A Two-part Study of the Effects of MK-1029 in Allergen-Challenged Asthmatics (MK-1029-003)

• ClinicalTrials.gov Identifier: NCT01343407
• Recruitment Status: Completed
• First Posted: April 28, 2011
• Results First Posted: February 8, 2019
• Last Update Posted: March 1, 2019
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: MK-1029 10 mg; Drug: MK-1029 100 mg; Drug: Placebo for MK-1029 10 mg; Drug: Placebo for MK-1029 100 mg	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: April 19, 2011
• Actual Primary Completion Date: January 9, 2012
• Actual Study Completion Date: January 9, 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: MK-1029 60 mg; Part 2 - Participants will receive 5 days of double-blind, once-daily MK-1029 60 mg followed by a 21-day washout in Period 2, 3, or 4 in a crossover design	Drug: MK-1029 10 mg; Six capsules once daily for 5 days in Period 2, 3, or 4 in a crossover design; Drug: Placebo for MK-1029 10 mg; Six capsules once daily for 5 days in Period 1, and the same in Period 2, 3, or 4 in a crossover design."
Experimental: MK-1029 500 mg; Part 2 - Participants will receive 5 days of double-blind, once-daily MK-1029 60 mg followed by a 21-day washout in Period 2, 3, or 4 in a crossover design	Drug: MK-1029 100 mg; Five capsules once daily for 5 days in Period 2, 3, or 4 in a crossover design; Drug: Placebo for MK-1029 100 mg; Five capsules once daily for 5 days in Period 2, 3, or 4 in a crossover design
Placebo Comparator: Placebo; Part II - Participants will receive 5 days of double-blind, once-daily MK-1029 60 mg followed by a 21-day washout in Period 2, 3, or 4 in a crossover design	Drug: Placebo for MK-1029 10 mg; Six capsules once daily for 5 days in Period 1, and the same in Period 2, 3, or 4 in a crossover design."; Drug: Placebo for MK-1029 100 mg; Five capsules once daily for 5 days in Period 2, 3, or 4 in a crossover design

Outcome Measures

Primary Outcome Measures :

1. Percent Change From Baseline in Percent (%) Eosinophils in Induced Sputum At 8 Hours Post Allergen [ Time Frame: Baseline (Day -1) and Day 5 (8 hours after allergen challenge in each treatment period) ]
   The effect of MK-1029 on the reduction of percent (%) sputum eosinophils following allergen challenge with standardized cat pelt or hair (CPH) allergen extract was assessed. Baseline % eosinophils were measured before treatment (and pre-allergen challenge) on Day -1. The change from baseline in allergen-induced % sputum eosinophils at 8 hr post allergen challenge testing on Day 5 was analyzed using a repeated measures linear mixed effects model with treatment, period, time, time-by-treatment interaction as fixed factors, and participant as a random factor. Outcome Measure 6 shows % eosinophil values at baseline.
2. Forced Expiratory Volume in One Second (FEV1) From 3 to 8 Hours Postdose (AUC3-8hr) During the Late Asthmatic Response (LAR) [ Time Frame: From 3 to 8 hours after allergen challenge on Day 5 of each treatment period ]
   The effect of MK-1029 on the FEV1 AUC(3-8hr) during LAR was assessed. The unit of measure for an FEV1 AUC value is L*hr. The effect of treatment on LAR was assessed as the percent-fall in FEV1 AUC(3-8hr), evaluated by spirometry following allergen challenge on Day 5. The FEV1 AUC(3-8hr) during LAR was analyzed using a linear mixed effects model with treatment and period as fixed factors and participant as a random factor.
3. Number of Participants With an Adverse Event (AE) [ Time Frame: Up to 26 days in each treatment period ]
   The number of participants who had at least one adverse event (AE) during study treatment and follow-up was assessed. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product.
4. Number of Participants Discontinuing Treatment Due to an AE [ Time Frame: Up to 5 days in each treatment period ]
   The number of participants who discontinued study treatment due to an AE was assessed. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product.

Secondary Outcome Measures :

1. Percent Inhibition of the Expression of Cluster of Differentiation (CD)11b on Blood Eosinophils [ Time Frame: Baseline (Day -1, predose), 24 hours after allergen challenge on Day 5 in each treatment period ]
   The concentration of CD11b in whole blood samples was assessed. The percent-inhibition of CD11b (a cell-surface biomarker on activated eosinophils) was assessed following inhaled allergen challenge on Day 5. Inhibition of CD11b expression was assessed by analyzing the % inhibition of CD11b expression from baseline (Day -1) using a linear mixed-effects model with period, treatment, time, and treatment by time as fixed terms and subject as a random term. Outcome Measure 7 shows CD11b expression values at baseline.

Other Outcome Measures:

1. Baseline (Pre-Treatment) Percent (%) Eosinophils [ Time Frame: Baseline (Day -1), pre-antigen challenge ]
   Baseline values of the percent (%) sputum eosinophils were measured pre-antigen challenge on Day -1. The baseline % eosinophil values were provided to assess the change from baseline after treatment.
2. Baseline Expression of Cluster of Differentiation (CD)11b on Blood Eosinophils [ Time Frame: Day 1, predose ]
   Baseline values for the antibody-specific expression of CD11b in whole blood samples, as obtained by flow cytometry, were obtained. The baseline CD11b values were obtained before treatment with MK-1029 60 mg, MK-1029 500 mg, or placebo, and were used to assess the effects of treatment.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

More Information

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT01343407
• Other Study ID Numbers: 1029-003; 2010-022391-31 ( EudraCT Number ); MK-1029-003 ( Other Identifier: Merck Protocol Number )
• First Posted: April 28, 2011
• Results First Posted: February 8, 2019
• Last Update Posted: March 1, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases