n=51, 41, 33, 52)	60.965 ng/mL Standard Deviation 0.280	54.267 ng/mL Standard Deviation 0.280	64.296 ng/mL Standard Deviation 0.280	57.804 ng/mL Standard Deviation 0.280
Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase Week 104 (n=0, 0, 0, 0)	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.	NA ng/mL Standard Deviation NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline, Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants who received at least one dose of study drug and had a Week 26, Week 52 or Week 104 assessment for ENA-78 level. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

Blood samples were to be collected prior to study drug administration to determine participant plasma ENA-78 levels at Week 26, Week 52 and Week 104. The reported Baseline LS means and SDs are pooled across all treatment groups. The rationale for the use of pooled Baseline LS mean and SD values is the assumption that the Baseline LS mean and SD values are similar across treatment groups. The reported post-Baseline SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=125 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=118 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=122 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=126 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78) Baseline (n=125, 118, 122, 126)	436.31 pg/mL Standard Deviation 0.430	436.31 pg/mL Standard Deviation 0.430	436.31 pg/mL Standard Deviation 0.430	436.31 pg/mL Standard Deviation 0.430
Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78) Week 26 (n=119, 105, 92, 121)	508.31 pg/mL Standard Deviation 0.451	543.60 pg/mL Standard Deviation 0.451	607.37 pg/mL Standard Deviation 0.451	473.10 pg/mL Standard Deviation 0.451
Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78) Week 52 (n=42, 32, 33, 42)	509.93 pg/mL Standard Deviation 0.409	603.44 pg/mL Standard Deviation 0.409	698.93 pg/mL Standard Deviation 0.409	417.90 pg/mL Standard Deviation 0.409
Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78) Week 104 (n=0, 0, 0, 0)	NA pg/mL Standard Deviation NA Study terminated; data not collected.	NA pg/mL Standard Deviation NA Study terminated; data not collected.	NA pg/mL Standard Deviation NA Study terminated; data not collected.	NA pg/mL Standard Deviation NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline and Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants at selected sites who received at least one dose of study drug and had a Baseline and Week 26, Week 52 or Week 104 assessment for pre- and post-6-minute-walk-test Borg scale score. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

The 6-minute walk test measured the distance participants could walk quickly on a flat, hard surface in 6 minutes. The Borg scale is a method use to rate perceived exertion (0=Nothing at all \[no exertion\] to 10=Maximal \[exertion\]). Borg scale scores were to be assessed pre- and post-walk-test at Baseline, Week 26, Week 52 and Week 104. A higher score indicates greater perceived exertion.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=84 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=77 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=68 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=87 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Change From Baseline in Pre- and Post-6-Minute-Walk-Test Borg Scale Score Pre-walk Change at Week 26 (n=84, 77, 68, 87)	-0.27 Score on a Scale Standard Error 0.12	0.07 Score on a Scale Standard Error 0.12	-0.13 Score on a Scale Standard Error 0.13	0.17 Score on a Scale Standard Error 0.12
Change From Baseline in Pre- and Post-6-Minute-Walk-Test Borg Scale Score Pre-walk Change at Week 52 (n=32, 25, 25, 30)	-0.18 Score on a Scale Standard Error 0.19	0.22 Score on a Scale Standard Error 0.21	0.08 Score on a Scale Standard Error 0.21	0.21 Score on a Scale Standard Error 0.20
Change From Baseline in Pre- and Post-6-Minute-Walk-Test Borg Scale Score Post-walk Change at Week 26 (n=84, 77, 68, 87)	-0.52 Score on a Scale Standard Error 0.14	-0.03 Score on a Scale Standard Error 0.15	0.10 Score on a Scale Standard Error 0.16	0.11 Score on a Scale Standard Error 0.14
Change From Baseline in Pre- and Post-6-Minute-Walk-Test Borg Scale Score Post-walk Change at Week 52 (n=32, 25, 25, 30)	-0.26 Score on a Scale Standard Error 0.26	0.52 Score on a Scale Standard Error 0.29	-0.16 Score on a Scale Standard Error 0.30	0.26 Score on a Scale Standard Error 0.27
Change From Baseline in Pre- and Post-6-Minute-Walk-Test Borg Scale Score Pre-walk Change at Week 104 (n=0, 0, 0, 0)	NA Score on a Scale Standard Error NA Study terminated; data not collected.	NA Score on a Scale Standard Error NA Study terminated; data not collected.	NA Score on a Scale Standard Error NA Study terminated; data not collected.	NA Score on a Scale Standard Error NA Study terminated; data not collected.
Change From Baseline in Pre- and Post-6-Minute-Walk-Test Borg Scale Score Post-walk Change at Week 104 (n=0, 0, 0, 0)	NA Score on a Scale Standard Error NA Study terminated; data not collected.	NA Score on a Scale Standard Error NA Study terminated; data not collected.	NA Score on a Scale Standard Error NA Study terminated; data not collected.	NA Score on a Scale Standard Error NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Baseline and Week 26, Week 52, Week 104

Population: The FAS population consisted of all participants at selected sites who received at least one dose of study drug and had a Baseline and Week 26, Week 52 or Week 104 assessment for pre- and post-6-minute-walk-test arterial oxygen saturation. The study was terminated during Period 2; no data were collected for this endpoint at Week 104.

The 6-minute walk test measured the distance participants could walk quickly on a flat, hard surface in 6 minutes. Percent (%) of arterial oxygen saturation, as measured by pulse oximetry, was to be assessed before and after the 6-minute walk test at Baseline, Week 26, Week 52 and Week 104.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=84 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=77 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=68 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=87 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Change From Baseline in Percent of Arterial Oxygen Saturation Measured by Pulse Oximetry Before and After the 6-Minute Walk Test Pre-walk Change at Week 26 (n=84, 77, 68, 87)	0.12 Percent Oxygen Saturation Standard Error 0.21	-0.70 Percent Oxygen Saturation Standard Error 0.22	-0.07 Percent Oxygen Saturation Standard Error 0.23	-0.02 Percent Oxygen Saturation Standard Error 0.21
Change From Baseline in Percent of Arterial Oxygen Saturation Measured by Pulse Oximetry Before and After the 6-Minute Walk Test Pre-walk Change at Week 52 (n=32, 25, 25, 30)	0.19 Percent Oxygen Saturation Standard Error 0.32	-0.08 Percent Oxygen Saturation Standard Error 0.36	-0.22 Percent Oxygen Saturation Standard Error 0.36	-0.00 Percent Oxygen Saturation Standard Error 0.33
Change From Baseline in Percent of Arterial Oxygen Saturation Measured by Pulse Oximetry Before and After the 6-Minute Walk Test Post-walk Change at Week 26 (n=84, 77, 68, 87)	0.26 Percent Oxygen Saturation Standard Error 0.32	-0.42 Percent Oxygen Saturation Standard Error 0.33	0.28 Percent Oxygen Saturation Standard Error 0.35	0.75 Percent Oxygen Saturation Standard Error 0.32
Change From Baseline in Percent of Arterial Oxygen Saturation Measured by Pulse Oximetry Before and After the 6-Minute Walk Test Post-walk Change at Week 52 (n=32, 25, 25, 30)	0.39 Percent Oxygen Saturation Standard Error 0.45	-0.33 Percent Oxygen Saturation Standard Error 0.49	0.63 Percent Oxygen Saturation Standard Error 0.50	0.19 Percent Oxygen Saturation Standard Error 0.46
Change From Baseline in Percent of Arterial Oxygen Saturation Measured by Pulse Oximetry Before and After the 6-Minute Walk Test Pre-walk Change at Week 104 (n=0, 0, 0, 0)	NA Percent Oxygen Saturation Standard Error NA Study terminated; data not collected.	NA Percent Oxygen Saturation Standard Error NA Study terminated; data not collected.	NA Percent Oxygen Saturation Standard Error NA Study terminated; data not collected.	NA Percent Oxygen Saturation Standard Error NA Study terminated; data not collected.
Change From Baseline in Percent of Arterial Oxygen Saturation Measured by Pulse Oximetry Before and After the 6-Minute Walk Test Post-walk Change at Week 104 (n=0, 0, 0, 0)	NA Percent Oxygen Saturation Standard Error NA Study terminated; data not collected.	NA Percent Oxygen Saturation Standard Error NA Study terminated; data not collected.	NA Percent Oxygen Saturation Standard Error NA Study terminated; data not collected.	NA Percent Oxygen Saturation Standard Error NA Study terminated; data not collected.

SECONDARY outcome

Timeframe: Up to 26 , 52 and 104 weeks

Population: The ASaT population consisted of all participants who received at least one dose of study drug. The study was terminated during Period 2; no data were analyzed for this endpoint for up to 104 weeks.

The percentage of participants who experienced an AE related to a respiratory infection or infestation, was to be calculated for the first 26 weeks, the first 52 weeks and the first 104 weeks of treatment.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=152 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=156 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=152 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=154 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Percentage of Participants Who Experienced an AE Related to Respiratory Infection Up to Week 26 (n=152, 165, 152, 154)	30.3 Percentage of Participants	30.1 Percentage of Participants	22.4 Percentage of Participants	24.0 Percentage of Participants
Percentage of Participants Who Experienced an AE Related to Respiratory Infection Up to Week 52 (n=75, 63, 55, 82)	41.3 Percentage of Participants	41.3 Percentage of Participants	38.2 Percentage of Participants	28.0 Percentage of Participants
Percentage of Participants Who Experienced an AE Related to Respiratory Infection Up to Week 104 (n=0, 0, 0, 0)	NA Percentage of Participants Study terminated; data not analyzed.	NA Percentage of Participants Study terminated; data not analyzed.	NA Percentage of Participants Study terminated; data not analyzed.	NA Percentage of Participants Study terminated; data not analyzed.

SECONDARY outcome

Timeframe: Up to 26 , 52 and 104 weeks

The percentage of participants who experienced an AE related to any type of infection or infestation, was to be calculated for the first 26 weeks, the first 52 weeks and the first 104 weeks of treatment.

Outcome measures

Outcome measures
Measure	Navarixin 10 mg n=152 Participants Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=156 Participants Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=152 Participants Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=154 Participants Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Percentage of Participants Who Experienced an AE Related to Any Type of Infection Up to Week 26 (n=152, 156, 152, 154)	34.2 Percentage of Participants	37.2 Percentage of Participants	27.0 Percentage of Participants	31.8 Percentage of Participants
Percentage of Participants Who Experienced an AE Related to Any Type of Infection Up to Week 52 (n=75, 63, 55, 82)	48.0 Percentage of Participants	46.0 Percentage of Participants	45.5 Percentage of Participants	35.4 Percentage of Participants
Percentage of Participants Who Experienced an AE Related to Any Type of Infection Up to Week 104 (n=0, 0, 0, 0)	NA Percentage of Participants Study terminated; data not analyzed.	NA Percentage of Participants Study terminated; data not analyzed.	NA Percentage of Participants Study terminated; data not analyzed.	NA Percentage of Participants Study terminated; data not analyzed.

Adverse Events

Navarixin 10 mg

Serious events: 26 serious events

Other events: 65 other events

Deaths: 0 deaths

Navarixin 30 mg

Serious events: 23 serious events

Other events: 75 other events

Deaths: 0 deaths

Navarixin 50 mg

Serious events: 20 serious events

Other events: 74 other events

Deaths: 0 deaths

Placebo

Serious events: 21 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Navarixin 10 mg n=152 participants at risk Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 30 mg n=156 participants at risk Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years	Navarixin 50 mg n=152 participants at risk Participants receive navarixin 50 mg, as two navarixin 10 mg capsules and one navarixin 30 mg capsule, administered orally QD for up to 2 years	Placebo n=154 participants at risk Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years
Infections and infestations Influenza	5.9% 9/152 • Number of events 11 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	1.9% 3/156 • Number of events 3 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	2.6% 4/152 • Number of events 4 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	2.6% 4/154 • Number of events 6 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	15.1% 23/152 • Number of events 38 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	17.9% 28/156 • Number of events 42 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	14.5% 22/152 • Number of events 34 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	14.3% 22/154 • Number of events 29 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.
Infections and infestations Rhinitis	5.3% 8/152 • Number of events 8 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	3.8% 6/156 • Number of events 7 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	2.0% 3/152 • Number of events 3 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	1.9% 3/154 • Number of events 3 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	1.3% 2/152 • Number of events 2 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	1.3% 2/156 • Number of events 2 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	2.0% 3/152 • Number of events 3 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	5.2% 8/154 • Number of events 11 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Overdose	2.6% 4/152 • Number of events 5 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	2.6% 4/156 • Number of events 4 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	5.3% 8/152 • Number of events 9 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	2.6% 4/154 • Number of events 4 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.
Investigations Neutrophil count decreased	3.9% 6/152 • Number of events 6 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	14.1% 22/156 • Number of events 22 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	21.1% 32/152 • Number of events 32 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	0.65% 1/154 • Number of events 1 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	6.6% 10/152 • Number of events 10 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	3.8% 6/156 • Number of events 7 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	5.3% 8/152 • Number of events 9 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	0.65% 1/154 • Number of events 1 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Headache	9.2% 14/152 • Number of events 27 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	12.8% 20/156 • Number of events 29 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	9.2% 14/152 • Number of events 21 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.	9.7% 15/154 • Number of events 22 • Up to one week after last dose of study drug (up to 105 weeks) The ASaT population consisted of all participants who received at least one dose of study drug.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

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 (including, without limitation, slides and texts of oral or other public presentations and texts of any transmission through any electronic media, e.g., any computer access system such as the Internet, World Wide Web, etc.) that report any results of the study.
Publication restrictions are in place

Restriction type: OTHER