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

NCT01006616 | Terminated Phase 2 Results DMC

• 2 other identifiers: P055752008-003780-38
• Study Type: interventional
• Target: 616
• Locations: 0 countries
• Sites: N/A

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.

Conditions

COPD

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  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.

  Up to 104 weeks

Secondary Outcomes (30)

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

  Baseline and Week 52, Week 104

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

  Up to 26 , 52 and 104 weeks

• Percentage of Participants With a Moderate to Severe COPD Exacerbation

  Up to 26, 52 and 104 weeks

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

  At 26, 52 and 104 weeks

• Induced Sputum Absolute Neutrophil Counts

  Baseline, Week 26, Week 52, Week 104

Study Arms (4)

Navarixin 10 mg

EXPERIMENTAL

Participants receive navarixin 10 mg, as one navarixin 10 mg capsule and two placebo capsules, administered orally once daily (QD) for up to 2 years

Drug: Navarixin; Drug: Placebo; Drug: Rescue medication

Navarixin 30 mg

EXPERIMENTAL

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

Drug: Navarixin; Drug: Placebo; Drug: Rescue medication

Navarixin 50 mg

EXPERIMENTAL

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

Drug: Navarixin; Drug: Rescue medication

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo; Drug: Rescue medication

Interventions

Navarixin DRUG

Navarixin 10 mg and 30 mg capsules

Navarixin 10 mg; Navarixin 30 mg; Navarixin 50 mg

Placebo DRUG

Placebo to navarixin capsules

Navarixin 10 mg; Navarixin 30 mg; Placebo

Rescue medication DRUG

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

Navarixin 10 mg; Navarixin 30 mg; Navarixin 50 mg; Placebo

Eligibility Criteria

• Age: 41 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Rennard SI, Dale DC, Donohue JF, Kanniess F, Magnussen H, Sutherland ER, Watz H, Lu S, Stryszak P, Rosenberg E, Staudinger H. CXCR2 Antagonist MK-7123. A Phase 2 Proof-of-Concept Trial for Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2015 May 1;191(9):1001-11. doi: 10.1164/rccm.201405-0992OC.

  PMID: 25695403 RESULT

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

navarixin

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2009
• First Posted: November 3, 2009
• Study Start: October 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: November 1, 2011
• Last Updated: January 2, 2019
• Results First Posted: November 17, 2014

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will share