Placebo to navarixin capsules

Short-acting β-agonist (SABA), anticholinergic, or a combination SABA/anticholinergic

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years

Total of all reporting groups

Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years

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

Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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. 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.

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. 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.

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. 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.

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.

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.

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 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.

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 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.

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 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.

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 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.

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 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.

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.

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.

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. 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.

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 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.

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 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.

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.

Participants receive navarixin 30 mg, as one navarixin 30 mg capsule and two placebo capsules, administered orally QD for up to 2 years

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

Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years