A Phase IIa Repeat Dose AXP1275 vs Placebo Cross-over Trial With Pulmonary Allergen Challenge in Adults With Asthma

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.

Inclusion criteria

• 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.

Exclusion criteria

• 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) 1/2.
• 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 1.
• 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.