Asthma
Conditions
Brief summary
This study will assess the Early Airway Response (EAR) associated change in forced expiratory volume in one second (FEV1) and plasma 9α-11ß-PGF2 ('9P') after single dose pretreatment of nedocromil, montelukast, and mometasone.
Interventions
DRUGNedocromil
Nedocromil 4 mg, as metered dose inhaler 1 hour prior to allergen challenge
Montelukast single 10 mg tablet administered 2 hours prior to allergen challenge
Mometasone furoate 400 mcg by twisthaler, administered 2 hours prior to allergen challenge
DRUGPlacebo
Mometasone placebo twisthaler, Nedocromil placebo metered dose inhaler, Montelukast placebo tablet
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* History of mild to moderate Asthma * In good general health (except for asthma) * Stable and free of respiratory infection * Nonsmoker * Females highly unlikely to conceive (surgically sterilized, postmenopausal, or agrees to use 2 acceptable methods of birth control)
Exclusion criteria
* Nursing mother * Recent or ongoing upper or lower respiratory tract infection * Unable to refrain from or anticipates the use of any prescription and non-prescription drugs * Consumes excessive amounts of alcohol or caffeine * History of stroke, chronic seizures, or major neurological disorder * History of cancer * Received a vaccination within the past 3 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Forced Expiratory Volume in 1 Second (FEV1) | Pre-allergen challenge and 20 minutes after allergen challenge | Maximal percent drop in FEV1 at 20 minutes post allergen challenge |
| Change in Plasma 9α-11β-PGF2 (9P) at 5 Minutes | Pre-allergen challenge and 5 minutes post allergen challenge | Fold change over baseline of plasma 9P at 5 minutes post-allergen challenge |
| Change in Plasma 9P at 20 Minutes | Pre-allergen challenge and 20 minutes post allergen challenge | Fold change over baseline of plasma 9P at 20 minutes post-allergen challenge |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Allergen-induced Concentrations of Sputum LTD4 | 2 hours post allergen challenge | Concentrations of LTD4 in sputum at 2 hours post-allergen challenge |
| Allergen-induced Changes in Urinary 9P | Baseline and 2 hours post allergen challenge | Fold change over baseline in Urinary 9P at 2 hours post allergen challenge |
| Allergen-induced Concentrations of Sputum LTE4 | 2 hours post allergen challenge | Concentrations of LTE4 in sputum at 2 hours post-allergen challenge |
| Allergen-induced Changes in Urinary Leukotriene (LT) E4 | Baseline and 2 hours post allergen challenge | Fold change over baseline in urinary LTE4 at 2 hours post-allergen challenge |
| Allergen-induced Concentrations of Sputum LTC4 | 2 hours post allergen challenge | Concentrations of LTC4 in sputum at 2 hours post-allergen challenge |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Over the course of four 3-day treatment regimens, participants received a single dose of each drug starting with placebo, nedocromil or montelukast, nedocromil or montelukast, ending with mometasone; with a 20-day washout between each of the four treatment periods. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 4: 20-day Washout | Discontinued by Study Team | 0 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 31.94 years STANDARD_DEVIATION 7.47 |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 16 | 4 / 16 | 3 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Change in Forced Expiratory Volume in 1 Second (FEV1)
Maximal percent drop in FEV1 at 20 minutes post allergen challenge
Time frame: Pre-allergen challenge and 20 minutes after allergen challenge
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Forced Expiratory Volume in 1 Second (FEV1) | -24.66 Percentage drop in FEV1 | Standard Deviation 10.72 |
| Nedocromil | Change in Forced Expiratory Volume in 1 Second (FEV1) | -8.44 Percentage drop in FEV1 | Standard Deviation 6.15 |
| Montelukast | Change in Forced Expiratory Volume in 1 Second (FEV1) | -9.15 Percentage drop in FEV1 | Standard Deviation 6.96 |
| Mometasone | Change in Forced Expiratory Volume in 1 Second (FEV1) | -16.17 Percentage drop in FEV1 | Standard Deviation 11.01 |
p-value: <0.000190% CI: [10.74, 21.69]ANCOVA
p-value: 0.000190% CI: [10, 21.02]ANCOVA
p-value: 0.043290% CI: [1.78, 15.2]ANCOVA
Primary
Change in Plasma 9P at 20 Minutes
Fold change over baseline of plasma 9P at 20 minutes post-allergen challenge
Time frame: Pre-allergen challenge and 20 minutes post allergen challenge
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Plasma 9P at 20 Minutes | 1.22 Fold change over baseline | Standard Deviation 0.31 |
| Nedocromil | Change in Plasma 9P at 20 Minutes | 0.72 Fold change over baseline | Standard Deviation 0.25 |
| Montelukast | Change in Plasma 9P at 20 Minutes | 0.72 Fold change over baseline | Standard Deviation 0.21 |
| Mometasone | Change in Plasma 9P at 20 Minutes | 1.06 Fold change over baseline | Standard Deviation 0.4 |
p-value: <0.000190% CI: [0.5, 0.7]ANCOVA
p-value: <0.000190% CI: [0.49, 0.7]ANCOVA
p-value: 0.267990% CI: [0.69, 1.08]ANCOVA
Primary
Change in Plasma 9α-11β-PGF2 (9P) at 5 Minutes
Fold change over baseline of plasma 9P at 5 minutes post-allergen challenge
Time frame: Pre-allergen challenge and 5 minutes post allergen challenge
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Plasma 9α-11β-PGF2 (9P) at 5 Minutes | 0.77 Fold change over baseline | Standard Deviation 0.21 |
| Nedocromil | Change in Plasma 9α-11β-PGF2 (9P) at 5 Minutes | 0.97 Fold change over baseline | Standard Deviation 0.17 |
| Montelukast | Change in Plasma 9α-11β-PGF2 (9P) at 5 Minutes | 1.08 Fold change over baseline | Standard Deviation 0.44 |
| Mometasone | Change in Plasma 9α-11β-PGF2 (9P) at 5 Minutes | 1.00 Fold change over baseline | Standard Deviation 0.35 |
p-value: 0.04390% CI: [1.05, 1.54]ANCOVA
p-value: 0.0190% CI: [1.15, 1.72]ANCOVA
p-value: 0.08690% CI: [1.01, 1.67]ANCOVA
Secondary
Allergen-induced Changes in Urinary 9P
Fold change over baseline in Urinary 9P at 2 hours post allergen challenge
Time frame: Baseline and 2 hours post allergen challenge
Population: Only participants with baseline values were analyzed
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Allergen-induced Changes in Urinary 9P | 1.54 Fold change over baseline | Standard Deviation 2.43 |
| Nedocromil | Allergen-induced Changes in Urinary 9P | 1.39 Fold change over baseline | Standard Deviation 2.54 |
| Montelukast | Allergen-induced Changes in Urinary 9P | 1.45 Fold change over baseline | Standard Deviation 4.22 |
| Mometasone | Allergen-induced Changes in Urinary 9P | 1.40 Fold change over baseline | Standard Deviation 2.24 |
p-value: 0.762290% CI: [0.51, 1.59]ANCOVA
p-value: 0.846890% CI: [0.53, 1.65]ANCOVA
p-value: 0.61490% CI: [0.65, 1.26]ANCOVA
Secondary
Allergen-induced Changes in Urinary Leukotriene (LT) E4
Fold change over baseline in urinary LTE4 at 2 hours post-allergen challenge
Time frame: Baseline and 2 hours post allergen challenge
Population: Only participants with baseline values were analyzed
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Allergen-induced Changes in Urinary Leukotriene (LT) E4 | 1.77 Fold change over baseline | Standard Deviation 1.09 |
| Nedocromil | Allergen-induced Changes in Urinary Leukotriene (LT) E4 | 1.19 Fold change over baseline | Standard Deviation 1.31 |
| Montelukast | Allergen-induced Changes in Urinary Leukotriene (LT) E4 | 1.40 Fold change over baseline | Standard Deviation 1.52 |
| Mometasone | Allergen-induced Changes in Urinary Leukotriene (LT) E4 | 1.62 Fold change over baseline | Standard Deviation 1.35 |
p-value: 0.000690% CI: [0.57, 0.8]ANCOVA
p-value: 0.029190% CI: [0.67, 0.94]ANCOVA
p-value: 0.373890% CI: [0.77, 1.08]ANCOVA
Secondary
Allergen-induced Concentrations of Sputum LTC4
Concentrations of LTC4 in sputum at 2 hours post-allergen challenge
Time frame: 2 hours post allergen challenge
Population: Pre-imputation status. Missing data points were excluded and values below the lower limit of quantification (LLOQ) were included in the analysis with an assigned value of assay LLOQ.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Allergen-induced Concentrations of Sputum LTC4 | 13.63 pg/mL | Standard Deviation 8.22 |
| Nedocromil | Allergen-induced Concentrations of Sputum LTC4 | 14.02 pg/mL | Standard Deviation 12.53 |
| Montelukast | Allergen-induced Concentrations of Sputum LTC4 | 13.76 pg/mL | Standard Deviation 5.45 |
| Mometasone | Allergen-induced Concentrations of Sputum LTC4 | 12.14 pg/mL | Standard Deviation 6.94 |
p-value: 0.750190% CI: [0.88, 1.2]ANOVA
p-value: 0.94190% CI: [0.81, 1.25]ANOVA
p-value: 0.116590% CI: [0.79, 1.01]ANOVA
Secondary
Allergen-induced Concentrations of Sputum LTD4
Concentrations of LTD4 in sputum at 2 hours post-allergen challenge
Time frame: 2 hours post allergen challenge
Population: Pre-imputation status. Missing data points were excluded and values below the lower limit of quantification (LLOQ) were included in the analysis with an assigned value of assay LLOQ.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Allergen-induced Concentrations of Sputum LTD4 | 17.48 pg/mL | Standard Deviation 15.2 |
| Nedocromil | Allergen-induced Concentrations of Sputum LTD4 | 18.04 pg/mL | Standard Deviation 31.13 |
| Montelukast | Allergen-induced Concentrations of Sputum LTD4 | 18.52 pg/mL | Standard Deviation 9.22 |
| Mometasone | Allergen-induced Concentrations of Sputum LTD4 | 17.37 pg/mL | Standard Deviation 36.91 |
p-value: 0.861690% CI: [0.76, 1.41]ANOVA
p-value: 0.751290% CI: [0.77, 1.45]ANOVA
p-value: 0.972390% CI: [0.72, 1.37]ANOVA
Secondary
Allergen-induced Concentrations of Sputum LTE4
Concentrations of LTE4 in sputum at 2 hours post-allergen challenge
Time frame: 2 hours post allergen challenge
Population: Pre-imputation status. Missing data points were excluded and values below the lower limit of quantification (LLOQ) were included in the analysis with an assigned value of assay LLOQ.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Allergen-induced Concentrations of Sputum LTE4 | 115.5 pg/mL | Standard Deviation 129 |
| Nedocromil | Allergen-induced Concentrations of Sputum LTE4 | 149.8 pg/mL | Standard Deviation 178.7 |
| Montelukast | Allergen-induced Concentrations of Sputum LTE4 | 181.3 pg/mL | Standard Deviation 227.6 |
| Mometasone | Allergen-induced Concentrations of Sputum LTE4 | 140.3 pg/mL | Standard Deviation 215.8 |
p-value: 0.198390% CI: [0.92, 1.82]ANOVA
p-value: 0.087290% CI: [1.02, 2.42]ANOVA
p-value: 0.249990% CI: [0.91, 1.62]ANOVA