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

A 2-Year, Dose Range-Finding, Adaptive-Design Study of the Effects of SCH 527123 in Subjects With Moderate to Severe COPD

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01006616

Enrollment

616

Registered

2009-11-03

Start date

2009-10-01

Completion date

2011-11-01

Last updated

2019-01-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

COPD

Brief summary

Neutrophils are thought to play an important role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Navarixin (SCH 527123, MK-7123) is an antagonist of the cysteine-X-cysteine chemokine receptor 2 (CXCR2) and is thought to reduce neutrophil migration to the diseased lung. It is theorized that reducing neutrophil migration to the diseased lung will improve a participant's symptoms and the natural history of the disease. The study will consist of a 2-week screening period followed by a 2-year (104-week) double-blind treatment period. The 2-year Treatment Period will be made up of two phases: a 26-week (6-month) dose range-finding phase with 3 active arms and 1 placebo arm (Period 1), followed by a 78-week (18-month) long-term safety and efficacy phase (Period 2). Participants participating in the original 6-month study (Period 1) may elect not to continue into the 18-month extension study (Period 2). Hypothesis: navarixin, 50 mg, or the highest remaining dose if the 50-mg dose is discontinued, is superior to placebo with respect to improving airflow.

Interventions

DRUGNavarixin

Navarixin 10 mg and 30 mg capsules

DRUGPlacebo

Placebo to navarixin capsules

DRUGRescue medication

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

41 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Diagnosis of COPD for at least 2 years based on American Thoracic Society/European Respiratory Society (ATS/ERS) current guidelines or symptoms consistent with COPD for at least 2 years. * \>40 to \<=75 years of age, of either sex, and of any race. * No exacerbation or respiratory infection in the past 6 weeks. * Smoker or ex-smoker with more than 10 pack-year history.

Exclusion criteria

* Diagnosis of asthma or other clinically relevant lung disease (other than COPD), i.e., sarcoidosis, tuberculosis, pulmonary fibrosis, severe bronchiectasis, or lung cancer. * Significant X-ray findings. * Use of supplemental oxygen for \>12 hours/day.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (Period 1)	Baseline and Week 26	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.
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 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.

Secondary

Measure	Time frame	Description
Change From Baseline in Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity (FEF25%-75%) Test	Baseline and Week 26, Week 52, 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.
Percentage of Participants With a Moderate to Severe COPD Exacerbation	Up to 26, 52 and 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.
Total Exacerbations of Chronic Pulmonary Disease Tool-Patient-Recorded Outcome (EXACT-PRO) Questionnaire Score	At 26, 52 and 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.
Induced Sputum Absolute Neutrophil Counts	Baseline, Week 26, Week 52, 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.
Change From Baseline in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score	Baseline and Week 26, Week 52, 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.
Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test)	Baseline and Week 26, Week 52, 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.
Change From Baseline in Pre-bronchodilator FEV1	Baseline and Week 26, Week 52, 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.
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)	Baseline and Week 26, Week 52, 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.
Change From Baseline in Functional Residual Capacity (FRC)	Baseline and Week 26, Week 52, 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.
Change From Baseline in Total Lung Capacity (TLC)	Baseline and Week 26, Week 52, 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.
Change From Baseline in Inspiratory Capacity (IC)	Baseline and Week 26, Week 52, 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.
Change From Baseline in Morning Peak Expiratory Flow (PEF)	Baseline and Week 26, Week 52, 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.
Change From Baseline in Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Index Score	Baseline and Week 26, Week 52, 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.
Change From Baseline in Modified Medical Research Council (MMRC) Dyspnea Score	Baseline and Week 26, Week 52, 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.
Change From Baseline in Post-bronchodilator FEV1 (Period 2)	Baseline and Week 52, 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.
Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)	Baseline, Week 26, Week 52, 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. 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.
Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase	Baseline, Week 26, Week 52, 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. 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.
Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)	Baseline, Week 26, Week 52, 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. 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.
Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP)	Baseline, Week 26, Week 52, 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.
Plasma Inflammatory Biomarker Levels: Fibrinogen	Baseline, Week 26, Week 52, 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.
Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)	Baseline, Week 26, Week 52, 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.
Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)	Baseline, Week 26, Week 52, 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.
Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase	Baseline, Week 26, Week 52, 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.
Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78)	Baseline, Week 26, Week 52, 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.
Change From Baseline in Pre- and Post-6-Minute-Walk-Test Borg Scale Score	Baseline and Week 26, Week 52, 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.
Change From Baseline in Percent of Arterial Oxygen Saturation Measured by Pulse Oximetry Before and After the 6-Minute Walk Test	Baseline and Week 26, Week 52, 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.
Percentage of Participants Who Experienced an AE Related to Respiratory Infection	Up to 26 , 52 and 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.
Percentage of Participants Who Experienced an AE Related to Any Type of Infection	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.
Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)	Baseline, Week 26, Week 52, 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.
Number of Participants With a Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	Up to 26 , 52 and 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.

Participant flow

Participants by arm

Arm	Count
Navarixin 10 mg Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally QD for up to 2 years	152
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	156
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	152
Placebo Participants receive placebo to navarixin, as three placebo capsules, administered orally QD for up to 2 years	154
Total	614

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Period 1 (6 Months)	Adverse Event	10	31	37	9
Period 1 (6 Months)	Did Not Meet Protocol Eligibility	5	7	5	5
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)	Noncompliance With Protocol	0	2	2	3
Period 1 (6 Months)	Not Treated	0	0	1	1
Period 1 (6 Months)	Withdrawal by Subject	2	2	2	0
Period 1 (6 Months)	Withdrew, Reason Related to Treatment	0	3	1	2
Period 1 (6 Months)	Withdrew, Reason Unrelated to Treatment	6	5	2	3
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)	Noncompliance With Protocol	0	1	0	1
Period 2 (18 Months)	Study Terminated	63	46	44	70
Period 2 (18 Months)	Withdrawal by Subject	1	4	0	1
Period 2 (18 Months)	Withdrew, Reason Related to Treatment	0	6	1	2
Period 2 (18 Months)	Withdrew, Reason Unrelated to Treatment	3	0	3	2

Baseline characteristics

Characteristic	Navarixin 10 mg	Navarixin 30 mg	Navarixin 50 mg	Placebo	Total
Age, Continuous	63.7 Years STANDARD_DEVIATION 6.9	63.2 Years STANDARD_DEVIATION 7.4	61.3 Years STANDARD_DEVIATION 7.5	63.3 Years STANDARD_DEVIATION 7.2	62.9 Years STANDARD_DEVIATION 7.3
Sex: Female, Male Female	28 Participants	52 Participants	50 Participants	46 Participants	176 Participants
Sex: Female, Male Male	124 Participants	104 Participants	102 Participants	108 Participants	438 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	65 / 152	75 / 156	74 / 152	46 / 154
serious Total, serious adverse events	26 / 152	23 / 156	20 / 152	21 / 154

Outcome results

Primary

Change From Baseline in Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (Period 1)

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.

Time frame: 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.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	Change From Baseline in Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (Period 1)	-0.009 Liters	Standard Error 0.022
Navarixin 30 mg	Change From Baseline in Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (Period 1)	-0.068 Liters	Standard Error 0.023
Navarixin 50 mg	Change From Baseline in Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (Period 1)	0.028 Liters	Standard Error 0.024
Placebo	Change From Baseline in Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (Period 1)	-0.039 Liters	Standard Error 0.022

p-value: 0.32595% CI: [-0.03, 0.091]Constrained Longitudinal Data Analysis

p-value: 0.3795% CI: [-0.091, 0.034]Constrained Longitudinal Data Analysis

p-value: 0.03795% CI: [0.004, 0.131]Constrained Longitudinal Data Analysis

Primary

Percentage of Participants With an Adverse Event (AE) Related to a Blood Absolute Neutrophil Count (ANC) of Less Than 1.5x10^9 Cells/L

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.

Time frame: 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.

Arm	Measure	Group	Value (NUMBER)
Navarixin 10 mg	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
Navarixin 10 mg	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
Navarixin 10 mg	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
Navarixin 30 mg	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
Navarixin 30 mg	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)	12.8 Percentage of Participants
Navarixin 30 mg	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
Navarixin 50 mg	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)	20.4 Percentage of Participants
Navarixin 50 mg	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
Navarixin 50 mg	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
Placebo	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
Placebo	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
Placebo	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)	0.6 Percentage of Participants

p-value: 0.09695% CI: [-0.6, 6.9]Miettinen and Nurminen

p-value: <0.00195% CI: [7.4, 18.4]Miettinen and Nurminen

p-value: <0.00195% CI: [13.8, 26.9]Miettinen and Nurminen

Secondary

Change From Baseline in Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Index Score

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	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
Navarixin 10 mg	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	—
Navarixin 10 mg	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
Navarixin 30 mg	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)	0.13 Score on a Scale	Standard Error 0.13
Navarixin 30 mg	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	—
Navarixin 30 mg	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)	-0.02 Score on a Scale	Standard Error 0.25
Navarixin 50 mg	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)	0.09 Score on a Scale	Standard Error 0.24
Navarixin 50 mg	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)	-0.21 Score on a Scale	Standard Error 0.13
Navarixin 50 mg	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	—
Placebo	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)	0.07 Score on a Scale	Standard Error 0.12
Placebo	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	—
Placebo	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)	0.12 Score on a Scale	Standard Error 0.22

Secondary

Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test)

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	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
Navarixin 10 mg	Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test)	Change at Week 104 (n=0, 0, 0, 0)	NA Meters	—
Navarixin 10 mg	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 11.5
Navarixin 30 mg	Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test)	Change at Week 26 (n=84, 77, 68, 87)	-1.04 Meters	Standard Error 6.79
Navarixin 30 mg	Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test)	Change at Week 104 (n=0, 0, 0, 0)	NA Meters	—
Navarixin 30 mg	Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test)	Change at Week 52 (n=32, 25, 25, 30)	-33.58 Meters	Standard Error 12.74
Navarixin 50 mg	Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test)	Change at Week 52 (n=32, 25, 25, 30)	0.93 Meters	Standard Error 12.84
Navarixin 50 mg	Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test)	Change at Week 26 (n=84, 77, 68, 87)	2.06 Meters	Standard Error 7.19
Navarixin 50 mg	Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test)	Change at Week 104 (n=0, 0, 0, 0)	NA Meters	—
Placebo	Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test)	Change at Week 26 (n=84, 77, 68, 87)	7.41 Meters	Standard Error 6.45
Placebo	Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test)	Change at Week 104 (n=0, 0, 0, 0)	NA Meters	—
Placebo	Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test)	Change at Week 52 (n=32, 25, 25, 30)	-15.37 Meters	Standard Error 11.77

Secondary

Change From Baseline in Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity (FEF25%-75%) Test

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	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
Navarixin 10 mg	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	—
Navarixin 10 mg	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 0.02
Navarixin 30 mg	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)	-0.053 Liters/minute	Standard Error 0.017
Navarixin 30 mg	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	—
Navarixin 30 mg	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)	-0.055 Liters/minute	Standard Error 0.022
Navarixin 50 mg	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)	0.031 Liters/minute	Standard Error 0.023
Navarixin 50 mg	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)	0.028 Liters/minute	Standard Error 0.017
Navarixin 50 mg	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	—
Placebo	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)	-0.022 Liters/minute	Standard Error 0.016
Placebo	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	—
Placebo	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)	-0.018 Liters/minute	Standard Error 0.02

Secondary

Change From Baseline in Functional Residual Capacity (FRC)

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	Change From Baseline in Functional Residual Capacity (FRC)	Change at Week 26 (n=65, 55, 50, 59)	0.15 Liters	Standard Error 0.11
Navarixin 10 mg	Change From Baseline in Functional Residual Capacity (FRC)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Navarixin 10 mg	Change From Baseline in Functional Residual Capacity (FRC)	Change at Week 52 (n=24, 21, 18, 21)	0.21 Liters	Standard Error 0.13
Navarixin 30 mg	Change From Baseline in Functional Residual Capacity (FRC)	Change at Week 26 (n=65, 55, 50, 59)	-0.11 Liters	Standard Error 0.12
Navarixin 30 mg	Change From Baseline in Functional Residual Capacity (FRC)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Navarixin 30 mg	Change From Baseline in Functional Residual Capacity (FRC)	Change at Week 52 (n=24, 21, 18, 21)	0.12 Liters	Standard Error 0.14
Navarixin 50 mg	Change From Baseline in Functional Residual Capacity (FRC)	Change at Week 52 (n=24, 21, 18, 21)	0.10 Liters	Standard Error 0.15
Navarixin 50 mg	Change From Baseline in Functional Residual Capacity (FRC)	Change at Week 26 (n=65, 55, 50, 59)	-0.07 Liters	Standard Error 0.12
Navarixin 50 mg	Change From Baseline in Functional Residual Capacity (FRC)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Placebo	Change From Baseline in Functional Residual Capacity (FRC)	Change at Week 26 (n=65, 55, 50, 59)	0.07 Liters	Standard Error 0.11
Placebo	Change From Baseline in Functional Residual Capacity (FRC)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Placebo	Change From Baseline in Functional Residual Capacity (FRC)	Change at Week 52 (n=24, 21, 18, 21)	0.13 Liters	Standard Error 0.14

Secondary

Change From Baseline in Inspiratory Capacity (IC)

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	Change From Baseline in Inspiratory Capacity (IC)	Change at Week 26 (n=66, 55, 50, 60)	-0.04 Liters	Standard Error 0.05
Navarixin 10 mg	Change From Baseline in Inspiratory Capacity (IC)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Navarixin 10 mg	Change From Baseline in Inspiratory Capacity (IC)	Change at Week 52 (n=24, 21, 18, 21)	-0.02 Liters	Standard Error 0.08
Navarixin 30 mg	Change From Baseline in Inspiratory Capacity (IC)	Change at Week 26 (n=66, 55, 50, 60)	-0.05 Liters	Standard Error 0.06
Navarixin 30 mg	Change From Baseline in Inspiratory Capacity (IC)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Navarixin 30 mg	Change From Baseline in Inspiratory Capacity (IC)	Change at Week 52 (n=24, 21, 18, 21)	-0.12 Liters	Standard Error 0.09
Navarixin 50 mg	Change From Baseline in Inspiratory Capacity (IC)	Change at Week 52 (n=24, 21, 18, 21)	0.04 Liters	Standard Error 0.09
Navarixin 50 mg	Change From Baseline in Inspiratory Capacity (IC)	Change at Week 26 (n=66, 55, 50, 60)	0.01 Liters	Standard Error 0.06
Navarixin 50 mg	Change From Baseline in Inspiratory Capacity (IC)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Placebo	Change From Baseline in Inspiratory Capacity (IC)	Change at Week 26 (n=66, 55, 50, 60)	-0.05 Liters	Standard Error 0.06
Placebo	Change From Baseline in Inspiratory Capacity (IC)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Placebo	Change From Baseline in Inspiratory Capacity (IC)	Change at Week 52 (n=24, 21, 18, 21)	0.02 Liters	Standard Error 0.09

Secondary

Change From Baseline in Modified Medical Research Council (MMRC) Dyspnea Score

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	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
Navarixin 10 mg	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	—
Navarixin 10 mg	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
Navarixin 30 mg	Change From Baseline in Modified Medical Research Council (MMRC) Dyspnea Score	Change at Week 26 (n=83, 75, 68, 86)	-0.02 Score on a Scale	Standard Error 0.09
Navarixin 30 mg	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	—
Navarixin 30 mg	Change From Baseline in Modified Medical Research Council (MMRC) Dyspnea Score	Change at Week 52 (n=33, 28, 25, 31)	0.05 Score on a Scale	Standard Error 0.16
Navarixin 50 mg	Change From Baseline in Modified Medical Research Council (MMRC) Dyspnea Score	Change at Week 52 (n=33, 28, 25, 31)	-0.09 Score on a Scale	Standard Error 0.17
Navarixin 50 mg	Change From Baseline in Modified Medical Research Council (MMRC) Dyspnea Score	Change at Week 26 (n=83, 75, 68, 86)	-0.24 Score on a Scale	Standard Error 0.09
Navarixin 50 mg	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	—
Placebo	Change From Baseline in Modified Medical Research Council (MMRC) Dyspnea Score	Change at Week 26 (n=83, 75, 68, 86)	-0.07 Score on a Scale	Standard Error 0.08
Placebo	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	—
Placebo	Change From Baseline in Modified Medical Research Council (MMRC) Dyspnea Score	Change at Week 52 (n=33, 28, 25, 31)	-0.07 Score on a Scale	Standard Error 0.15

Secondary

Change From Baseline in Morning Peak Expiratory Flow (PEF)

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	Change From Baseline in Morning Peak Expiratory Flow (PEF)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters/minute	—
Navarixin 10 mg	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
Navarixin 10 mg	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
Navarixin 30 mg	Change From Baseline in Morning Peak Expiratory Flow (PEF)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters/minute	—
Navarixin 30 mg	Change From Baseline in Morning Peak Expiratory Flow (PEF)	Change at Week 26 (n=119, 97, 95, 122)	-20.5 Liters/minute	Standard Error 4.5
Navarixin 30 mg	Change From Baseline in Morning Peak Expiratory Flow (PEF)	Change at Week 52 (n=61, 48, 43, 63)	-22.9 Liters/minute	Standard Error 10.88
Navarixin 50 mg	Change From Baseline in Morning Peak Expiratory Flow (PEF)	Change at Week 26 (n=119, 97, 95, 122)	-11.6 Liters/minute	Standard Error 4.61
Navarixin 50 mg	Change From Baseline in Morning Peak Expiratory Flow (PEF)	Change at Week 52 (n=61, 48, 43, 63)	-0.48 Liters/minute	Standard Error 11.5
Navarixin 50 mg	Change From Baseline in Morning Peak Expiratory Flow (PEF)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters/minute	—
Placebo	Change From Baseline in Morning Peak Expiratory Flow (PEF)	Change at Week 26 (n=119, 97, 95, 122)	-21.8 Liters/minute	Standard Error 4.26
Placebo	Change From Baseline in Morning Peak Expiratory Flow (PEF)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters/minute	—
Placebo	Change From Baseline in Morning Peak Expiratory Flow (PEF)	Change at Week 52 (n=61, 48, 43, 63)	-26.2 Liters/minute	Standard Error 9.54

Secondary

Change From Baseline in Percent of Arterial Oxygen Saturation Measured by Pulse Oximetry Before and After the 6-Minute Walk Test

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	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
Navarixin 10 mg	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
Navarixin 10 mg	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
Navarixin 10 mg	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
Navarixin 10 mg	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	—
Navarixin 10 mg	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	—
Navarixin 30 mg	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	—
Navarixin 30 mg	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)	-0.33 Percent Oxygen Saturation	Standard Error 0.49
Navarixin 30 mg	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)	-0.70 Percent Oxygen Saturation	Standard Error 0.22
Navarixin 30 mg	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)	-0.42 Percent Oxygen Saturation	Standard Error 0.33
Navarixin 30 mg	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)	-0.08 Percent Oxygen Saturation	Standard Error 0.36
Navarixin 30 mg	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	—
Navarixin 50 mg	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)	-0.22 Percent Oxygen Saturation	Standard Error 0.36
Navarixin 50 mg	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)	0.28 Percent Oxygen Saturation	Standard Error 0.35
Navarixin 50 mg	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)	0.63 Percent Oxygen Saturation	Standard Error 0.5
Navarixin 50 mg	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	—
Navarixin 50 mg	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	—
Navarixin 50 mg	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)	-0.07 Percent Oxygen Saturation	Standard Error 0.23
Placebo	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	—
Placebo	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	—
Placebo	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)	-0.00 Percent Oxygen Saturation	Standard Error 0.33
Placebo	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)	0.19 Percent Oxygen Saturation	Standard Error 0.46
Placebo	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)	-0.02 Percent Oxygen Saturation	Standard Error 0.21
Placebo	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)	0.75 Percent Oxygen Saturation	Standard Error 0.32

Secondary

Change From Baseline in Post-bronchodilator FEV1 (Period 2)

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	Change From Baseline in Post-bronchodilator FEV1 (Period 2)	Week 52 (n=66, 47, 44, 65)	-0.047 Liters	Standard Error 0.027
Navarixin 10 mg	Change From Baseline in Post-bronchodilator FEV1 (Period 2)	Week 104 (n=0, 0, 0, 0)	NA Liters	—
Navarixin 30 mg	Change From Baseline in Post-bronchodilator FEV1 (Period 2)	Week 104 (n=0, 0, 0, 0)	NA Liters	—
Navarixin 30 mg	Change From Baseline in Post-bronchodilator FEV1 (Period 2)	Week 52 (n=66, 47, 44, 65)	-0.084 Liters	Standard Error 0.031
Navarixin 50 mg	Change From Baseline in Post-bronchodilator FEV1 (Period 2)	Week 52 (n=66, 47, 44, 65)	0.028 Liters	Standard Error 0.032
Navarixin 50 mg	Change From Baseline in Post-bronchodilator FEV1 (Period 2)	Week 104 (n=0, 0, 0, 0)	NA Liters	—
Placebo	Change From Baseline in Post-bronchodilator FEV1 (Period 2)	Week 52 (n=66, 47, 44, 65)	-0.031 Liters	Standard Error 0.027
Placebo	Change From Baseline in Post-bronchodilator FEV1 (Period 2)	Week 104 (n=0, 0, 0, 0)	NA Liters	—

Secondary

Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)	Change at Week 26 (n=124, 105, 102, 127)	-0.020 Liters	Standard Error 0.04
Navarixin 10 mg	Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Navarixin 10 mg	Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)	Change at Week 52 (n=66, 47, 44, 65)	-0.106 Liters	Standard Error 0.05
Navarixin 30 mg	Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)	Change at Week 26 (n=124, 105, 102, 127)	-0.089 Liters	Standard Error 0.042
Navarixin 30 mg	Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Navarixin 30 mg	Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)	Change at Week 52 (n=66, 47, 44, 65)	-0.077 Liters	Standard Error 0.057
Navarixin 50 mg	Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)	Change at Week 52 (n=66, 47, 44, 65)	0.039 Liters	Standard Error 0.059
Navarixin 50 mg	Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)	Change at Week 26 (n=124, 105, 102, 127)	-0.009 Liters	Standard Error 0.043
Navarixin 50 mg	Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Placebo	Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)	Change at Week 26 (n=124, 105, 102, 127)	-0.086 Liters	Standard Error 0.039
Placebo	Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Placebo	Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)	Change at Week 52 (n=66, 47, 44, 65)	-0.057 Liters	Standard Error 0.05

Secondary

Change From Baseline in Pre- and Post-6-Minute-Walk-Test Borg Scale Score

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	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	—
Navarixin 10 mg	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	—
Navarixin 10 mg	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
Navarixin 10 mg	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
Navarixin 10 mg	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
Navarixin 10 mg	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
Navarixin 30 mg	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)	0.52 Score on a Scale	Standard Error 0.29
Navarixin 30 mg	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)	0.22 Score on a Scale	Standard Error 0.21
Navarixin 30 mg	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	—
Navarixin 30 mg	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)	0.07 Score on a Scale	Standard Error 0.12
Navarixin 30 mg	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	—
Navarixin 30 mg	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)	-0.03 Score on a Scale	Standard Error 0.15
Navarixin 50 mg	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	—
Navarixin 50 mg	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)	-0.13 Score on a Scale	Standard Error 0.13
Navarixin 50 mg	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)	0.08 Score on a Scale	Standard Error 0.21
Navarixin 50 mg	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)	-0.16 Score on a Scale	Standard Error 0.3
Navarixin 50 mg	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)	0.10 Score on a Scale	Standard Error 0.16
Navarixin 50 mg	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	—
Placebo	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)	0.11 Score on a Scale	Standard Error 0.14
Placebo	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 0.27
Placebo	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	—
Placebo	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)	0.21 Score on a Scale	Standard Error 0.2
Placebo	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	—
Placebo	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)	0.17 Score on a Scale	Standard Error 0.12

Secondary

Change From Baseline in Pre-bronchodilator FEV1

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	Change From Baseline in Pre-bronchodilator FEV1	Change at Week 26 (n=124, 104, 103 126)	-0.035 Liters	Standard Error 0.021
Navarixin 10 mg	Change From Baseline in Pre-bronchodilator FEV1	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Navarixin 10 mg	Change From Baseline in Pre-bronchodilator FEV1	Change at Week 52 (n=65, 47, 43, 67)	-0.049 Liters	Standard Error 0.025
Navarixin 30 mg	Change From Baseline in Pre-bronchodilator FEV1	Change at Week 26 (n=124, 104, 103 126)	-0.084 Liters	Standard Error 0.022
Navarixin 30 mg	Change From Baseline in Pre-bronchodilator FEV1	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Navarixin 30 mg	Change From Baseline in Pre-bronchodilator FEV1	Change at Week 52 (n=65, 47, 43, 67)	-0.084 Liters	Standard Error 0.028
Navarixin 50 mg	Change From Baseline in Pre-bronchodilator FEV1	Change at Week 52 (n=65, 47, 43, 67)	0.019 Liters	Standard Error 0.029
Navarixin 50 mg	Change From Baseline in Pre-bronchodilator FEV1	Change at Week 26 (n=124, 104, 103 126)	0.008 Liters	Standard Error 0.022
Navarixin 50 mg	Change From Baseline in Pre-bronchodilator FEV1	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Placebo	Change From Baseline in Pre-bronchodilator FEV1	Change at Week 26 (n=124, 104, 103 126)	-0.054 Liters	Standard Error 0.021
Placebo	Change From Baseline in Pre-bronchodilator FEV1	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Placebo	Change From Baseline in Pre-bronchodilator FEV1	Change at Week 52 (n=65, 47, 43, 67)	-0.073 Liters	Standard Error 0.025

Secondary

Change From Baseline in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	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
Navarixin 10 mg	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	—
Navarixin 10 mg	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
Navarixin 30 mg	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)	-2.28 Score on a Scale	Standard Error 1.21
Navarixin 30 mg	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	—
Navarixin 30 mg	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)	-2.22 Score on a Scale	Standard Error 1.73
Navarixin 50 mg	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)	-3.86 Score on a Scale	Standard Error 1.8
Navarixin 50 mg	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)	-4.63 Score on a Scale	Standard Error 1.23
Navarixin 50 mg	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	—
Placebo	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)	-1.60 Score on a Scale	Standard Error 1.15
Placebo	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	—
Placebo	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)	-4.40 Score on a Scale	Standard Error 1.57

Secondary

Change From Baseline in Total Lung Capacity (TLC)

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	Change From Baseline in Total Lung Capacity (TLC)	Change at Week 26 (n=65, 55, 50, 59)	0.11 Liters	Standard Error 0.11
Navarixin 10 mg	Change From Baseline in Total Lung Capacity (TLC)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Navarixin 10 mg	Change From Baseline in Total Lung Capacity (TLC)	Change at Week 52 (n=24, 21, 18, 21)	0.15 Liters	Standard Error 0.13
Navarixin 30 mg	Change From Baseline in Total Lung Capacity (TLC)	Change at Week 26 (n=65, 55, 50, 59)	-0.14 Liters	Standard Error 0.12
Navarixin 30 mg	Change From Baseline in Total Lung Capacity (TLC)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Navarixin 30 mg	Change From Baseline in Total Lung Capacity (TLC)	Change at Week 52 (n=24, 21, 18, 21)	0.01 Liters	Standard Error 0.14
Navarixin 50 mg	Change From Baseline in Total Lung Capacity (TLC)	Change at Week 52 (n=24, 21, 18, 21)	0.13 Liters	Standard Error 0.15
Navarixin 50 mg	Change From Baseline in Total Lung Capacity (TLC)	Change at Week 26 (n=65, 55, 50, 59)	-0.06 Liters	Standard Error 0.12
Navarixin 50 mg	Change From Baseline in Total Lung Capacity (TLC)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Placebo	Change From Baseline in Total Lung Capacity (TLC)	Change at Week 26 (n=65, 55, 50, 59)	0.03 Liters	Standard Error 0.11
Placebo	Change From Baseline in Total Lung Capacity (TLC)	Change at Week 104 (n=0, 0, 0, 0)	NA Liters	—
Placebo	Change From Baseline in Total Lung Capacity (TLC)	Change at Week 52 (n=24, 21, 18, 21)	0.11 Liters	Standard Error 0.14

Secondary

Induced Sputum Absolute Neutrophil Counts

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	Induced Sputum Absolute Neutrophil Counts	Baseline (n=30, 29, 33, 33)	1.485 10^9 cells/L	Standard Deviation 0.706
Navarixin 10 mg	Induced Sputum Absolute Neutrophil Counts	Week 26 (n=23, 13, 13, 17)	1.763 10^9 cells/L	Standard Deviation 0.736
Navarixin 10 mg	Induced Sputum Absolute Neutrophil Counts	Week 52 (n=9, 8, 3, 3)	2.884 10^9 cells/L	Standard Deviation 0.462
Navarixin 10 mg	Induced Sputum Absolute Neutrophil Counts	Week 104 (n=0, 0, 0, 0)	NA 10^9 cells/L	—
Navarixin 30 mg	Induced Sputum Absolute Neutrophil Counts	Week 26 (n=23, 13, 13, 17)	2.073 10^9 cells/L	Standard Deviation 0.736
Navarixin 30 mg	Induced Sputum Absolute Neutrophil Counts	Week 104 (n=0, 0, 0, 0)	NA 10^9 cells/L	—
Navarixin 30 mg	Induced Sputum Absolute Neutrophil Counts	Baseline (n=30, 29, 33, 33)	1.485 10^9 cells/L	Standard Deviation 0.706
Navarixin 30 mg	Induced Sputum Absolute Neutrophil Counts	Week 52 (n=9, 8, 3, 3)	2.022 10^9 cells/L	Standard Deviation 0.462
Navarixin 50 mg	Induced Sputum Absolute Neutrophil Counts	Week 52 (n=9, 8, 3, 3)	1.253 10^9 cells/L	Standard Deviation 0.462
Navarixin 50 mg	Induced Sputum Absolute Neutrophil Counts	Week 104 (n=0, 0, 0, 0)	NA 10^9 cells/L	—
Navarixin 50 mg	Induced Sputum Absolute Neutrophil Counts	Baseline (n=30, 29, 33, 33)	1.485 10^9 cells/L	Standard Deviation 0.706
Navarixin 50 mg	Induced Sputum Absolute Neutrophil Counts	Week 26 (n=23, 13, 13, 17)	0.860 10^9 cells/L	Standard Deviation 0.736
Placebo	Induced Sputum Absolute Neutrophil Counts	Week 104 (n=0, 0, 0, 0)	NA 10^9 cells/L	—
Placebo	Induced Sputum Absolute Neutrophil Counts	Baseline (n=30, 29, 33, 33)	1.485 10^9 cells/L	Standard Deviation 0.706
Placebo	Induced Sputum Absolute Neutrophil Counts	Week 26 (n=23, 13, 13, 17)	2.121 10^9 cells/L	Standard Deviation 0.736
Placebo	Induced Sputum Absolute Neutrophil Counts	Week 52 (n=9, 8, 3, 3)	3.218 10^9 cells/L	Standard Deviation 0.462

Secondary

Number of Participants With a Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

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.

Time frame: 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.

Arm	Measure	Group	Value (NUMBER)
Navarixin 10 mg	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
Navarixin 10 mg	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
Navarixin 10 mg	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
Navarixin 30 mg	Number of Participants With a Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	Up to Week 26 (n=152, 156, 152, 154)	50 Participants
Navarixin 30 mg	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
Navarixin 30 mg	Number of Participants With a Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	Up to Week 52 (n=152, 156, 152, 154)	58 Participants
Navarixin 50 mg	Number of Participants With a Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	Up to Week 52 (n=152, 156, 152, 154)	51 Participants
Navarixin 50 mg	Number of Participants With a Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	Up to Week 26 (n=152, 156, 152, 154)	45 Participants
Navarixin 50 mg	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
Placebo	Number of Participants With a Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	Up to Week 26 (n=152, 156, 152, 154)	48 Participants
Placebo	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
Placebo	Number of Participants With a Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	Up to Week 52 (n=152, 156, 152, 154)	53 Participants

Secondary

Percentage of Participants Who Experienced an AE Related to Any Type of Infection

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.

Time frame: 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.

Arm	Measure	Group	Value (NUMBER)
Navarixin 10 mg	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
Navarixin 10 mg	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
Navarixin 10 mg	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
Navarixin 30 mg	Percentage of Participants Who Experienced an AE Related to Any Type of Infection	Up to Week 26 (n=152, 156, 152, 154)	37.2 Percentage of Participants
Navarixin 30 mg	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
Navarixin 30 mg	Percentage of Participants Who Experienced an AE Related to Any Type of Infection	Up to Week 52 (n=75, 63, 55, 82)	46.0 Percentage of Participants
Navarixin 50 mg	Percentage of Participants Who Experienced an AE Related to Any Type of Infection	Up to Week 52 (n=75, 63, 55, 82)	45.5 Percentage of Participants
Navarixin 50 mg	Percentage of Participants Who Experienced an AE Related to Any Type of Infection	Up to Week 26 (n=152, 156, 152, 154)	27.0 Percentage of Participants
Navarixin 50 mg	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
Placebo	Percentage of Participants Who Experienced an AE Related to Any Type of Infection	Up to Week 26 (n=152, 156, 152, 154)	31.8 Percentage of Participants
Placebo	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
Placebo	Percentage of Participants Who Experienced an AE Related to Any Type of Infection	Up to Week 52 (n=75, 63, 55, 82)	35.4 Percentage of Participants

Secondary

Percentage of Participants Who Experienced an AE Related to Respiratory Infection

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.

Time frame: Up to 26 , 52 and 104 weeks

Arm	Measure	Group	Value (NUMBER)
Navarixin 10 mg	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
Navarixin 10 mg	Percentage of Participants Who Experienced an AE Related to Respiratory Infection	Up to Week 104 (n=0, 0, 0, 0)	NA Percentage of Participants
Navarixin 10 mg	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
Navarixin 30 mg	Percentage of Participants Who Experienced an AE Related to Respiratory Infection	Up to Week 26 (n=152, 165, 152, 154)	30.1 Percentage of Participants
Navarixin 30 mg	Percentage of Participants Who Experienced an AE Related to Respiratory Infection	Up to Week 104 (n=0, 0, 0, 0)	NA Percentage of Participants
Navarixin 30 mg	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
Navarixin 50 mg	Percentage of Participants Who Experienced an AE Related to Respiratory Infection	Up to Week 52 (n=75, 63, 55, 82)	38.2 Percentage of Participants
Navarixin 50 mg	Percentage of Participants Who Experienced an AE Related to Respiratory Infection	Up to Week 26 (n=152, 165, 152, 154)	22.4 Percentage of Participants
Navarixin 50 mg	Percentage of Participants Who Experienced an AE Related to Respiratory Infection	Up to Week 104 (n=0, 0, 0, 0)	NA Percentage of Participants
Placebo	Percentage of Participants Who Experienced an AE Related to Respiratory Infection	Up to Week 26 (n=152, 165, 152, 154)	24.0 Percentage of Participants
Placebo	Percentage of Participants Who Experienced an AE Related to Respiratory Infection	Up to Week 104 (n=0, 0, 0, 0)	NA Percentage of Participants
Placebo	Percentage of Participants Who Experienced an AE Related to Respiratory Infection	Up to Week 52 (n=75, 63, 55, 82)	28.0 Percentage of Participants

Secondary

Percentage of Participants With a Moderate to Severe COPD Exacerbation

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.

Time frame: 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.

Arm	Measure	Group	Value (NUMBER)
Navarixin 10 mg	Percentage of Participants With a Moderate to Severe COPD Exacerbation	Up to Week 26 (n=152, 156, 152, 154)	26.3 Percentage of Participants
Navarixin 10 mg	Percentage of Participants With a Moderate to Severe COPD Exacerbation	Up to Week 104 (n=0, 0, 0, 0)	NA Percentage of Participants
Navarixin 10 mg	Percentage of Participants With a Moderate to Severe COPD Exacerbation	Up to Week 52 (n=152, 156, 152, 154)	32.9 Percentage of Participants
Navarixin 30 mg	Percentage of Participants With a Moderate to Severe COPD Exacerbation	Up to Week 26 (n=152, 156, 152, 154)	32.1 Percentage of Participants
Navarixin 30 mg	Percentage of Participants With a Moderate to Severe COPD Exacerbation	Up to Week 104 (n=0, 0, 0, 0)	NA Percentage of Participants
Navarixin 30 mg	Percentage of Participants With a Moderate to Severe COPD Exacerbation	Up to Week 52 (n=152, 156, 152, 154)	37.2 Percentage of Participants
Navarixin 50 mg	Percentage of Participants With a Moderate to Severe COPD Exacerbation	Up to Week 52 (n=152, 156, 152, 154)	33.6 Percentage of Participants
Navarixin 50 mg	Percentage of Participants With a Moderate to Severe COPD Exacerbation	Up to Week 26 (n=152, 156, 152, 154)	29.6 Percentage of Participants
Navarixin 50 mg	Percentage of Participants With a Moderate to Severe COPD Exacerbation	Up to Week 104 (n=0, 0, 0, 0)	NA Percentage of Participants
Placebo	Percentage of Participants With a Moderate to Severe COPD Exacerbation	Up to Week 26 (n=152, 156, 152, 154)	31.2 Percentage of Participants
Placebo	Percentage of Participants With a Moderate to Severe COPD Exacerbation	Up to Week 104 (n=0, 0, 0, 0)	NA Percentage of Participants
Placebo	Percentage of Participants With a Moderate to Severe COPD Exacerbation	Up to Week 52 (n=152, 156, 152, 154)	34.4 Percentage of Participants

Secondary

Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78)

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	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 0.43
Navarixin 10 mg	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
Navarixin 10 mg	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
Navarixin 10 mg	Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78)	Week 104 (n=0, 0, 0, 0)	NA pg/mL	—
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78)	Week 26 (n=119, 105, 92, 121)	543.60 pg/mL	Standard Deviation 0.451
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78)	Week 52 (n=42, 32, 33, 42)	603.44 pg/mL	Standard Deviation 0.409
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78)	Week 104 (n=0, 0, 0, 0)	NA pg/mL	—
Navarixin 30 mg	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 0.43
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78)	Week 52 (n=42, 32, 33, 42)	698.93 pg/mL	Standard Deviation 0.409
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78)	Week 26 (n=119, 105, 92, 121)	607.37 pg/mL	Standard Deviation 0.451
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78)	Week 104 (n=0, 0, 0, 0)	NA pg/mL	—
Navarixin 50 mg	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 0.43
Placebo	Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78)	Week 104 (n=0, 0, 0, 0)	NA pg/mL	—
Placebo	Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78)	Week 26 (n=119, 105, 92, 121)	473.10 pg/mL	Standard Deviation 0.451
Placebo	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 0.43
Placebo	Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78)	Week 52 (n=42, 32, 33, 42)	417.90 pg/mL	Standard Deviation 0.409

Secondary

Plasma Inflammatory Biomarker Levels: Fibrinogen

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	Plasma Inflammatory Biomarker Levels: Fibrinogen	Baseline (n=140, 138, 138, 143)	3.731 mg/dL	Standard Deviation 0.108
Navarixin 10 mg	Plasma Inflammatory Biomarker Levels: Fibrinogen	Week 26 (n=111, 104, 91, 121)	3.835 mg/dL	Standard Deviation 0.119
Navarixin 10 mg	Plasma Inflammatory Biomarker Levels: Fibrinogen	Week 52 (n=52, 40, 38, 58)	4.163 mg/dL	Standard Deviation 0.108
Navarixin 10 mg	Plasma Inflammatory Biomarker Levels: Fibrinogen	Week 104 (n=0, 0, 0, 0)	NA mg/dL	—
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Fibrinogen	Week 26 (n=111, 104, 91, 121)	4.027 mg/dL	Standard Deviation 0.119
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Fibrinogen	Week 52 (n=52, 40, 38, 58)	4.031 mg/dL	Standard Deviation 0.108
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Fibrinogen	Week 104 (n=0, 0, 0, 0)	NA mg/dL	—
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Fibrinogen	Baseline (n=140, 138, 138, 143)	3.731 mg/dL	Standard Deviation 0.108
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Fibrinogen	Week 52 (n=52, 40, 38, 58)	4.308 mg/dL	Standard Deviation 0.108
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Fibrinogen	Week 26 (n=111, 104, 91, 121)	4.068 mg/dL	Standard Deviation 0.119
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Fibrinogen	Week 104 (n=0, 0, 0, 0)	NA mg/dL	—
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Fibrinogen	Baseline (n=140, 138, 138, 143)	3.731 mg/dL	Standard Deviation 0.108
Placebo	Plasma Inflammatory Biomarker Levels: Fibrinogen	Week 104 (n=0, 0, 0, 0)	NA mg/dL	—
Placebo	Plasma Inflammatory Biomarker Levels: Fibrinogen	Week 26 (n=111, 104, 91, 121)	3.788 mg/dL	Standard Deviation 0.119
Placebo	Plasma Inflammatory Biomarker Levels: Fibrinogen	Baseline (n=140, 138, 138, 143)	3.731 mg/dL	Standard Deviation 0.108
Placebo	Plasma Inflammatory Biomarker Levels: Fibrinogen	Week 52 (n=52, 40, 38, 58)	3.788 mg/dL	Standard Deviation 0.108

Secondary

Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP)

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	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
Navarixin 10 mg	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
Navarixin 10 mg	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
Navarixin 10 mg	Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP)	Week 104 (n=0, 0, 0, 0)	NA mg/dL	—
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP)	Week 26 (n=121, 104, 100, 126)	3.728 mg/dL	Standard Deviation 0.443
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP)	Week 52 (n=67, 49, 43, 68)	3.871 mg/dL	Standard Deviation 0.432
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP)	Week 104 (n=0, 0, 0, 0)	NA mg/dL	—
Navarixin 30 mg	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
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP)	Week 52 (n=67, 49, 43, 68)	4.566 mg/dL	Standard Deviation 0.432
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP)	Week 26 (n=121, 104, 100, 126)	4.410 mg/dL	Standard Deviation 0.443
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP)	Week 104 (n=0, 0, 0, 0)	NA mg/dL	—
Navarixin 50 mg	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
Placebo	Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP)	Week 104 (n=0, 0, 0, 0)	NA mg/dL	—
Placebo	Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP)	Week 26 (n=121, 104, 100, 126)	2.889 mg/dL	Standard Deviation 0.443
Placebo	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
Placebo	Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP)	Week 52 (n=67, 49, 43, 68)	2.657 mg/dL	Standard Deviation 0.432

Secondary

Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)	Baseline (n=146, 145, 147, 148)	294.80 ng/mL	Standard Deviation 0.254
Navarixin 10 mg	Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 26 (n=119, 104, 97, 124)	247.63 ng/mL	Standard Deviation 0.272
Navarixin 10 mg	Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 52 (n=48, 36, 35, 47)	258.82 ng/mL	Standard Deviation 0.272
Navarixin 10 mg	Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 26 (n=119, 104, 97, 124)	216.40 ng/mL	Standard Deviation 0.272
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 52 (n=48, 36, 35, 47)	220.90 ng/mL	Standard Deviation 0.272
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)	Baseline (n=146, 145, 147, 148)	294.80 ng/mL	Standard Deviation 0.254
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 52 (n=48, 36, 35, 47)	244.67 ng/mL	Standard Deviation 0.272
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 26 (n=119, 104, 97, 124)	217.79 ng/mL	Standard Deviation 0.272
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)	Baseline (n=146, 145, 147, 148)	294.80 ng/mL	Standard Deviation 0.254
Placebo	Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Placebo	Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 26 (n=119, 104, 97, 124)	319.80 ng/mL	Standard Deviation 0.272
Placebo	Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)	Baseline (n=146, 145, 147, 148)	294.80 ng/mL	Standard Deviation 0.254
Placebo	Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 52 (n=48, 36, 35, 47)	342.46 ng/mL	Standard Deviation 0.272

Secondary

Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)	Baseline (n=146, 145, 147, 148)	169.15 ng/mL	Standard Deviation 0.386
Navarixin 10 mg	Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)	Week 26 (n=119, 104, 97, 124)	188.70 ng/mL	Standard Deviation 0.439
Navarixin 10 mg	Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)	Week 52 (n=47, 36, 35, 46)	234.42 ng/mL	Standard Deviation 0.451
Navarixin 10 mg	Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)	Week 26 (n=119, 104, 97, 124)	175.80 ng/mL	Standard Deviation 0.439
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)	Baseline (n=146, 145, 147, 148)	169.15 ng/mL	Standard Deviation 0.386
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)	Week 52 (n=47, 36, 35, 46)	196.67 ng/mL	Standard Deviation 0.451
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)	Week 52 (n=47, 36, 35, 46)	246.04 ng/mL	Standard Deviation 0.451
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)	Baseline (n=146, 145, 147, 148)	169.15 ng/mL	Standard Deviation 0.386
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)	Week 26 (n=119, 104, 97, 124)	173.16 ng/mL	Standard Deviation 0.439
Placebo	Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Placebo	Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)	Baseline (n=146, 145, 147, 148)	169.15 ng/mL	Standard Deviation 0.386
Placebo	Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)	Week 26 (n=119, 104, 97, 124)	227.72 ng/mL	Standard Deviation 0.439
Placebo	Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)	Week 52 (n=47, 36, 35, 46)	254.20 ng/mL	Standard Deviation 0.451

Secondary

Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase	Baseline (n=123, 117, 122, 121)	67.969 ng/mL	Standard Deviation 0.323
Navarixin 10 mg	Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase	Week 26 (n=118, 104, 93, 121)	63.592 ng/mL	Standard Deviation 0.341
Navarixin 10 mg	Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase	Week 52 (n=51, 41, 33, 52)	60.965 ng/mL	Standard Deviation 0.28
Navarixin 10 mg	Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase	Week 26 (n=118, 104, 93, 121)	63.680 ng/mL	Standard Deviation 0.341
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase	Week 52 (n=51, 41, 33, 52)	54.267 ng/mL	Standard Deviation 0.28
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 30 mg	Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase	Baseline (n=123, 117, 122, 121)	67.969 ng/mL	Standard Deviation 0.323
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase	Week 52 (n=51, 41, 33, 52)	64.296 ng/mL	Standard Deviation 0.28
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase	Week 26 (n=118, 104, 93, 121)	65.413 ng/mL	Standard Deviation 0.341
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 50 mg	Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase	Baseline (n=123, 117, 122, 121)	67.969 ng/mL	Standard Deviation 0.323
Placebo	Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Placebo	Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase	Week 26 (n=118, 104, 93, 121)	67.697 ng/mL	Standard Deviation 0.341
Placebo	Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase	Baseline (n=123, 117, 122, 121)	67.969 ng/mL	Standard Deviation 0.323
Placebo	Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase	Week 52 (n=51, 41, 33, 52)	57.804 ng/mL	Standard Deviation 0.28

Secondary

Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)	Baseline (n=38, 36, 48, 42)	29.736 pg/mL	Standard Deviation 0.552
Navarixin 10 mg	Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)	Week 26 (n=24, 22, 19, 21)	35.392 pg/mL	Standard Deviation 0.41
Navarixin 10 mg	Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)	Week 52 (n=0, 0, 0, 0)	NA pg/mL	—
Navarixin 10 mg	Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)	Week 104 (n=0, 0, 0, 0)	NA pg/mL	—
Navarixin 30 mg	Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)	Week 26 (n=24, 22, 19, 21)	38.471 pg/mL	Standard Deviation 0.41
Navarixin 30 mg	Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)	Week 52 (n=0, 0, 0, 0)	NA pg/mL	—
Navarixin 30 mg	Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)	Week 104 (n=0, 0, 0, 0)	NA pg/mL	—
Navarixin 30 mg	Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)	Baseline (n=38, 36, 48, 42)	29.736 pg/mL	Standard Deviation 0.552
Navarixin 50 mg	Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)	Week 52 (n=0, 0, 0, 0)	NA pg/mL	—
Navarixin 50 mg	Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)	Week 26 (n=24, 22, 19, 21)	31.693 pg/mL	Standard Deviation 0.41
Navarixin 50 mg	Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)	Week 104 (n=0, 0, 0, 0)	NA pg/mL	—
Navarixin 50 mg	Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)	Baseline (n=38, 36, 48, 42)	29.736 pg/mL	Standard Deviation 0.552
Placebo	Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)	Week 104 (n=0, 0, 0, 0)	NA pg/mL	—
Placebo	Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)	Week 26 (n=24, 22, 19, 21)	30.421 pg/mL	Standard Deviation 0.41
Placebo	Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)	Baseline (n=38, 36, 48, 42)	29.736 pg/mL	Standard Deviation 0.552
Placebo	Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)	Week 52 (n=0, 0, 0, 0)	NA pg/mL	—

Secondary

Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)	Baseline (n=39, 35, 46, 41)	720.45 ng/mL	Standard Deviation 0.773
Navarixin 10 mg	Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 26 (n=24, 22, 19, 21)	878.02 ng/mL	Standard Deviation 0.709
Navarixin 10 mg	Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 52 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 10 mg	Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 30 mg	Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 26 (n=24, 22, 19, 21)	711.90 ng/mL	Standard Deviation 0.709
Navarixin 30 mg	Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 52 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 30 mg	Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 30 mg	Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)	Baseline (n=39, 35, 46, 41)	720.45 ng/mL	Standard Deviation 0.773
Navarixin 50 mg	Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 52 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 50 mg	Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 26 (n=24, 22, 19, 21)	392.81 ng/mL	Standard Deviation 0.709
Navarixin 50 mg	Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 50 mg	Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)	Baseline (n=39, 35, 46, 41)	720.45 ng/mL	Standard Deviation 0.773
Placebo	Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Placebo	Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 26 (n=24, 22, 19, 21)	1480.1 ng/mL	Standard Deviation 0.709
Placebo	Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)	Baseline (n=39, 35, 46, 41)	720.45 ng/mL	Standard Deviation 0.773
Placebo	Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)	Week 52 (n=0, 0, 0, 0)	NA ng/mL	—

Secondary

Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)	Baseline (n=37, 36, 45, 41)	1.840 ng/mL	Standard Deviation 1.12
Navarixin 10 mg	Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)	Week 26 (n=24, 22, 19, 20)	3.243 ng/mL	Standard Deviation 1.488
Navarixin 10 mg	Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)	Week 52 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 10 mg	Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 30 mg	Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)	Week 26 (n=24, 22, 19, 20)	1.747 ng/mL	Standard Deviation 1.488
Navarixin 30 mg	Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)	Week 52 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 30 mg	Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 30 mg	Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)	Baseline (n=37, 36, 45, 41)	1.840 ng/mL	Standard Deviation 1.12
Navarixin 50 mg	Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)	Week 52 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 50 mg	Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)	Week 26 (n=24, 22, 19, 20)	0.932 ng/mL	Standard Deviation 1.488
Navarixin 50 mg	Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 50 mg	Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)	Baseline (n=37, 36, 45, 41)	1.840 ng/mL	Standard Deviation 1.12
Placebo	Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Placebo	Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)	Week 26 (n=24, 22, 19, 20)	3.656 ng/mL	Standard Deviation 1.488
Placebo	Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)	Baseline (n=37, 36, 45, 41)	1.840 ng/mL	Standard Deviation 1.12
Placebo	Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)	Week 52 (n=0, 0, 0, 0)	NA ng/mL	—

Secondary

Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase

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.

Time frame: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Navarixin 10 mg	Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase	Baseline (n=36, 34, 43, 37)	16.948 ng/mL	Standard Deviation 0.7
Navarixin 10 mg	Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase	Week 26 (n=23, 17, 19, 19)	16.785 ng/mL	Standard Deviation 0.773
Navarixin 10 mg	Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase	Week 52 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 10 mg	Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 30 mg	Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase	Week 26 (n=23, 17, 19, 19)	11.365 ng/mL	Standard Deviation 0.773
Navarixin 30 mg	Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase	Week 52 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 30 mg	Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 30 mg	Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase	Baseline (n=36, 34, 43, 37)	16.948 ng/mL	Standard Deviation 0.7
Navarixin 50 mg	Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase	Week 52 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 50 mg	Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase	Week 26 (n=23, 17, 19, 19)	19.106 ng/mL	Standard Deviation 0.773
Navarixin 50 mg	Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Navarixin 50 mg	Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase	Baseline (n=36, 34, 43, 37)	16.948 ng/mL	Standard Deviation 0.7
Placebo	Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase	Week 104 (n=0, 0, 0, 0)	NA ng/mL	—
Placebo	Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase	Week 26 (n=23, 17, 19, 19)	27.973 ng/mL	Standard Deviation 0.773
Placebo	Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase	Baseline (n=36, 34, 43, 37)	16.948 ng/mL	Standard Deviation 0.7
Placebo	Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase	Week 52 (n=0, 0, 0, 0)	NA ng/mL	—

Secondary

Total Exacerbations of Chronic Pulmonary Disease Tool-Patient-Recorded Outcome (EXACT-PRO) Questionnaire Score

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.

Time frame: 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.

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Change From Baseline in Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (Period 1)

Percentage of Participants With an Adverse Event (AE) Related to a Blood Absolute Neutrophil Count (ANC) of Less Than 1.5x10^9 Cells/L

Change From Baseline in Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Index Score

Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test)

Change From Baseline in Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity (FEF25%-75%) Test

Change From Baseline in Functional Residual Capacity (FRC)

Change From Baseline in Inspiratory Capacity (IC)

Change From Baseline in Modified Medical Research Council (MMRC) Dyspnea Score

Change From Baseline in Morning Peak Expiratory Flow (PEF)

Change From Baseline in Percent of Arterial Oxygen Saturation Measured by Pulse Oximetry Before and After the 6-Minute Walk Test

Change From Baseline in Post-bronchodilator FEV1 (Period 2)

Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)

Change From Baseline in Pre- and Post-6-Minute-Walk-Test Borg Scale Score

Change From Baseline in Pre-bronchodilator FEV1

Change From Baseline in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score

Change From Baseline in Total Lung Capacity (TLC)

Induced Sputum Absolute Neutrophil Counts

Number of Participants With a Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

Percentage of Participants Who Experienced an AE Related to Any Type of Infection

Percentage of Participants Who Experienced an AE Related to Respiratory Infection

Percentage of Participants With a Moderate to Severe COPD Exacerbation

Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78)

Plasma Inflammatory Biomarker Levels: Fibrinogen

Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP)

Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)

Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)

Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase

Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)

Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)

Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)

Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase

Total Exacerbations of Chronic Pulmonary Disease Tool-Patient-Recorded Outcome (EXACT-PRO) Questionnaire Score