NCT00441701

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)

Terminated Phase 2 Results posted Last updated 2 January 2019

What this trial tests

Phase 2 trial testing Navarixin 1 mg in Chronic Obstructive Pulmonary Disease in 99 participants. Terminated before completion.

Timeline

1 December 2006

Primary endpoint
1 October 2008

1 October 2008

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	99
Start date	1 December 2006
Primary completion	1 October 2008
Estimated completion	1 October 2008

Drugs / interventions tested

• Navarixin 1 mg — full drug profile →
• Navarixin 10 mg — full drug profile →
• Placebo to match navarixin — full drug profile →
• Rescue medication — full drug profile →

Conditions studied

• Chronic Obstructive Pulmonary Disease — all drugs for Chronic Obstructive Pulmonary Disease →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 41 to 75, any sex, with Chronic Obstructive Pulmonary Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Part 1: Number of Participants Who Experience at Least One Adverse Event (AE) Primary · Up to 12 weeks

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.

Group	Value	95% CI
Part 1: Navarixin 3 mg	10
Part 1: Navarixin 10 mg	12
Part 1: Navarixin 30 mg	12
Part 1: Placebo to Navarixin (Pooled)	20

Part 1: Number of Participants Who Discontinue Study Drug Due to an AE Primary · Up to 12 weeks

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.

Group	Value	95% CI
Part 1: Navarixin 3 mg	3
Part 1: Navarixin 10 mg	1
Part 1: Navarixin 30 mg	2
Part 1: Placebo to Navarixin (Pooled)	4

Part 1: Change From Baseline in Absolute Peripheral Blood Neutrophil (PBN) Count Primary · Baseline and Week 12

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.

Group	Value	95% CI
Part 1: Navarixin 3 mg	-0.33	± 1.67
Part 1: Navarixin 10 mg	-1.06	± 1.67
Part 1: Navarixin 30 mg	-0.56	± 1.67
Part 1: Placebo to Navarixin (Pooled)	0.06	± 1.67

Part 1: Change From Baseline in Sputum Absolute Neutrophil Count (Induced Sputum) Secondary · Baseline and Week 12

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.

Group	Value	95% CI
Part 1: Navarixin 3 mg	-1.30	± 7.83
Part 1: Navarixin 10 mg	-0.84	± 7.83
Part 1: Navarixin 30 mg	-4.04	± 7.83
Part 1: Placebo to Navarixin (Pooled)	-0.22	± 7.83

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 30 days after last dose of study drug (Up to 16 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part 1: Navarixin 3 mg

Serious: 1/22 (5%)

Deaths: —

Part 1: Navarixin 10 mg

Serious: 1/22 (5%)

Deaths: —

Part 1: Navarixin 30 mg

Serious: 1/22 (5%)

Deaths: —

Part 1: Placebo to Navarixin (Pooled)

Serious: 4/33 (12%)

Deaths: —

Part 2: Navarixin 3 mg

Serious: 0

Deaths: —

Part 2: Navarixin 10 mg

Serious: 0

Deaths: —

Part 2: Navarixin 30 mg

Serious: 0

Deaths: —

Part 2: Placebo to Navarixin

Serious: 0

Deaths: —

Serious adverse events (8 terms)

Reaction	System	Part 1: Navarixin 3 mg	Part 1: Navarixin 10 mg	Part 1: Navarixin 30 mg	Part 1: Placebo to Navarix…	Part 2: Navarixin 3 mg	Part 2: Navarixin 10 mg	Part 2: Navarixin 30 mg	Part 2: Placebo to Navarixin
Congestive cardiomyopathy	Cardiac disorders	—	—	—	—	—	—	—	—
Left ventricular failure	Cardiac disorders	—	—	—	—	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—	—	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—
Rectal adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—
Cerebrovascular accident	Nervous system disorders	—	—	—	—	—	—	—	—
Alcohol abuse	Psychiatric disorders	—	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—

Other adverse events (7 terms — click to expand)

Reaction	System	Part 1: Navarixin 3 mg	Part 1: Navarixin 10 mg	Part 1: Navarixin 30 mg	Part 1: Placebo to Navarix…	Part 2: Navarixin 3 mg	Part 2: Navarixin 10 mg	Part 2: Navarixin 30 mg	Part 2: Placebo to Navarixin
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—	—	—
Toothache	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Rhinitis	Infections and infestations	—	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—	—
Dysphonia	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—	—	—	—	—

Most-reported serious reactions: Congestive cardiomyopathy, Left ventricular failure, Myocardial infarction, Fall, Rectal adenoma, Cerebrovascular accident, Alcohol abuse, Dyspnoea.

Data from ClinicalTrials.gov NCT00441701 adverse events section.

Sponsor's own description

This is a two-part study conducted at multiple centers, of navarixin (SCH 527123, MK-7123) in participants with moderate to severe chronic obstructive pulmonary disease (COPD). Part 1 of the study is a double-blind, placebo-controlled, randomized, rising-dose study consisting of four treatment groups enrolled in three cohorts. The duration of treatment, for each cohort, will be a 2-week run-in period, followed by a 12-week double-blind treatment period. Treatment initiation for each cohort was staggered by 4 weeks to allow for safety assessment prior to use of higher doses of navarixin. Part 2 of the study will be a double-blind, placebo-controlled, randomized, parallel group study consisting of four treatment groups enrolled as one cohort. The duration of treatment will consist of a 2-week run-in period, followed by a 12-week double-blind treatment period.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Progress in the mechanism and targeted drug therapy for COPD.
   Wang C, Zhou J, Wang J, Li S, et al · · 2020 · cited 214× · PMID 33110061 · DOI 10.1038/s41392-020-00345-x
2. Wound healing and cancer stem cells: inflammation as a driver of treatment resistance in breast cancer.
   Arnold KM, Opdenaker LM, Flynn D, Sims-Mourtada J. · · 2015 · cited 84× · PMID 25674014 · DOI 10.4137/cgm.s11286
3. Significance of the IL-8 pathway for immunotherapy.
   Gonzalez-Aparicio M, Alfaro C. · · 2020 · cited 37× · PMID 31860375 · DOI 10.1080/21645515.2019.1696075
4. Emerging pharmaceutical therapies for COPD.
   Lakshmi SP, Reddy AT, Reddy RC. · · 2017 · cited 35× · PMID 28790817 · DOI 10.2147/copd.s121416
5. Inhaled RNA Therapeutics for Obstructive Airway Diseases: Recent Advances and Future Prospects.
   Xu Y, Thakur A, Zhang Y, Foged C. · · 2021 · cited 24× · PMID 33525500 · DOI 10.3390/pharmaceutics13020177
6. The CXCL1-CXCR2 Axis as a Component of Therapy Resistance, a Source of Side Effects in Cancer Treatment, and a Therapeutic Target.
   Korbecki J, Bosiacki M, Pilarczyk M, Kot M, et al · · 2025 · cited 11× · PMID 40427171 · DOI 10.3390/cancers17101674
7. The Molecular Blueprint for Chronic Obstructive Pulmonary Disease (COPD): A New Paradigm for Diagnosis and Therapeutics.
   Shakeel I, Ashraf A, Afzal M, Sohal SS, et al · · 2023 · cited 10× · PMID 38155869 · DOI 10.1155/2023/2297559