Clinical trial NCT01343407: A Two-part Study of the Effects of MK-1029 in Allergen-Challenged Asthmatics (MK-1029-003)
Official title: A Two-Part, Multicenter, Randomized, Clinical Trial to Study the Effects of Multiple Doses of MK-1029 on the Late Asthmatic Response to Lung Allergen Challenge in Asthmatics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-04-28
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This was a 2-part study in participants with allergen-induced asthma. It included a procedural pilot component (Part 1). Part 1 tested the key procedures and timing of Part 2; no study drug was administered during Part 1. Part 2 included a pre-randomization placebo run-in (Period 1) and 3 treatment periods (Periods 2, 3, and 4) during which participants were randomized to receive double-blind placebo, MK-1029 60 mg or MK-1029 500 mg in a crossover design. The treatment periods were followed by a minimum 21-day washout. Part 2 assessed allergen-induced sputum eosinophils and allergen-induced late asthmatic response (LAR) compared to placebo.


Eligibility criteria: Inclusion Criteria:

Parts 1 and 2

* Is male or a female of non-childbearing potential
* Has a history of allergen-induced asthma for at least 6 months
* Is judged to be in good health (other than asthma)
* Is able to perform reproducible pulmonary function testing
* Has a positive methacholine challenge test on Day -1
* Has an allergic response to house dust mite allergen as defined by positive skin prick test
* Is a nonsmoker and/ or has not used nicotine or nicotine-containing products for at least 12 months
* Has body mass index (BMI) ≥17 kg/m\^2, but ≤33 kg/m\^2

Part 2 only

* Must demonstrate a dual airway response to an allergen challenge in Period 1, decrease in FEV1 of at least 20% 0 to 2 hours after allergen challenge for early asthmatic response (EAR) and a positive late asthmatic response (LAR) to an inhaled allergen challenge as defined by a bronchoconstrictive response of at least 15% reduction in FEV1 3 to 8 hours after allergen challenge
* Can tolerate sputum induction and produce adequate sputum

Exclusion Criteria:

Parts 1 and 2

* Has a history of any illness that, in the opinion of the study investigator, might confound the results of the study or poses additional risk to the participant
* Has recent (4 weeks) or ongoing upper or lower respiratory tract infection
* Is unable to refrain from or anticipates the use of any medication other than the ones permitted in this study
* Has taken oral, intramuscular, intra-articular, high-potency topical or orally inhaled corticosteroids within 8 weeks
* Has taken the following medications outside the washout margins: nasal corticosteroids and anti-leukotrienes within 3 weeks; inhaled long-acting β2-agonists, long-acting antihistamines (e.g., loratadine, sustained-release agents), intra-nasal anticholinergics over-the-counter decongestants within 1 week; short-acting oral decongestants, short-acting antihistamines (e.g., chlorpheniramine) within 48 hours
* Consumes excessive amounts of alcohol or caffeinated beverages
* Has had major surgery, donated or lost 1 unit of blood or participated in another investigational study within 3 months
* Has a history of severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
* Is a nursing mother
* Has a history of receiving anti-immunoglobulin E (IgE) or immunotherapy
* Has a history of serious allergies to drugs or a history of hypersensitivity to mometasone furoate or any of its inactive ingredients such as lactose, or inhaled salbutamol, antihistamines, or any

other potential asthma/anaphylaxis rescue medication

Part 2 only

- Has a decline in FEV1 of 70% or greater from the post allergen diluent baseline and/or FEV1 \<1.0L or has symptomatic drop in FEV1 associated with shortness of breath unresolved with bronchodilators within a reasonable timeframe (60 minutes) after the allergen challenge study in Period 1

Primary outcomes:
measure: Percent Change From Baseline in Percent (%) Eosinophils in Induced Sputum At 8 Hours Post Allergen
timeFrame: Baseline (Day -1) and Day 5 (8 hours after allergen challenge in each treatment period)
measure: Forced Expiratory Volume in One Second (FEV1) From 3 to 8 Hours Postdose (AUC3-8hr) During the Late Asthmatic Response (LAR)
timeFrame: From 3 to 8 hours after allergen challenge on Day 5 of each treatment period
measure: Number of Participants With an Adverse Event (AE)
timeFrame: Up to 26 days in each treatment period
measure: Number of Participants Discontinuing Treatment Due to an AE
timeFrame: Up to 5 days in each treatment period
Secondary outcomes:
measure: Percent Inhibition of the Expression of Cluster of Differentiation (CD)11b on Blood Eosinophils
timeFrame: Baseline (Day -1, predose), 24 hours after allergen challenge on Day 5 in each treatment period
Other outcomes:
measure: Baseline (Pre-Treatment) Percent (%) Eosinophils
timeFrame: Baseline (Day -1), pre-antigen challenge
measure: Baseline Expression of Cluster of Differentiation (CD)11b on Blood Eosinophils
timeFrame: Day 1, predose
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: