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Pemirolast in Allergen Challenge (PEMAG) (PEMAG)

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ClinicalTrials.gov Identifier: NCT03119714
Recruitment Status : Unknown
Verified April 2017 by Barbro Dahlen, Karolinska University Hospital.
Recruitment status was:  Recruiting
First Posted : April 19, 2017
Last Update Posted : April 19, 2017
Sponsor:
Collaborators:
Experimental Asthma and Allergy Research Unit, Karolinska Institutet
Unit for Chemistry II, Department of Medical Biochemistry, Karolinska Institutet
Occupational and Environmental Medicine, Sahlgrenska UH, Gothenburg
Div Clinical Pharmacology, Karolinska University Hospital
Dept. Respiratory Medicine, University of Amsterdam, Amsterdam
The Centre for Infection Medicine, Karolinska Institutet
Information provided by (Responsible Party):
Barbro Dahlen, Karolinska University Hospital

Brief Summary:
The purpose of this study is to establish the influence of the non-steroidal candidate-drug pemirolast on allergen-induced airway obstruction and inflammation in allergic subjects with asthma. Pemirolast is an orally available inhibitor of the release of mast cell mediators. The study will therefore test the hypothesis that global inhibition of the mast cell, resulting in decreased production of most of its mediator molecules, will provide a highly significant anti-asthmatic effect.

Condition or disease Intervention/treatment Phase
Allergic Asthma Drug: Pemirolast Drug: Placebo Oral Tablet Phase 2

Detailed Description:
This is a crossover randomized double blind, placebo-controlled study where the early and late response to allergen inhalation challenge will be compared during two treatment periods, with pemirolast 200 mg bid for 14 (to 16) days and matching placebo, respectively. Non-smoking female and male subjects (n = 12-15) with intermittent atopic asthma, requiring only β2-agonists to treat their asthma, will be recruited. A total of twelve subjects who demonstrate an early and a late asthmatic response to inhaled allergen challenge are required to complete the study for the primary end-point. The sample size is sufficient according to experience from a large number of studies and published power calculations of the model. The effects of pemirolast have never been studied before in an allergen provocation model. Primary variable is the effect of treatment on the mean maximum fall in forced expiratory volume in one second (FEV1) during the early and the late asthmatic reactions induced by allergen. Secondary variables are the effect on mast cell activation and airway inflammation measured as the urinary excretion of metabolites of prostaglandins and other lipid mediators and the percentage of sputum eosinophils, respectively. Tertiary variables are the effect of treatment on airway responsiveness expressed as the provocative dose of methacholine causing 20 per cent decrease in FEV1 (PD20FEV1), as well as biomarkers of airway inflammation in saliva, sputum, exhaled air and blood.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Placebo-controlled, Cross-over, Study to Assess the Efficacy of the Oral Mast Cell Inhibitor Pemirolast in Allergen-induced Airway Obstruction and Inflammation in Subjects With Allergic Asthma
Study Start Date : November 2016
Estimated Primary Completion Date : February 2018
Estimated Study Completion Date : April 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma Choking

Arm Intervention/treatment
Active Comparator: Pemirolast
Pemirolast 200mg bid 14-16 days
Drug: Pemirolast
Treatment with pemirolast 200 mg bid for 14-16 days
Other Name: CRD 007

Placebo Comparator: Placebo Oral Tablet
Matching placebo bid 14-16 days
Drug: Placebo Oral Tablet
Treatment with placebo bid for 14-16 days




Primary Outcome Measures :
  1. Bronchoconstriction measured as fall in FEV1 during the early (EAR) and late (LAR) asthmatic reaction induced by allergen [ Time Frame: After treatment with pemirolast or matching placebo for 14-16 days ]

Secondary Outcome Measures :
  1. Mast cell activation measured as urinary excretion of metabolites of lipid mediators (prostaglandins,isoprostanes,leukotrienes,tromboxanes) [ Time Frame: After treatment with pemirolast or matching placebo for 14-16 days ]
    Urine samples will be analysed with mass spectrometry (UPLC-MS/MS) and data presented as ng.mmol creatinine-1 for all metabolites

  2. Airway inflammation measured as the percentage of sputum eosinophils [ Time Frame: After treatment with pemirolast or matching placebo for 14-16 days ]
    Induced sputum will be collected 7 hours after the last inhaled allergen dose and percentage of eosinophils will be measured


Other Outcome Measures:
  1. Airway responsiveness expressed as methacholine PD20FEV1 [ Time Frame: After treatment with pemirolast or matching placebo for 14-16 days ]
    Change in methacholine responsiveness after the allergen challenge will be compared during the two treatment periods

  2. Measurement of inflammatory biomarkers in saliva [ Time Frame: After treatment with pemirolast or matching placebo for 14-16 days ]
    Saliva is collected before and after challenges to monitor activation of mast cells and other inflammatory pathways

  3. Measurement of biomarkers in blood [ Time Frame: After treatment with pemirolast or matching placebo for 14-16 days ]
    Venous blood samples are collected at clinic visits for asthma biomarkers. Biomarkers are taken before and after challenges according to sub-protocols specific for each analyte.

  4. Measurement of biomarkers in sputum [ Time Frame: After treatment with pemirolast or matching placebo for 14-16 days ]
    Sputum induction is performed on particular study days to assess inflammatory cell content and to collect sputum supernatant for analysis of biomarkers.

  5. Measurement of biomarkers in exhaled breath samples [ Time Frame: After treatment with pemirolast or matching placebo for 14-16 days ]
    Collection of exhaled air using the eNose will be used for exploratory studies of specific volatile and particular components of the exhaled breath



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-65 years inclusive
  • Diagnosed asthma as defined by at least one of the following:

    • response to standard asthma treatment
    • episodic wheezing
    • change in lung function over short periods of time
  • Non-smoker for the past two years and a total of smoking less than 5 pack-years
  • Stable intermittent asthma, only using bronchodilator therapy as needed for the last 4 weeks
  • FEV1 ≥ 75 % of predicted
  • A positive skin prick test to pollen (grass, birch, mugwort) or animal dander (dog, cat) and a history of associated symptoms on exposure.

Exclusion Criteria:

  • Any significant respiratory disease, other than asthma.
  • Subjects with seasonal asthma may not be included if they are in their season and subjects allergic to animal dander must not have a pet on their own or similar close exposure.
  • Use of:

    • Oral, injectable or inhaled glucocorticosteroid treatment for the last 4 weeks prior to inclusion or during the study
    • Inhaled long-acting β2-agonists, anticholinergic bronchodilators, antihistamines, theofyllines, nasal or inhaled cromones and antileukotrienes within 2 weeks of screening
    • Beta-blocking agents.
    • Immunomodulator drugs
    • NSAIDs.
  • Upper or lower respiratory tract infection within 4 weeks of screening
  • Females who are pregnant, intend to be or who are lactating. Female subjects of childbearing potential who are not willing to use adequate contraceptive methods (measures as required by local requirements or practice) during participation in the trial until at least three days after last intake of study treatments. Male subjects not surgically sterilized, who or whose partner is not using adequate contraceptive methods (measures as required by local requirements or practice) during participation in the trial until at least three days after last intake of study drug.
  • Subjects with BMI >30.
  • Evidence (from clinical laboratory tests, physical examination or medical history) of hepatic disease (other than Gilbert´s Syndrome)
  • Evidence (from physical examination or medical history) of any diseases that affects gastrointestinal absorption.
  • A diagnosis of brittle asthma (rapid fluctuations in disease severity).
  • Participation in other study in the four weeks prior to screening.
  • Evidence of drug or alcohol abuse.
  • History of having taken barbiturates or other drugs affecting the liver drug-metabolising enzymes within one month of the start of the trial.
  • Blood donor during the last four months prior to study start and throughout the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03119714


Contacts
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Contact: Barbro Dahlén, MD,PhD +46858586785 barbro.dahlen@ki.se
Contact: Nikolaos Lazarinis, MD +46768760476 nikolaos.lazarinis@ki.se

Locations
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Sweden
Lung and Allergy Research Unit C2-88 Karolinska University Hospital Huddinge Recruiting
Stockholm, Sweden, 14186
Contact: Barbro Dahlén, MD,PhD    +46858586785    barbro.dahlen@ki.se   
Contact: Nikolaos Lazarinis, MD    +46768760476    nikolaos.lazarinis@ki.se   
Sponsors and Collaborators
Karolinska University Hospital
Experimental Asthma and Allergy Research Unit, Karolinska Institutet
Unit for Chemistry II, Department of Medical Biochemistry, Karolinska Institutet
Occupational and Environmental Medicine, Sahlgrenska UH, Gothenburg
Div Clinical Pharmacology, Karolinska University Hospital
Dept. Respiratory Medicine, University of Amsterdam, Amsterdam
The Centre for Infection Medicine, Karolinska Institutet
Investigators
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Principal Investigator: Barbro Dahlén, MD,PhD Lung and Allergy Clinic, Karolinska UH

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Responsible Party: Barbro Dahlen, Professor, Karolinska University Hospital
ClinicalTrials.gov Identifier: NCT03119714     History of Changes
Other Study ID Numbers: PEMAG-2016-v2.3
First Posted: April 19, 2017    Key Record Dates
Last Update Posted: April 19, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Not planing to share data

Keywords provided by Barbro Dahlen, Karolinska University Hospital:
bronchoprovocation
early-late asthmatic reaction
mast cell stabilizer
mast cell mediators
sputum eosinophils

Additional relevant MeSH terms:
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Asthma
Lung Diseases, Obstructive
Lung Diseases
Bronchial Diseases
Respiratory Tract Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Pemirolast
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs