A Phase IIa Randomized Double-blind Placebo-controlled Two-way Cross-over Trial of the Effects of Repeat Doses of 50 mg AXP1275 Daily on the Asthmatic Response to a Pulmonary Allergen Challenge in Adults With Mild-to-Moderate Atopic Asthma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 3
- 主要终点
- Late Asthmatic Response
研究概览
简要总结
This is the first study in human patients with asthma that the sponsor is conducting in order to evaluate if there are signals that the investigational medication, AXP1275, may be a safe and effective treatment for asthma. The results of this study may help the sponsor to design additional studies.
详细描述
This 2-way, randomized, double-blind crossover study in subjects with mild to moderate atopic asthma is designed to compare the responses to allergen and methacholine challenges within the same subject after approximately 2 weeks of treatment with AXP1275 50 mg or placebo. A total of 20 subjects with asthma with a dual (early and late) asthmatic response to an inhaled aeroallergen will be randomized to 1 of 2 treatment sequences (placebo then AXP1275 or AXP1275 then placebo) in a double-blind fashion to receive either oral AXP1275 or matching placebo, once-daily, for 14 days. The washout period between the 2 treatment periods will be 14 to 21 days.
A post-treatment follow-up visit will occur 14 ± 3 days after completion of the second treatment period.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 64 years (inclusive).
- •Male or female.
- •If male, is surgically sterile (vasectomy) or agrees to comply with required contraceptive measures.
- •If female, not pregnant (or lactating), as evidenced by a negative serum pregnancy test, and is either surgically sterile (hysterectomy, bilateral ovariectomy, or bilateral tubal ligation), or if a female of childbearing potential, agrees to comply with required contraceptive measures.
- •History of episodic wheeze and shortness of breath with a prebronchodilator FEV1 ≥70% of predicted at screening.
- •Asthma symptoms treated (if necessary) only with intermittent short-acting ß-agonist therapy by inhalation.
- •Demonstration of a positive wheal reaction on skin prick testing to at least 1 common aeroallergen at screening.
- •Screening inhalational allergen challenge response demonstrating that the subject experiences both an early asthmatic response (EAR) and a late asthmatic response (LAR).
- •Methacholine PC20 ≤16 mg/mL at screening.
- •No history of smoking within 6 months of screening, and with a total pack year history of ≤10 pack years.
- •12-lead ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the investigator.
- •All values for hematology, clinical chemistry, and urinalysis within the normal range, or if abnormal, are deemed not clinically significant by the investigator with documented agreement from the medical monitor.
- •Is able to give written informed consent.
排除标准
- •Past or present disease which, as judged by the investigator, may affect the outcome of this study.
- •Respiratory tract infection and/or exacerbation of asthma within 4 weeks prior to the screening period.
- •Symptomatic allergic rhinitis. Those subjects with a history of allergic rhinitis may participate if asymptomatic at screening (and continue to be so at baseline on Day 1 prior to dosing) and if, in the opinion of the investigator, it is unlikely that disease exacerbation will occur during the course of the study.
- •History of life-threatening asthma.
- •Abnormal chest X-ray.
- •Use of oral, injectable, or dermal steroids within 3 months and/or inhaled steroids within 1 month of screening.
- •Use of cromoglycate, nedocromil, leukotriene receptor antagonists (zafirlukast, pranlukast, montelukast), and inhibitors of 5-lipoxygenase (zileuton) within 4 weeks of screening.
- •Use of immunosuppressives, anticoagulants (warfarin or heparin), or any medications that may interact with pharmacodynamic (PD) effects of AXP1275 within 4 weeks of screening.
- •Use of theophylline-containing agents (any type) and long-acting β2-agonists (salmeterol, formoterol) within 4 weeks of screening.
- •Positive screen for drug(s) of abuse (opiates, methadone, cocaine, amphetamines, cannabinoids, barbiturates, or benzodiazepines) or cotinine.
- •Positive for hepatitis B surface antigen, hepatitis C virus, or human immunodeficiency virus (HIV) 1/
- •Has participated in a clinical trial and has received an investigational product within 30 days prior to screening, or 5 elimination half lives of the investigational product, whichever is longer.
- •Has had significant blood loss (>500 mL) or donation of blood within 2 months prior to screening visit
- •History of being unable to tolerate or complete methacholine or allergen challenge tests.
- •Subject is undergoing allergen desensitization therapy.
- •History of immunotherapy in the 3 years prior to screening or concurrently undergoing immunotherapy treatment.
- •Professional or ancillary personnel involved in the study.
- •Is not, in the opinion of the investigator, suitable for entry into the study.
研究组 & 干预措施
AXP1275
AXP1275 50 mg (2 × 25-mg capsules) once daily for 14 days
干预措施: AXP1275 (Drug)
AXP1275 matching placebo
AXP1275 matching placebo (2 capsules) once daily for 14 days
干预措施: AXP1275 matching placebo (Drug)
结局指标
主要结局
Late Asthmatic Response
时间窗: From 3 to 7 hours after allergen challenge on day 13 of both 14-day treatment periods
Area under the forced expiratory volume in 1 second (FEV1) curve from 3 to 7 hours after allergen challenge (AUC3-7h) on day 13 of both 14-day treatment periods.
次要结局
- Late Asthmatic Response-Secondary(Between 3 to 7 hours after allergen challenge on day 13 of both 14-day treatment periods)
- Sputum eosinophil count(On days 12, 13, and 14 of both 14-day treatment periods)
- Total Asthmatic Response(Between 0 to 7 hours after allergen challenge on day 13 of both 14-day treatment periods)
- Early Asthmatic Response(Between 0 to 2 hours after allergen challenge on day 13 of both 14-day treatment periods)
- FEV1 comparison(At day 12, 13, and 14 of both 14-day treatment periods)
- Sputum cell count (other)(On days 1, 12, 13, and 14 of both 14-day treatment periods)
- CCL13 and CCL17 concentrations(On days 12, 13, and 14 of both 14-day treatment periods)
- Maximum exhaled nitric oxide (eNO) and AUC of eNO(On days 13 and 14 of both 14-day treatment periods)
- eNO comparison(On days 13 and 14 of both 14-day treatment periods)
- Provocative concentration of methacholine(Between days 1 and 12 and between days 12 and 14 of both 14-day treatment periods)