Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Efficacy and Safety of Navarixin (SCH 527123) in Participants With Allergen-Induced Asthma (P05363)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00688467
First received: May 29, 2008
Last updated: September 26, 2014
Last verified: September 2014

May 29, 2008
September 26, 2014
June 2008
March 2009   (final data collection date for primary outcome measure)
Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 3 to 7 Hours (AUC3-7hr) After Allergen Challenge Following 9 Days Pretreatment With Navarixin [ Time Frame: Baseline and between 3 and 7 hours after allergen challenge ] [ Designated as safety issue: No ]
This is a measure of the Late Asthmatic Response (LAR) between 3 and 7 hours after allergen challenge. Allergen challenge was administered 1 hour after the ninth daily dose of study drug in each treatment period. Baseline FEV1 was defined as the prechallenge FEV1 in the treatment period. A percent change >0 indicates a fall in FEV1 after allergen challenge. The reported standard deviations (SDs) are pooled across all treatment groups. The rationale for the use of an analysis of variance using pooled SD values is the assumption that the SDs are similar across treatment groups. The pooled SD values were used in the calculation of test statistics to assess treatment differences (p-value generation).
LAR area under the curve from 3 to 7 hours (AUC(3-7 hr)) expressed as % change in FEV1 from the prechallenge value of FEV1 taken from 3 to 7 hours postallergen challenge, following 9 days pretreatment with SCH 527123. [ Time Frame: Visits 9 and 14 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00688467 on ClinicalTrials.gov Archive Site
  • Maximum Change From Baseline in FEV1 During the LAR Following 9 Days of Pretreatment With Navarixin [ Time Frame: Baseline and between 3 and 7 hours after allergen challenge ] [ Designated as safety issue: No ]
    Allergen challenge was administered 1 hour after the ninth daily dose of study drug in each treatment period. Baseline FEV1 was defined as the prechallenge FEV1 in the treatment period. The LAR was 3 to 7 hours after allergen challenge. The reported SDs are pooled across all treatment groups. The rationale for the use of an analysis of variance using pooled SD values is the assumption that the SDs are similar across treatment groups. The pooled SD values were used in the calculation of test statistics to assess treatment differences (p-value generation).
  • Change in Concentration of Methacholine That Initiated a 20% Reduction in FEV1 From 24 Hours Before (Baseline) to 24 Hours After Allergen Challenge [ Time Frame: Baseline and 24 hours after allergen challenge ] [ Designated as safety issue: No ]
    This is a measure of allergen-induced changes in airway responsiveness to methacholine. The reported SDs are pooled across all treatment groups. The rationale for the use of an analysis of variance using pooled SD values is the assumption that the SDs are similar across treatment groups.
  • Percent Change From Baseline in FEV1 Area Under the Curve From 0 to 2 Hours (AUC0-2hr) After Allergen Challenge Following 9 Days Pretreatment With Navarixin [ Time Frame: Baseline and between 0 to 2 hours after allergen challenge ] [ Designated as safety issue: No ]
    This is a measure of Early Asthmatic Response (EAR) between 0 to 2 hours after allergen challenge. Allergen challenge was administered 1 hour after the ninth daily dose of study drug in each treatment period. A percent change >0 indicates a reduction in FEV1 from before to after allergen challenge. The reported SDs are pooled across all treatment groups. The rationale for the use of an analysis of variance using pooled SD values is the assumption that the SDs are similar across treatment groups. The pooled SD values were used in the calculation of test statistics to assess treatment differences (p-value generation).
  • Maximum Percent Change From Baseline in FEV1 During the Early Asthmatic Response Following 9 Days of Pretreatment With Navarixin [ Time Frame: Baseline and between 0 to 2 hours after allergen challenge ] [ Designated as safety issue: No ]
    Allergen challenge was administered 1 hour after the ninth daily dose of study drug in each treatment period. The EAR was 0 to 2 hours after allergen challenge. The reported SDs are pooled across all treatment groups. The rationale for the use of an analysis of variance using pooled SD values is the assumption that the SDs are similar across treatment groups. The pooled SD values were used in the calculation of test statistics to assess treatment differences (p-value generation).
  • Change From Baseline in Sputum Neutrophils After Allergen Challenge Following 9 Days Pretreatment With Navarixin [ Time Frame: Baseline and 7 and 24 hours after allergen challenge ] [ Designated as safety issue: No ]
    Induced sputum samples were collected via the nebulized method. Baseline values were determined at 24 hours before allergen challenge in each treatment period. Sputum neutrophils were measured as percent of total white blood cells. The reported SDs are pooled across all treatment groups. The rationale for the use of an analysis of variance using pooled SD values is the assumption that the SDs are similar across treatment groups.
  • Change From Baseline in Peripheral Blood Eosinophil Count After Allergen Challenge Following 9 Days Pretreatment With Navarixin [ Time Frame: Baseline and 7 and 24 hours after allergen challenge ] [ Designated as safety issue: No ]
    Baseline values were determined at 24 hours before allergen challenge in each treatment period. The reported SDs are pooled across all treatment groups. The rationale for the use of an analysis of variance using pooled SD values is the assumption that the SDs are similar across treatment groups.
  • Change From Baseline in Sputum Interleukin 8 (IL-8) After Allergen Challenge Following 9 Days Pretreatment With Navarixin [ Time Frame: Baseline and 7 and 24 hours after allergen challenge ] [ Designated as safety issue: No ]
    Induced sputum samples were to be collected via the nebulized method. IL-8 level was measured in the sputum supernatant. Baseline values were determined at 24 hours before allergen challenge in each treatment period. The reported SDs are pooled across all treatment groups. The rationale for the use of an analysis of variance using pooled SD values is the assumption that the SDs are similar across treatment groups.
  • Change From Baseline in Sputum Neutrophil Elastase After Allergen Challenge Following 9 Days Pretreatment With Navarixin [ Time Frame: Baseline and 7 and 24 hours after allergen challenge ] [ Designated as safety issue: No ]
    Induced sputum samples were to be collected via the nebulized method. Neutrophil elastase activity was measured in the sputum supernatant as milli units/mL (mU/mL). Baseline values were determined at 24 hours before allergen challenge in each treatment period. The reported SDs are pooled across all treatment groups. The rationale for the use of an analysis of variance using pooled SD values is the assumption that the SDs are similar across treatment groups.
  • Change From Baseline in Sputum Myeloperoxidase (MPO) Level After Allergen Challenge Following 9 Days Pretreatment With Navarixin [ Time Frame: Baseline and 7 and 24 hours after allergen challenge ] [ Designated as safety issue: No ]
    Induced sputum samples were to be collected via the nebulized method. MPO level was measured in the sputum supernatant.
  • Change From Baseline in Sputum Eosinophil Cationic Protein (ECP) Level After Allergen Challenge Following 9 Days Pretreatment With Navarixin [ Time Frame: Baseline and 7 and 24 hours after allergen challenge ] [ Designated as safety issue: No ]
    Induced sputum samples were to be collected via the nebulized method. ECP level was measured in the sputum supernatant.
  • Number of Participants With an Adverse Event (AE) [ Time Frame: Up to 48 days ] [ Designated as safety issue: Yes ]
    An AE is any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to study drug. AEs were reported based on the study drug taken at the time of the event.
  • Number of Participants Discontinued From the Study Because of an Adverse Event [ Time Frame: Up to 48 days ] [ Designated as safety issue: Yes ]
    An AE is any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to study drug. Discontinuations due to an AE are reported based on the study drug taken at the time of the event.
  • Maximum percent fall in FEV1 during the late response following 9 days of pretreatment with SCH 527123. [ Time Frame: Visits 9 and 14 ] [ Designated as safety issue: Yes ]
  • LAR AUC(3-7 hr), expressed as actual change in FEV1 from preallergen FEV1 taken from 3 to 7 hours postallergen challenge, following 9 days of pretreatment with SCH 527123. [ Time Frame: Visits 9 and 14 ] [ Designated as safety issue: Yes ]
  • Changes in airway responsiveness as measured by methacholine PC20 24 hours postallergen challenge. [ Time Frame: Visits 9 and 14 ] [ Designated as safety issue: Yes ]
  • Reduction in sputum neutrophils and eosinophils at 7 and 24 hours postallergen challenge. [ Time Frame: Visits 9 and 14 ] [ Designated as safety issue: Yes ]
  • Attenuation of EAR (maximum percent fall in FEV1 from preallergen FEV1 0-2 hours postchallenge) and EAR UC(0-2 hr) following 9 days of pretreatment with SCH 527123. [ Time Frame: Visits 9 and 14 ] [ Designated as safety issue: Yes ]
  • Changes in interleukin 8 (IL-8), myeloperoxidase (MPO), neutrophil elastase, and eosinophil cationic protein (ECP) levels in sputum at 7 and 24 hours postallergen challenge. [ Time Frame: Visits 9 and 14 ] [ Designated as safety issue: Yes ]
  • Safety and tolerability as measured by peripheral neutrophil counts, asthma symptoms, frequency of use of rescue medication, PFTs, ECGs, labs, and AEs. [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Efficacy and Safety of Navarixin (SCH 527123) in Participants With Allergen-Induced Asthma (P05363)
A Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Efficacy and Safety of SCH 527123 in Subjects With Allergen-Induced Asthma

Evaluation of treatment in participants with mild asthma.

To evaluate the effect of navarixin (MK-527123, SCH 527123) treatment on allergen-induced late asthmatic response (LAR) in participants with mild asthma.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Asthma
  • Drug: Navarixin
    30 mg capsule to be taken once daily in the morning for 10 days during Treatment Period 1 or Treatment Period 2
    Other Name: SCH 527123
  • Drug: Placebo
    Matching capsule to be taken once daily in the morning for 10 days during Treatment Period 1 or Treatment Period 2
  • Experimental: Navarixin → Placebo
    Navarixin 30 mg capsule to be taken once daily in the morning for 10 days in Treatment Period 1, followed by a 2-4 week washout period, followed by matching placebo capsule to be taken once daily in the morning for 10 days in Treatment Period 2
    Interventions:
    • Drug: Navarixin
    • Drug: Placebo
  • Experimental: Placebo → Navarixin
    Matching placebo capsule to be taken once daily in the morning for 10 days in Treatment Period 1, followed by a 2-4 week washout period, followed by navarixin 30 mg capsule to be taken once daily in the morning for 10 days in Treatment Period 2
    Interventions:
    • Drug: Navarixin
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
19
March 2009
March 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Man or woman 18 to 65 years of age of any race.
  • Has mild, stable, allergic asthma as defined by American Thoracic Society criteria.
  • Has history of episodic wheezing and shortness of breath.
  • Has Forced Expiratory Volume in 1 second (FEV1) of at least 70% of predicted at Screening and within 10% of preallergen screening value at both baselines.
  • Has positive methacholine challenge at Screening. Methacholine challenges are considered positive if decreases of at least 20% in the FEV1 occur at a concentration of less than or equal to 16 mg/mL.
  • Baseline methacholine PC20 (concentration that initiated a 20% fall in FEV1) must be within 1 doubling concentration of the preallergen screening PC20 to enter treatment.
  • Has positive skin-prick test to common allergens (cat, dust mite, grass, pollen).
  • Has a positive Early Asthmatic Response of >=20% fall in FEV1 measured from the FEV1 immediately prior to challenge, and Late Asthmatic Response of >=15% fall in FEV1 from the FEV1 measured immediately prior to challenge during Screening period.
  • Has been free from asthma exacerbation for at least 4 weeks before Screening. An exacerbation is defined as an occurrence of any clinical deterioration of asthma that requires emergency treatment, hospitalization due to asthma, or treatment with additional medication, as judged by the clinical investigator.
  • Has been free from relevant seasonal allergen exposure for at least 4 weeks before the study and be able to remain so for the duration of the study.
  • Has a current nonsmoking status. If previous smokers, cumulative smoking history must be fewer than 10 pack-years (pack-year=20 cigarettes smoked daily for 1 year). Previous smokers must not have smoked within 1 year before Screening.
  • Is willing to give written informed consent to participate in the study.
  • Has the ability to comply with the dosing regimen, to adhere to the visit schedule, and to participate in all treatment procedures, including sputum induction.
  • Female participant of childbearing potential must have a negative serum pregnancy tests (human chorionic gonadotropin; hCG) at Screening and must use 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 agrees to continue using it while in the study (Screening and Treatment Periods). Medically acceptable, highly effective forms of birth control include hormonal implants, oral contraceptives, hormonal patches, intravaginal ring, medically acceptable prescribed intrauterine devices (IUDs), and a monogamous relationship with a male partner who has had a vasectomy. A female participant 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 participant should be encouraged to continue using a highly effective method of birth control for 30 days following the end of treatment.
  • Participants, if male and sexually active with women of childbearing potential, must agree to use an adequate form of contraception for the duration of the study and to have sexual relations with only those women who use a highly effective birth control method.
  • Clinical laboratory tests (complete blood count [CBC], blood chemistries, and urinalysis) must be within normal limits or clinically acceptable to the investigator/sponsor.

Exclusion Criteria:

  • Has had a diagnosis of chronic obstructive pulmonary disease (COPD) or any other clinically relevant lung disease (eg, cystic fibrosis, pulmonary fibrosis, bronchiectasis) other than mild allergic asthma, or has a history of having been intubated.
  • Has had a worsening of a respiratory tract infection within 4 weeks before Screening.
  • Has had any clinically significant abnormality; history of clinically significant hypotensive episodes of fainting, dizziness, or lightheadedness; history or symptoms of cardiovascular disease; significant neurologic disease; or hematologic abnormality, including coagulopathy; or has a medication regimen or clinically relevant medical condition other than asthma that may interfere with the effect of study medication.
  • Had a peripheral blood neutrophil (PBN) count of <3 × 10^9/L at the Screening Visit.
  • Has an allergy/sensitivity to the study drug or its excipients.
  • Is pregnant, breast-feeding, or intends to become pregnant during the study.
  • Has used any investigational drug within 30 days or 5 half-lives of Screening.
  • Is presently participating in any other clinical study.
  • Is part of the staff personnel directly involved with this study
  • Is a family member of the investigational study staff.
  • Has received any treatment prohibited by the protocol (Table 3), or any medication that may interfere with the effect of the study medication more recently than the indicated washout period prior to Screening, or must continue to receive the prohibited treatment.
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00688467
P05363, MK-7123-016
No
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Study Director: Medical Director Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP