Neutrophilic Asthma Study With Navarixin (MK-7123, SCH 527123) (MK-7123-017)(COMPLETED)

Safety of SCH 527123 in Subjects With Neutrophilic Asthma

4-Week Safety Study in Subjects with Neutrophilic Asthma

Study Overview

• Status: Completed
• Conditions: Neutrophilic Asthma
• Intervention / Treatment: Drug: Navarixin; Drug: Rescue medication; Drug: Placebo

Detailed Description

Effect of treatment with navarixin (MK-7123, SCH 527123) on sputum neutrophils and asthma symptoms

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 to <=70 years of age, either sex, any race.
• Induced sputum neutrophil count >=40% of total white blood cells and <10 million/mL at Screening.
• Documented diagnosis of asthma (within past 5 years), determined by at least one of the following: >=12% and 200 mL improvement in Forced Expiratory Volume in 1 second (FEV1) post-bronchodilator, and/or airway hyperresponsiveness (eg, positive methacholine challenge <8 mg/mL).
• Nonsmoker or previous smoker with cumulative smoking history less than 20 pack-years (pack-year = 20 cigarettes smoked daily for 1 year). Previous smokers may not have smoked within 1 year prior to Screening.
• Must not have had an exacerbation of asthma for 4 weeks prior to Screening and must be on a stable medication regimen for asthma at least 4 weeks prior to Screening.
• Must be receiving >=800 mcg/day of beclomethasone dipropionate (BDP) or equivalent for at least 3 months prior to Screening (and on stable dose for at least 4 weeks prior to Screening).
• Must be willing to give written informed consent to participate in the study
• Must be capable of complying with the dosing regimen, adhere to the visit schedule, and participate in all treatment procedures, including sputum induction.
• Female subject of childbearing potential must have a negative serum pregnancy test at Screening and must be using a medically acceptable, highly effective, adequate form of birth control (ie, failure rate <1% per year when used consistently and correctly) prior to Screening and agree to continue using it while in the study (Screening and Treatment Periods). Medically acceptable, highly effective forms of birth control are hormonal implants, oral contraceptives, medically acceptable prescribed intrauterine devices (IUDs), and monogamous relationship with a male partner who has had a vasectomy. Female subject who is not of childbearing potential must have a medical record of being surgically sterile (eg, hysterectomy, tubal ligation), or be at least 1 year postmenopausal. Absence of menses for at least 1 year will indicate that a female is postmenopausal. A female subject should be encouraged to continue using a highly effective method of birth control for 30 days following the end of treatment.
• Male subject must agree to use an adequate form of contraception for the duration of the study and agree to have sexual relations only with women who use a highly effective birth control method.

Exclusion Criteria:

• Chronic Obstructive Pulmonary Disease (COPD)/other relevant lung disease (other than asthma).
• 4 weeks prior to/or Screening: upper/lower respiratory tract infection.
• Prohibited medications received more recently than indicated washout prior to Screening
• Screening: Inadequate amount or difficulty producing sputum.
• Screening: Sputum neutrophil count over 10 million/mL.
• Screening: peripheral blood neutrophil (PBN) count <3000/µL.
• Post-bronchodilator FEV1 <1L.
• Clinically significant chronic infectious disease(s) (eg, Human Immunodeficiency Virus [HIV], hepatitis B or C).
• Allergy/sensitivity to study drug/excipients.
• Breast-feeding, pregnant/intends to become pregnant during study.
• Requiring mechanical ventilation for respiratory event within 6 months of Screening.
• Medical condition(s) (eg, hematologic, cardiovascular, renal, hepatic, neurologic, or metabolic) or medication that may interfere with effect of study medication.
• Within 30 days of Screening: any other investigational drug.
• Participation in any other clinical study.
• Part of the staff personnel involved with the study.
• Family member of investigational study staff.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Navarixin; Navarixin (MK-7123, SCH 527123) 30 mg capsule, to be taken by mouth once daily in the morning for 4 weeks	Drug: Navarixin; Navarixin 30 mg capsule to be taken by mouth once daily in the morning for 4 weeks.; Drug: Rescue medication; Participant choice of short-acting beta-2 agonist (salbutamol/albuterol), anticholinergic, or combination medication as needed for asthma symptoms
Placebo Comparator: Placebo; Placebo capsule to match navarixin, to be taken by mouth once daily in the morning for 4 weeks	Drug: Rescue medication; Participant choice of short-acting beta-2 agonist (salbutamol/albuterol), anticholinergic, or combination medication as needed for asthma symptoms; Drug: Placebo; Placebo capsule to match navarixin to be taken by mouth once daily in the morning for 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Maintained an Absolute Peripheral Blood Neutrophil Count >=1500/µL	Peripheral blood neutrophil counts were performed on Day 2 and Weeks 1, 2, 3, and 4 of the treatment period	Up to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Sputum Absolute Neutrophil Count	Induced sputum samples were obtained at Baseline and at Weeks 2 and 4 of the treatment period. Samples were collected before study drug administration using the nebulizer method and sent to a central laboratory for analysis. An average was taken over all post-baseline samples collected no later than one day after the last dose of study drug.	Baseline and while on study drug (up to 4 weeks)
Mean Change From Baseline in Total Asthma Symptom Score	Total Asthma Symptom Score is the sum of individual symptoms of wheezing, coughing, and dyspnea assessed twice daily (morning and evening) and is recorded on a comment diary card. Each of the symptoms receives a daily score from 0 (none) to 3 (severe), averaged over the two daily assessments. The total score ranges from 0 to 9, with a lower score indicating less severe asthma symptoms.	Baseline and Weeks 1, 2, 3, and 4
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1)	Spirometry was used to measure post-bronchodilator FEV1 at Baseline and before study drug administration at Weeks 1, 2, 3, and 4. Participants received 4 puffs of bronchodilator (salbutamol hydrofluoroalkane or equivalent) at 30-second intervals and spirometry was performed 30 minutes later. The mean change from baseline is based on the average change over all post-baseline assessments.	Baseline and up to 4 weeks
Change From Baseline in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ[S])	The AQLQ[S] was administered at Baseline and at Weeks 2 and 4. The assessment consists of a 32-item questionnaire covering 4 domains: symptoms, emotional functioning, impact of environmental stimuli, and activity limitation. Each item receives a score from 1 (worst, or most affected) to 7 (not at all affected). The score is the mean across all items, and ranges from 1 to 7. The mean change from baseline is based on the average change over all post-baseline assessments.	Baseline and up to 4 weeks
Number of Participants With an Adverse Event (AE)	An AE is any untoward medical occurrence in a participant administered study drug 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.	Up to 5 weeks
Number of Participants With an Electrocardiogram Adverse Event	The endpoint measured was any electrocardiogram abnormality that was reported as an AE. An AE is any untoward medical occurrence in a participant administered study drug 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.	Week 4
Number of Participants With a Laboratory Adverse Event	The endpoint measured was any laboratory (hematology, blood chemistry, or urinalysis) abnormality that was reported as an AE. An AE is any untoward medical occurrence in a participant administered study drug 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.	Up to 5 weeks
Number of Participants Who Discontinued the Study Because of an Adverse Event	An AE is any untoward medical occurrence in a participant administered study drug 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.	Up to 5 weeks
Number of Participants Who Discontinued Treatment Because of an Adverse Event or a Protocol-defined Clinical Event	An AE is any untoward medical occurrence in a participant administered study drug 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. A protocol-defined clinical event is an asthma exacerbation requiring addition of or increase in systemic steroids, as determined by the investigator.	Up to 4 weeks
Maximum Plasma Concentration of Navarixin (Cmax)	Plasma samples were to be collected at baseline and up to 24 hours after dosing with navarixin at Weeks 1, 2, 3, and 4	Week 1, 2, 3, and 4

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Nair P, Gaga M, Zervas E, Alagha K, Hargreave FE, O'Byrne PM, Stryszak P, Gann L, Sadeh J, Chanez P; Study Investigators. Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils: a randomized, placebo-controlled clinical trial. Clin Exp Allergy. 2012 Jul;42(7):1097-103. doi: 10.1111/j.1365-2222.2012.04014.x.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2008
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: February 29, 2008
• First Submitted That Met QC Criteria: February 29, 2008
• First Posted (Estimate): March 10, 2008

Study Record Updates

• Last Update Posted (Actual): January 2, 2019
• Last Update Submitted That Met QC Criteria: December 10, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: P05365 (Other Identifier: Merck protocol number); 2007-005615-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis