Trial Outcomes & Findings for Early Airway Response to Allergen in Asthmatics (MK-0000-176) (NCT NCT01061333)
NCT ID: NCT01061333
Last Updated: 2015-09-04
Results Overview
Maximal percent drop in FEV1 at 20 minutes post allergen challenge
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
16 participants
Primary outcome timeframe
Pre-allergen challenge and 20 minutes after allergen challenge
Results posted on
2015-09-04
Participant Flow
Participant milestones
| Measure |
Placebo-Montelukast-Nedocromil-Mometasone
Over the course of four 3-day treatment regimens, participants received a single dose of each drug starting with placebo, crossover of nedocromil or montelukast, crossover of nedocromil or montelukast, ending with mometasone; with a 20-day washout between each of the four treatment periods.
|
Placebo-Nedocromil-Montelukast-Mometasone
Over the course of four 3-day treatment regimens, participants received a single dose of each drug starting with placebo, crossover of nedocromil or montelukast, crossover of nedocromil or montelukast, ending with mometasone; with a 20-day washout between each of the four treatment periods.
|
|---|---|---|
|
Period 1: Placebo Run-in
STARTED
|
8
|
8
|
|
Period 1: Placebo Run-in
COMPLETED
|
8
|
8
|
|
Period 1: Placebo Run-in
NOT COMPLETED
|
0
|
0
|
|
Period 2: 20-day Washout
STARTED
|
8
|
8
|
|
Period 2: 20-day Washout
COMPLETED
|
8
|
8
|
|
Period 2: 20-day Washout
NOT COMPLETED
|
0
|
0
|
|
Period 3: Nedocromil-Montelukast X-over
STARTED
|
8
|
8
|
|
Period 3: Nedocromil-Montelukast X-over
COMPLETED
|
8
|
8
|
|
Period 3: Nedocromil-Montelukast X-over
NOT COMPLETED
|
0
|
0
|
|
Period 4: 20-day Washout
STARTED
|
8
|
8
|
|
Period 4: 20-day Washout
COMPLETED
|
8
|
7
|
|
Period 4: 20-day Washout
NOT COMPLETED
|
0
|
1
|
|
Period 5: Nedocromil-Montelukast X-over
STARTED
|
8
|
7
|
|
Period 5: Nedocromil-Montelukast X-over
COMPLETED
|
8
|
7
|
|
Period 5: Nedocromil-Montelukast X-over
NOT COMPLETED
|
0
|
0
|
|
Period 6: 20-day Washout
STARTED
|
8
|
7
|
|
Period 6: 20-day Washout
COMPLETED
|
8
|
7
|
|
Period 6: 20-day Washout
NOT COMPLETED
|
0
|
0
|
|
Period 7: Mometasone
STARTED
|
8
|
7
|
|
Period 7: Mometasone
COMPLETED
|
8
|
7
|
|
Period 7: Mometasone
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Placebo-Montelukast-Nedocromil-Mometasone
Over the course of four 3-day treatment regimens, participants received a single dose of each drug starting with placebo, crossover of nedocromil or montelukast, crossover of nedocromil or montelukast, ending with mometasone; with a 20-day washout between each of the four treatment periods.
|
Placebo-Nedocromil-Montelukast-Mometasone
Over the course of four 3-day treatment regimens, participants received a single dose of each drug starting with placebo, crossover of nedocromil or montelukast, crossover of nedocromil or montelukast, ending with mometasone; with a 20-day washout between each of the four treatment periods.
|
|---|---|---|
|
Period 4: 20-day Washout
Discontinued by Study Team
|
0
|
1
|
Baseline Characteristics
Early Airway Response to Allergen in Asthmatics (MK-0000-176)
Baseline characteristics by cohort
| Measure |
All Participants
n=16 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.
|
|---|---|
|
Age, Continuous
|
31.94 years
STANDARD_DEVIATION 7.47 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-allergen challenge and 20 minutes after allergen challengeMaximal percent drop in FEV1 at 20 minutes post allergen challenge
Outcome measures
| Measure |
Placebo
n=16 Participants
Nedocromil placebo metered dose inhaler, montelukast placebo tablet, mometasone placebo twisthaler
|
Nedocromil
n=16 Participants
Nedocromil 4 mg, administered by metered dose inhaler, 1 hour prior to allergen challenge
|
Montelukast
n=15 Participants
Montelukast 10 mg, administered in a single tablet, 2 hours prior to allergen challenge
|
Mometasone
n=15 Participants
Mometasone furoate 400 mcg, administered by twisthaler, 2 hours prior to allergen challenge
|
|---|---|---|---|---|
|
Change in Forced Expiratory Volume in 1 Second (FEV1)
|
-24.66 Percentage drop in FEV1
Standard Deviation 10.72
|
-8.44 Percentage drop in FEV1
Standard Deviation 6.15
|
-9.15 Percentage drop in FEV1
Standard Deviation 6.96
|
-16.17 Percentage drop in FEV1
Standard Deviation 11.01
|
PRIMARY outcome
Timeframe: Pre-allergen challenge and 5 minutes post allergen challengeFold change over baseline of plasma 9P at 5 minutes post-allergen challenge
Outcome measures
| Measure |
Placebo
n=16 Participants
Nedocromil placebo metered dose inhaler, montelukast placebo tablet, mometasone placebo twisthaler
|
Nedocromil
n=16 Participants
Nedocromil 4 mg, administered by metered dose inhaler, 1 hour prior to allergen challenge
|
Montelukast
n=15 Participants
Montelukast 10 mg, administered in a single tablet, 2 hours prior to allergen challenge
|
Mometasone
n=15 Participants
Mometasone furoate 400 mcg, administered by twisthaler, 2 hours prior to allergen challenge
|
|---|---|---|---|---|
|
Change in Plasma 9α-11β-PGF2 (9P) at 5 Minutes
|
0.77 Fold change over baseline
Standard Deviation 0.21
|
0.97 Fold change over baseline
Standard Deviation 0.17
|
1.08 Fold change over baseline
Standard Deviation 0.44
|
1.00 Fold change over baseline
Standard Deviation 0.35
|
PRIMARY outcome
Timeframe: Pre-allergen challenge and 20 minutes post allergen challengeFold change over baseline of plasma 9P at 20 minutes post-allergen challenge
Outcome measures
| Measure |
Placebo
n=16 Participants
Nedocromil placebo metered dose inhaler, montelukast placebo tablet, mometasone placebo twisthaler
|
Nedocromil
n=16 Participants
Nedocromil 4 mg, administered by metered dose inhaler, 1 hour prior to allergen challenge
|
Montelukast
n=15 Participants
Montelukast 10 mg, administered in a single tablet, 2 hours prior to allergen challenge
|
Mometasone
n=15 Participants
Mometasone furoate 400 mcg, administered by twisthaler, 2 hours prior to allergen challenge
|
|---|---|---|---|---|
|
Change in Plasma 9P at 20 Minutes
|
1.22 Fold change over baseline
Standard Deviation 0.31
|
0.72 Fold change over baseline
Standard Deviation 0.25
|
0.72 Fold change over baseline
Standard Deviation 0.21
|
1.06 Fold change over baseline
Standard Deviation 0.40
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post allergen challengePopulation: Only participants with baseline values were analyzed
Fold change over baseline in Urinary 9P at 2 hours post allergen challenge
Outcome measures
| Measure |
Placebo
n=13 Participants
Nedocromil placebo metered dose inhaler, montelukast placebo tablet, mometasone placebo twisthaler
|
Nedocromil
n=14 Participants
Nedocromil 4 mg, administered by metered dose inhaler, 1 hour prior to allergen challenge
|
Montelukast
n=14 Participants
Montelukast 10 mg, administered in a single tablet, 2 hours prior to allergen challenge
|
Mometasone
n=13 Participants
Mometasone furoate 400 mcg, administered by twisthaler, 2 hours prior to allergen challenge
|
|---|---|---|---|---|
|
Allergen-induced Changes in Urinary 9P
|
1.54 Fold change over baseline
Standard Deviation 2.43
|
1.39 Fold change over baseline
Standard Deviation 2.54
|
1.45 Fold change over baseline
Standard Deviation 4.22
|
1.40 Fold change over baseline
Standard Deviation 2.24
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post allergen challengePopulation: Only participants with baseline values were analyzed
Fold change over baseline in urinary LTE4 at 2 hours post-allergen challenge
Outcome measures
| Measure |
Placebo
n=13 Participants
Nedocromil placebo metered dose inhaler, montelukast placebo tablet, mometasone placebo twisthaler
|
Nedocromil
n=14 Participants
Nedocromil 4 mg, administered by metered dose inhaler, 1 hour prior to allergen challenge
|
Montelukast
n=14 Participants
Montelukast 10 mg, administered in a single tablet, 2 hours prior to allergen challenge
|
Mometasone
n=13 Participants
Mometasone furoate 400 mcg, administered by twisthaler, 2 hours prior to allergen challenge
|
|---|---|---|---|---|
|
Allergen-induced Changes in Urinary Leukotriene (LT) E4
|
1.77 Fold change over baseline
Standard Deviation 1.09
|
1.19 Fold change over baseline
Standard Deviation 1.31
|
1.40 Fold change over baseline
Standard Deviation 1.52
|
1.62 Fold change over baseline
Standard Deviation 1.35
|
SECONDARY outcome
Timeframe: 2 hours post allergen challengePopulation: 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.
Concentrations of LTC4 in sputum at 2 hours post-allergen challenge
Outcome measures
| Measure |
Placebo
n=16 Participants
Nedocromil placebo metered dose inhaler, montelukast placebo tablet, mometasone placebo twisthaler
|
Nedocromil
n=16 Participants
Nedocromil 4 mg, administered by metered dose inhaler, 1 hour prior to allergen challenge
|
Montelukast
n=14 Participants
Montelukast 10 mg, administered in a single tablet, 2 hours prior to allergen challenge
|
Mometasone
n=14 Participants
Mometasone furoate 400 mcg, administered by twisthaler, 2 hours prior to allergen challenge
|
|---|---|---|---|---|
|
Allergen-induced Concentrations of Sputum LTC4
|
13.63 pg/mL
Standard Deviation 8.22
|
14.02 pg/mL
Standard Deviation 12.53
|
13.76 pg/mL
Standard Deviation 5.45
|
12.14 pg/mL
Standard Deviation 6.94
|
SECONDARY outcome
Timeframe: 2 hours post allergen challengePopulation: 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.
Concentrations of LTD4 in sputum at 2 hours post-allergen challenge
Outcome measures
| Measure |
Placebo
n=16 Participants
Nedocromil placebo metered dose inhaler, montelukast placebo tablet, mometasone placebo twisthaler
|
Nedocromil
n=16 Participants
Nedocromil 4 mg, administered by metered dose inhaler, 1 hour prior to allergen challenge
|
Montelukast
n=14 Participants
Montelukast 10 mg, administered in a single tablet, 2 hours prior to allergen challenge
|
Mometasone
n=14 Participants
Mometasone furoate 400 mcg, administered by twisthaler, 2 hours prior to allergen challenge
|
|---|---|---|---|---|
|
Allergen-induced Concentrations of Sputum LTD4
|
17.48 pg/mL
Standard Deviation 15.20
|
18.04 pg/mL
Standard Deviation 31.13
|
18.52 pg/mL
Standard Deviation 9.22
|
17.37 pg/mL
Standard Deviation 36.91
|
SECONDARY outcome
Timeframe: 2 hours post allergen challengePopulation: 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.
Concentrations of LTE4 in sputum at 2 hours post-allergen challenge
Outcome measures
| Measure |
Placebo
n=16 Participants
Nedocromil placebo metered dose inhaler, montelukast placebo tablet, mometasone placebo twisthaler
|
Nedocromil
n=16 Participants
Nedocromil 4 mg, administered by metered dose inhaler, 1 hour prior to allergen challenge
|
Montelukast
n=14 Participants
Montelukast 10 mg, administered in a single tablet, 2 hours prior to allergen challenge
|
Mometasone
n=14 Participants
Mometasone furoate 400 mcg, administered by twisthaler, 2 hours prior to allergen challenge
|
|---|---|---|---|---|
|
Allergen-induced Concentrations of Sputum LTE4
|
115.5 pg/mL
Standard Deviation 129.0
|
149.8 pg/mL
Standard Deviation 178.7
|
181.3 pg/mL
Standard Deviation 227.6
|
140.3 pg/mL
Standard Deviation 215.8
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Nedocromil
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Montelukast
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Mometasone
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=16 participants at risk
Nedocromil placebo metered dose inhaler, montelukast placebo tablet, mometasone placebo twisthaler
|
Nedocromil
n=16 participants at risk
Nedocromil 4 mg, administered by metered dose inhaler, 1 hour prior to allergen challenge
|
Montelukast
n=15 participants at risk
Montelukast 10 mg, administered in a single tablet, 2 hours prior to allergen challenge
|
Mometasone
n=15 participants at risk
Mometasone furoate 400 mcg, administered by twisthaler, 2 hours prior to allergen challenge
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/16
|
6.2%
1/16
|
0.00%
0/15
|
0.00%
0/15
|
|
General disorders
Influenza Like Illness
|
6.2%
1/16
|
0.00%
0/16
|
0.00%
0/15
|
0.00%
0/15
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.00%
0/16
|
6.2%
1/16
|
0.00%
0/15
|
0.00%
0/15
|
|
Injury, poisoning and procedural complications
Joint Sprain
|
6.2%
1/16
|
0.00%
0/16
|
0.00%
0/15
|
0.00%
0/15
|
|
Nervous system disorders
Headache
|
12.5%
2/16
|
6.2%
1/16
|
13.3%
2/15
|
0.00%
0/15
|
|
Nervous system disorders
Presyncope
|
0.00%
0/16
|
0.00%
0/16
|
6.7%
1/15
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis Allergic
|
0.00%
0/16
|
6.2%
1/16
|
0.00%
0/15
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
6.2%
1/16
|
12.5%
2/16
|
6.7%
1/15
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.2%
1/16
|
0.00%
0/16
|
0.00%
0/15
|
0.00%
0/15
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee For multicenter studies, subsequent to the multicenter publication, an investigator and colleagues may publish their data independently. Limitations of single site observations should always be described in such a manuscript. The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this study 60 days prior to submission. Any information identified by the SPONSOR as confidential must be deleted prior to submission.
- Publication restrictions are in place
Restriction type: OTHER