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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00632502
First received: February 29, 2008
Last updated: November 14, 2014
Last verified: November 2014
  Purpose

4-Week Safety Study in Subjects with Neutrophilic Asthma


Condition Intervention Phase
Neutrophilic Asthma
Drug: Navarixin
Drug: Placebo
Drug: Rescue medication
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Safety of SCH 527123 in Subjects With Neutrophilic Asthma

Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of Participants Who Maintained an Absolute Peripheral Blood Neutrophil Count >=1500/µL [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: Yes ]
    Peripheral blood neutrophil counts were performed on Day 2 and Weeks 1, 2, 3, and 4 of the treatment period


Secondary Outcome Measures:
  • Mean Change From Baseline in Sputum Absolute Neutrophil Count [ Time Frame: Baseline and while on study drug (up to 4 weeks) ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in Total Asthma Symptom Score [ Time Frame: Baseline and Weeks 1, 2, 3, and 4 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1) [ Time Frame: Baseline and up to 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ[S]) [ Time Frame: Baseline and up to 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With an Adverse Event (AE) [ Time Frame: Up to 5 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With an Electrocardiogram Adverse Event [ Time Frame: Week 4 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With a Laboratory Adverse Event [ Time Frame: Up to 5 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants Who Discontinued the Study Because of an Adverse Event [ Time Frame: Up to 5 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants Who Discontinued Treatment Because of an Adverse Event or a Protocol-defined Clinical Event [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Maximum Plasma Concentration of Navarixin (Cmax) [ Time Frame: Week 1, 2, 3, and 4 ] [ Designated as safety issue: No ]
    Plasma samples were to be collected at baseline and up to 24 hours after dosing with navarixin at Weeks 1, 2, 3, and 4


Enrollment: 37
Study Start Date: May 2008
Study Completion Date: February 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: 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

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00632502

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00632502     History of Changes
Other Study ID Numbers: P05365, 2007-005615-26, P05365
Study First Received: February 29, 2008
Results First Received: October 14, 2014
Last Updated: November 14, 2014
Health Authority: Greece: National Drug Authority

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Lung Diseases
Lung Diseases, Obstructive
Respiratory Hypersensitivity
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on November 20, 2014