Trial Outcomes & Findings for Study to Evaluate the Safety and Dose-Range of Navarixin (SCH 527123, MK-7123) in Participants With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (MK-7123-012) (NCT NCT00441701)

Results Overview

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which does not necessarily have a causal relationship with the treatment. AEs may include the onset of new illness and the exacerbation of pre-existing conditions. The number of participants who experienced an AE, regardless of causality or severity, was summarized.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

99 participants

Primary outcome timeframe

Up to 12 weeks

Results posted on

2019-01-02

Participant Flow

Participant milestones

Participant milestones
Measure	Part 1: Navarixin 3 mg Cohort 1: Participants receive navarixin 3 mg (three 1 mg capsules) once daily (QD) for up to 12 weeks	Part 1: Placebo to Navarixin 3 mg Cohort 1: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks	Part 1: Navarixin 10 mg Cohort 2: Participants receive navarixin 10 mg (one 10 mg capsule and two placebo capsules) QD for up to 12 weeks	Part 1: Placebo to Navarixin 10 mg Cohort 2: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks	Part 1: Navarixin 30 mg Cohort 3: Participants receive navarixin 30 mg (three 10 mg capsules) QD for up to 12 weeks	Part 1: Placebo to Navarixin 30 mg Cohort 3: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks
Overall Study STARTED	22	11	22	11	22	11
Overall Study COMPLETED	17	7	18	8	20	8
Overall Study NOT COMPLETED	5	4	4	3	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: Navarixin 3 mg Cohort 1: Participants receive navarixin 3 mg (three 1 mg capsules) once daily (QD) for up to 12 weeks	Part 1: Placebo to Navarixin 3 mg Cohort 1: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks	Part 1: Navarixin 10 mg Cohort 2: Participants receive navarixin 10 mg (one 10 mg capsule and two placebo capsules) QD for up to 12 weeks	Part 1: Placebo to Navarixin 10 mg Cohort 2: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks	Part 1: Navarixin 30 mg Cohort 3: Participants receive navarixin 30 mg (three 10 mg capsules) QD for up to 12 weeks	Part 1: Placebo to Navarixin 30 mg Cohort 3: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks
Overall Study Adverse Event	3	2	1	0	2	2
Overall Study Lack of Efficacy	2	0	2	2	0	1
Overall Study Withdrawal by Subject	0	2	1	1	0	0

Baseline Characteristics

Study to Evaluate the Safety and Dose-Range of Navarixin (SCH 527123, MK-7123) in Participants With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (MK-7123-012)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: Navarixin 3 mg n=22 Participants Cohort 1: Participants receive navarixin 3 mg (three 1 mg capsules) QD for up to 12 weeks	Part 1: Placebo to Navarixin 3 mg n=11 Participants Cohort 1: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks	Part 1: Navarixin 10 mg n=22 Participants Cohort 2: Participants receive navarixin 10 mg (one 10 mg capsule and two placebo capsules) QD for up to 12 weeks	Part 1: Placebo to Navarixin 10 mg n=11 Participants Cohort 2: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks	Part 1: Navarixin 30 mg n=22 Participants Cohort 3: Participants receive navarixin 30 mg (three 10 mg capsules) QD for up to 12 weeks	Part 1: Placebo to Navarixin 30 mg n=11 Participants Cohort 3: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks	Part 2: Navarixin 3 mg Cohort 4: Participants receive navarixin 3 mg (three 1 mg capsules) QD for up to 12 weeks	Part 2: Navarixin 10 mg Cohort 4: Participants receive navarixin 10 mg (one 10 mg capsule and two placebo capsules) QD for up to 12 weeks	Part 2: Navarixin 30 mg Cohort 4: Participants receive navarixin 30 mg (three 10 mg capsules) QD for up to 12 weeks	Part 2: Placebo to Navarixin Cohort 4: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks	Total n=99 Participants Total of all reporting groups
Age, Continuous	54.7 Years STANDARD_DEVIATION 5.5 • n=5 Participants	57.2 Years STANDARD_DEVIATION 8.6 • n=7 Participants	61.8 Years STANDARD_DEVIATION 7.3 • n=5 Participants	60.2 Years STANDARD_DEVIATION 7.8 • n=4 Participants	56.1 Years STANDARD_DEVIATION 7.8 • n=21 Participants	58.3 Years STANDARD_DEVIATION 9.4 • n=8 Participants	—	—	—	—	57.9 Years STANDARD_DEVIATION 7.8 • n=42 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	4 Participants n=4 Participants	8 Participants n=21 Participants	3 Participants n=8 Participants	—	—	—	—	37 Participants n=42 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants	7 Participants n=4 Participants	14 Participants n=21 Participants	8 Participants n=8 Participants	—	—	—	—	62 Participants n=42 Participants

PRIMARY outcome

Timeframe: Up to 12 weeks

Population: The population consisted of all Part 1 participants who were randomized and received at least one dose of study drug.

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which does not necessarily have a causal relationship with the treatment. AEs may include the onset of new illness and the exacerbation of pre-existing conditions. The number of participants who experienced an AE, regardless of causality or severity, was summarized.

Outcome measures

Outcome measures
Measure	Part 1: Navarixin 3 mg n=22 Participants Cohort 1: Participants receive navarixin 3 mg (three 1 mg capsules) QD for up to 12 weeks	Part 1: Navarixin 10 mg n=22 Participants Cohort 2: Participants receive navarixin 10 mg (one 10 mg capsule and two placebo capsules) QD for up to 12 weeks	Part 1: Navarixin 30 mg n=22 Participants Cohort 3: Participants receive navarixin 30 mg (three 10 mg capsules) QD for up to 12 weeks	Part 1: Placebo to Navarixin (Pooled) n=33 Participants Pooled Placebo Cohorts: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks
Part 1: Number of Participants Who Experience at Least One Adverse Event (AE)	10 Participants	12 Participants	12 Participants	20 Participants

PRIMARY outcome

Timeframe: Up to 12 weeks

Population: The population consisted of all Part 1 participants who were randomized and received at least one dose of study drug.

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which does not necessarily have a causal relationship with the treatment. AEs may include the onset of new illness and the exacerbation of pre-existing conditions. The number of participants who discontinued study drug, whether permanently or temporarily, due to an AE was summarized.

Outcome measures

Outcome measures
Measure	Part 1: Navarixin 3 mg n=22 Participants Cohort 1: Participants receive navarixin 3 mg (three 1 mg capsules) QD for up to 12 weeks	Part 1: Navarixin 10 mg n=22 Participants Cohort 2: Participants receive navarixin 10 mg (one 10 mg capsule and two placebo capsules) QD for up to 12 weeks	Part 1: Navarixin 30 mg n=22 Participants Cohort 3: Participants receive navarixin 30 mg (three 10 mg capsules) QD for up to 12 weeks	Part 1: Placebo to Navarixin (Pooled) n=33 Participants Pooled Placebo Cohorts: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks
Part 1: Number of Participants Who Discontinue Study Drug Due to an AE	3 Participants	1 Participants	2 Participants	4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: The population consisted of all Part 1 participants who were randomized and received at least one dose of study drug and had a Baseline and a Week 12 assessment for absolute PBN count.

Participants were assessed for absolute PBN counts at Baseline and Week 12. The reported standard deviations (SDs) are pooled across all treatment groups. The rationale for the use of an analysis of variance (ANOVA) method using pooled SD values is the assumption that the SDs are similar across treatment groups.

Outcome measures

Outcome measures
Measure	Part 1: Navarixin 3 mg n=17 Participants Cohort 1: Participants receive navarixin 3 mg (three 1 mg capsules) QD for up to 12 weeks	Part 1: Navarixin 10 mg n=19 Participants Cohort 2: Participants receive navarixin 10 mg (one 10 mg capsule and two placebo capsules) QD for up to 12 weeks	Part 1: Navarixin 30 mg n=20 Participants Cohort 3: Participants receive navarixin 30 mg (three 10 mg capsules) QD for up to 12 weeks	Part 1: Placebo to Navarixin (Pooled) n=24 Participants Pooled Placebo Cohorts: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks
Part 1: Change From Baseline in Absolute Peripheral Blood Neutrophil (PBN) Count	-0.33 10^9 cells/L Standard Deviation 1.67	-1.06 10^9 cells/L Standard Deviation 1.67	-0.56 10^9 cells/L Standard Deviation 1.67	0.06 10^9 cells/L Standard Deviation 1.67

PRIMARY outcome

Timeframe: Baseline and the Average over 12 weeks

Population: The population was to consist of all Part 2 participants who were randomized, received at least one dose of study drug, and had a Baseline and at least one post-Baseline assessment for FEV1. Part 2 of this study was not conducted under this protocol.

FEV1, as measured in liters via spirometry, is a measure of the amount of air expired in 1 second. Participants were to be assessed for pre-bronchodilator FEV1 immediately before dosing with bronchodilator (albuterol sulfate or equivalent) at Baseline and at Week 12. Pre-bronchodilator FEV1 data were to be averaged weekly over the 12-week treatment period for analysis.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline and the Average over 12 weeks

Population: The population was to consist of all Part 2 participants who were randomized, received at least one dose of study drug, and had a Baseline and at least one post-Baseline assessment for AM/PM SCDS scores. Part 2 of this study was not conducted under this protocol.

Participants were to assess their morning (AM) and nighttime (PM) COPD symptoms (sputum production, cough, and dyspnea) on a daily basis in their e-Diaries. Baseline SCDS was defined as the average of AM and PM values over the week prior to and including Day 1 (AM) prior to the first dose of study drug. SCDS data were to be averaged weekly over the 12-week treatment period for analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The population was to consist of all Part 1 participants who were randomized, received at least one dose of study drug, and had a Baseline and a Week 12 assessment for percent PBN count. Since sufficient data for analysis were collected for absolute PBN count, percent PBN count was not assessed.

Participants were to be assessed for percent PBN counts at Baseline and at Week 12.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The population consisted of all Part 1 participants who were randomized, received at least one dose of study drug, and had a Baseline and Week 12 assessment for induced sputum absolute neutrophil count.

Participants were assessed for induced sputum absolute neutrophil counts via the nebulized method at Baseline and at Week 12. The reported SDs are pooled across all treatment groups. The rationale for the use of an ANOVA method using pooled SD values is the assumption that the SDs are similar across treatment groups.

Outcome measures

Outcome measures
Measure	Part 1: Navarixin 3 mg n=12 Participants Cohort 1: Participants receive navarixin 3 mg (three 1 mg capsules) QD for up to 12 weeks	Part 1: Navarixin 10 mg n=18 Participants Cohort 2: Participants receive navarixin 10 mg (one 10 mg capsule and two placebo capsules) QD for up to 12 weeks	Part 1: Navarixin 30 mg n=18 Participants Cohort 3: Participants receive navarixin 30 mg (three 10 mg capsules) QD for up to 12 weeks	Part 1: Placebo to Navarixin (Pooled) n=20 Participants Pooled Placebo Cohorts: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks
Part 1: Change From Baseline in Sputum Absolute Neutrophil Count (Induced Sputum)	-1.30 10^9 cells/L Standard Deviation 7.83	-0.84 10^9 cells/L Standard Deviation 7.83	-4.04 10^9 cells/L Standard Deviation 7.83	-0.22 10^9 cells/L Standard Deviation 7.83

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The population was to consist of all Part 1 participants who were randomized, received at least 1 dose of study drug, and had a Baseline and Week 12 assessment for sputum percent neutrophil count. Since sufficient data for analysis were collected for absolute sputum neutrophil count, percent sputum neutrophil count was not assessed.

Sputum neutrophils were to be measured as percent of total white blood cells. Participants were to be assessed for induced sputum percent neutrophil counts via the nebulized method at Baseline and at Week 12.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and the Average over 12 weeks

Population: The population was to consist of all Part 2 participants who were randomized, received at least one dose of study drug, and had a Baseline and Week 12 efficacy assessment for post-bronchodilator FEV1. Part 2 of this study was not conducted under this protocol.

FEV1, as measured in liters via spirometry, is a measure of the amount of air expired in 1 second. Participants were to be assessed for post-bronchodilator FEV1 30 minutes after dosing with bronchodilator (albuterol sulfate or equivalent) (reversibility test) at Baseline and Week 12. Post-bronchodilator data were to be averaged weekly over the 12-week treatment period for analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The population was to consist of all Part 2 participants who were randomized, received at least one dose of study drug, and had a Baseline and Week 12 assessment for FEF25%-75%. Part 2 of this study was not conducted under this protocol.

Mid-Breath Forced Expiratory Flow (FEF25%-75%), as measured in liters/minute via spirometry, is the rate at which participants breathe out air from 25 percent of their breath to 75 percent of their breath. Participants were to be assessed for FEF25%-75% at Baseline and Week 12.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The population was to consist of all Part 2 participants who were randomized, received at least one dose of study drug, and had a Baseline and Week 12 efficacy assessment for FVC. Part 2 of this study was not conducted under this protocol.

FVC, as measured in liters via 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 at Baseline and Week 12.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The population was to consist of all Part 2 participants who were randomized, received at least one dose of study drug, and had a Baseline and Week 12 efficacy assessment for FRC. Part 2 of this study was not conducted under this protocol.

FRC, as measured in liters via body plethysmography, is the volume of air present in the lungs, specifically the parenchyma tissues, at the end of passive expiration. Participants were to be assessed for FRC at Baseline and Week 12.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Week 12

Population: The population was to consist of all Part 2 participants who were randomized, received at least one dose of study drug, and had a at least one post-Baseline assessment for presence of COPD exacerbation. Part 2 of this study was not conducted under this protocol.

COPD exacerbation is defined as any change in symptoms or functional status that leads to administration of systemic corticosteroids, antibiotics, an emergency room visit or a hospitalization. The number of participants who experienced a COPD exacerbation was to be summarized.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The population was to consist of all Part 2 participants who were randomized, received at least one dose of study drug, and had a Baseline and Week 12 efficacy assessment for PEF. Part 2 of this study was not conducted under this protocol.

PEF, as measured in liters/minute via peak flow meter, is the maximum speed of expiration. Participants were to measure their PEF in triplicate every morning before taking study drug and again every evening.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The population was to consist of all Part 2 participants who were randomized, received at least one dose of study drug and had a Baseline and Week 12 assessment for induced sputum absolute neutrophil count. Part 2 of this study was not conducted under this protocol.

Participants were to be assessed for induced sputum absolute neutrophil counts via the nebulized method at Baseline and at Week 12.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The population was to consist of all Part 2 participants who were randomized, received at least one dose of study drug and had a Baseline and Week 12 assessment for sputum percent neutrophil count. Part 2 of this study was not conducted under this protocol.

Sputum neutrophils were to be measured as percent of total white blood cells. Participants were to be assessed for induced sputum percent neutrophil counts via the nebulized method at Baseline and at Week 12.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The population was to consist of all Part 2 participants who were randomized, received at least one dose of study drug and had a Baseline and Week 12 efficacy assessment for individual symptom scores. Part 2 of this study was not conducted under this protocol.

Participants were to be assessed for individual symptom scores at Baseline and Week 12 using the following scales: Sputum Production (0=none, unaware of any sputum production to 4=severe, an almost constant problem), Cough (0=none, unaware of coughing to 4=severe, never free of cough or need to cough), and Dyspnea (0=none, unaware of any difficulty to 4=severe, almost constant: present even when resting).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The population was to consist of all Part 2 participants who were randomized, received at least one dose of study drug and had a Baseline and Week 12 efficacy assessment for SGRQ. Part 2 of this study was not conducted under this protocol.

SGRQ consists of 76 items aggregated into 3 domain scores: Symptoms (frequency/severity), Activity (cause or limited by breathlessness), Impact (social functioning, psychological disturbances from airway disease), and total score. Participants were to assess their symptoms, activity and impact at Baseline and Week 12.

Outcome measures

Outcome data not reported

Adverse Events

Part 1: Navarixin 3 mg

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Part 1: Navarixin 10 mg

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Part 1: Navarixin 30 mg

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Part 1: Placebo to Navarixin (Pooled)

Serious events: 4 serious events

Other events: 10 other events

Deaths: 0 deaths

Part 2: Navarixin 3 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part 2: Navarixin 10 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part 2: Navarixin 30 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part 2: Placebo to Navarixin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part 1: Navarixin 3 mg n=22 participants at risk Cohort 1: Participants receive navarixin 3 mg (three 1 mg capsules) QD for up to 12 weeks	Part 1: Navarixin 10 mg n=22 participants at risk Cohort 2: Participants receive navarixin 10 mg (one 10 mg capsule and two placebo capsules) QD for up to 12 weeks	Part 1: Navarixin 30 mg n=22 participants at risk Cohort 3: Participants receive navarixin 30 mg (three 10 mg capsules) QD for up to 12 weeks	Part 1: Placebo to Navarixin (Pooled) n=33 participants at risk Pooled Placebo Cohorts: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks	Part 2: Navarixin 3 mg Cohort 4: Participants receive navarixin 3 mg (three 1 mg capsules) QD for up to 12 weeks	Part 2: Navarixin 10 mg Cohort 4: Participants receive navarixin 10 mg (one 10 mg capsule and two placebo capsules) QD for up to 12 weeks	Part 2: Navarixin 30 mg Cohort 4: Participants receive navarixin 30 mg (three 10 mg capsules) QD for up to 12 weeks	Part 2: Placebo to Navarixin Cohort 4: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks
Cardiac disorders Congestive cardiomyopathy	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	3.0% 1/33 • Number of events 1 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.
Cardiac disorders Left ventricular failure	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	3.0% 1/33 • Number of events 1 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.
Cardiac disorders Myocardial infarction	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	4.5% 1/22 • Number of events 1 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	4.5% 1/22 • Number of events 1 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/33 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.
Injury, poisoning and procedural complications Fall	4.5% 1/22 • Number of events 1 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/33 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenoma	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	3.0% 1/33 • Number of events 1 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.
Nervous system disorders Cerebrovascular accident	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	3.0% 1/33 • Number of events 1 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.
Psychiatric disorders Alcohol abuse	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	3.0% 1/33 • Number of events 1 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	3.0% 1/33 • Number of events 1 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.

Other adverse events

Other adverse events
Measure	Part 1: Navarixin 3 mg n=22 participants at risk Cohort 1: Participants receive navarixin 3 mg (three 1 mg capsules) QD for up to 12 weeks	Part 1: Navarixin 10 mg n=22 participants at risk Cohort 2: Participants receive navarixin 10 mg (one 10 mg capsule and two placebo capsules) QD for up to 12 weeks	Part 1: Navarixin 30 mg n=22 participants at risk Cohort 3: Participants receive navarixin 30 mg (three 10 mg capsules) QD for up to 12 weeks	Part 1: Placebo to Navarixin (Pooled) n=33 participants at risk Pooled Placebo Cohorts: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks	Part 2: Navarixin 3 mg Cohort 4: Participants receive navarixin 3 mg (three 1 mg capsules) QD for up to 12 weeks	Part 2: Navarixin 10 mg Cohort 4: Participants receive navarixin 10 mg (one 10 mg capsule and two placebo capsules) QD for up to 12 weeks	Part 2: Navarixin 30 mg Cohort 4: Participants receive navarixin 30 mg (three 10 mg capsules) QD for up to 12 weeks	Part 2: Placebo to Navarixin Cohort 4: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks
Gastrointestinal disorders Toothache	4.5% 1/22 • Number of events 1 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	9.1% 2/22 • Number of events 2 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/33 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.
Infections and infestations Nasopharyngitis	22.7% 5/22 • Number of events 5 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	31.8% 7/22 • Number of events 8 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	27.3% 6/22 • Number of events 7 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	15.2% 5/33 • Number of events 5 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.
Infections and infestations Rhinitis	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	4.5% 1/22 • Number of events 1 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	4.5% 1/22 • Number of events 1 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	6.1% 2/33 • Number of events 2 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.
Nervous system disorders Headache	4.5% 1/22 • Number of events 1 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	4.5% 1/22 • Number of events 3 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	4.5% 1/22 • Number of events 1 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	6.1% 2/33 • Number of events 2 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.
Respiratory, thoracic and mediastinal disorders Dysphonia	9.1% 2/22 • Number of events 2 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	3.0% 1/33 • Number of events 1 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	9.1% 2/22 • Number of events 2 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/33 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.
Vascular disorders Hypertension	4.5% 1/22 • Number of events 1 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	0.00% 0/22 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	6.1% 2/33 • Number of events 2 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.	— 0/0 • Up to 30 days after last dose of study drug (Up to 16 weeks) Part 2 was not conducted under this protocol.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator agrees to provide the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication (including, without limitation, slides and texts of oral or other public presentations and texts of any transmission through any electronic media, eg, any computer access system such as the Internet, World Wide Web, etc.) that report any results of the study.
Publication restrictions are in place

Restriction type: OTHER