Neutrophilic AsthmaPhase 2NCT00632502
Neutrophilic Asthma Study With Navarixin (MK-7123, SCH 527123) (MK-7123-017)(COMPLETED)
A Phase 2 study testing Navarixin and Rescue medication in people with Neutrophilic Asthma, run by Merck Sharp & Dohme LLC.
Trial summary
4-Week Safety Study in Subjects with Neutrophilic Asthma Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Neutrophilic Asthma
- What is being tested?
- Navarixin and Rescue medication
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- No sites listed yet
- Study dates
- 1 May 2008to 1 Feb 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
About this study
Official title: Safety of SCH 527123 in Subjects With Neutrophilic Asthma
4-Week Safety Study in Subjects with Neutrophilic Asthma
Read the detailed description
Effect of treatment with navarixin (MK-7123, SCH 527123) on sputum neutrophils and asthma symptoms
- Conditions
- Neutrophilic Asthma
- Being tested
- Navarixin, Placebo, Rescue medication
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NavarixinDrug
Navarixin 30 mg capsule to be taken by mouth once daily in the morning for 4 weeks.
PlaceboDrug
Placebo capsule to match navarixin to be taken by mouth once daily in the morning for 4 weeks.
Rescue medicationDrug
Participant choice of short-acting beta-2 agonist (salbutamol/albuterol), anticholinergic, or combination medication as needed for asthma symptoms
| Study group | Role | What they receive |
|---|---|---|
| Navarixin | Experimental | Navarixin (MK-7123, SCH 527123) 30 mg capsule, to be taken by mouth once daily in the morning for 4 weeks Receives: Drug: Navarixin; Drug: Rescue medication |
| Placebo | Placebo comparator | Placebo capsule to match navarixin, to be taken by mouth once daily in the morning for 4 weeks Receives: Drug: Placebo; Drug: Rescue medication |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 4 weeks
Secondary outcomes (10)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: Week 1, 2, 3, and 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2008 (estimated)
- Study start1 May 2008
- Primary completion1 Feb 2009
- Study completion1 Feb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neutrophilic AsthmaStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00632502
- Sponsor's protocol ID
- P05365
- Other IDs
- 2007-005615-26, P05365
- Status last verified
- Dec 2018
- First submitted
- 29 Feb 2008
- Last updated
- 2 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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.
PubMed 22702508
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety of SCH 527123 in Subjects With Neutrophilic Asthma
- ClinicalTrials.gov ID
- NCT00632502
- Acronym / sponsor ID
- P05365
- Conditions
- Neutrophilic Asthma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 1 May 2008 (actual)
- Primary completion
- 1 Feb 2009 (actual)
- Study completion
- 1 Feb 2009 (actual)
- First posted
- 10 Mar 2008 (estimated)
- Results
- Posted 18 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
4-Week Safety Study in Subjects with Neutrophilic Asthma
Detailed description
Effect of treatment with navarixin (MK-7123, SCH 527123) on sputum neutrophils and asthma symptoms
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Navarixin | Experimental | Drug: Navarixin, Drug: Rescue medicationNavarixin (MK-7123, SCH 527123) 30 mg capsule, to be taken by mouth once daily in the morning for 4 weeks |
| Placebo | Placebo comparator | Drug: Placebo, Drug: Rescue medicationPlacebo capsule to match navarixin, to be taken by mouth once daily in the morning for 4 weeks |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NavarixinNavarixin 30 mg capsule to be taken by mouth once daily in the morning for 4 weeks. | Drug | Navarixin |
| PlaceboPlacebo capsule to match navarixin to be taken by mouth once daily in the morning for 4 weeks. | Drug | Placebo |
| Rescue medicationParticipant choice of short-acting beta-2 agonist (salbutamol/albuterol), anticholinergic, or combination medication as needed for asthma symptoms | Drug | Navarixin, Placebo |
Primary outcome
Number of Participants Who Maintained an Absolute Peripheral Blood Neutrophil Count >=1500/µL
Time frame: Up to 4 weeks
Peripheral blood neutrophil counts were performed on Day 2 and Weeks 1, 2, 3, and 4 of the treatment period
10 secondary outcomes
Mean Change From Baseline in Sputum Absolute Neutrophil Count
Time frame: Baseline and while on study drug (up to 4 weeks)
Mean Change From Baseline in Total Asthma Symptom Score
Time frame: Baseline and Weeks 1, 2, 3, and 4
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1)
Time frame: Baseline and up to 4 weeks
Change From Baseline in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ[S])
Time frame: Baseline and up to 4 weeks
Number of Participants With an Adverse Event (AE)
Time frame: Up to 5 weeks
Number of Participants With an Electrocardiogram Adverse Event
Time frame: Week 4
Number of Participants With a Laboratory Adverse Event
Time frame: Up to 5 weeks
Number of Participants Who Discontinued the Study Because of an Adverse Event
Time frame: Up to 5 weeks
Number of Participants Who Discontinued Treatment Because of an Adverse Event or a Protocol-defined Clinical Event
Time frame: Up to 4 weeks
Maximum Plasma Concentration of Navarixin (Cmax)
Time frame: Week 1, 2, 3, and 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22702508Nair 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.
- Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Navarixin and Rescue medication in people with Neutrophilic Asthma, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Maintained an Absolute Peripheral Blood Neutrophil Count >=1500/µL (time frame: Up to 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00632502, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jan 2019.