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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Bronchoconstriction measured as fall in FEV1 during the early (EAR) and late (LAR) asthmatic reaction induced by allergen
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
- •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
- •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 >
- •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.
研究组 & 干预措施
Pemirolast
Pemirolast 200mg bid 14-16 days
干预措施: Pemirolast (Drug)
Placebo Oral Tablet
Matching placebo bid 14-16 days
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Bronchoconstriction measured as fall in FEV1 during the early (EAR) and late (LAR) asthmatic reaction induced by allergen
时间窗: After treatment with pemirolast or matching placebo for 14-16 days
次要结局
- Mast cell activation measured as urinary excretion of metabolites of lipid mediators (prostaglandins,isoprostanes,leukotrienes,tromboxanes)(After treatment with pemirolast or matching placebo for 14-16 days)
- Airway inflammation measured as the percentage of sputum eosinophils(After treatment with pemirolast or matching placebo for 14-16 days)
研究者
Barbro Dahlen
Professor
Karolinska University Hospital