Clinical trial NCT01890161: A Phase IIa Repeat Dose AXP1275 vs Placebo Cross-over Trial With Pulmonary Allergen Challenge in Adults With Asthma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atopic Asthma
Keywords: asthma
Lead sponsor: Axikin Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2013-07-01
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Age 18 to 64 years (inclusive).
2. Male or female.
3. If male, is surgically sterile (vasectomy) or agrees to comply with required contraceptive measures.
4. 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.
5. History of episodic wheeze and shortness of breath with a prebronchodilator FEV1 ≥70% of predicted at screening.
6. Asthma symptoms treated (if necessary) only with intermittent short-acting ß-agonist therapy by inhalation.
7. Demonstration of a positive wheal reaction on skin prick testing to at least 1 common aeroallergen at screening.
8. Screening inhalational allergen challenge response demonstrating that the subject experiences both an early asthmatic response (EAR) and a late asthmatic response (LAR).
9. Methacholine PC20 ≤16 mg/mL at screening.
10. No history of smoking within 6 months of screening, and with a total pack year history of ≤10 pack years.
11. 12-lead ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the investigator.
12. 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.
13. Is able to give written informed consent.

Exclusion Criteria:

1. Past or present disease which, as judged by the investigator, may affect the outcome of this study.
2. Respiratory tract infection and/or exacerbation of asthma within 4 weeks prior to the screening period.
3. 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.
4. History of life-threatening asthma.
5. Abnormal chest X-ray.
6. Use of oral, injectable, or dermal steroids within 3 months and/or inhaled steroids within 1 month of screening.
7. Use of cromoglycate, nedocromil, leukotriene receptor antagonists (zafirlukast, pranlukast, montelukast), and inhibitors of 5-lipoxygenase (zileuton) within 4 weeks of screening.
8. Use of immunosuppressives, anticoagulants (warfarin or heparin), or any medications that may interact with pharmacodynamic (PD) effects of AXP1275 within 4 weeks of screening.
9. Use of theophylline-containing agents (any type) and long-acting β2-agonists (salmeterol, formoterol) within 4 weeks of screening.
10. Positive screen for drug(s) of abuse (opiates, methadone, cocaine, amphetamines, cannabinoids, barbiturates, or benzodiazepines) or cotinine.
11. Positive for hepatitis B surface antigen, hepatitis C virus, or human immunodeficiency virus (HIV) 1/2.
12. 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.
13. Has had significant blood loss (\>500 mL) or donation of blood within 2 months prior to screening visit 1.
14. History of being unable to tolerate or complete methacholine or allergen challenge tests.
15. Subject is undergoing allergen desensitization therapy.
16. History of immunotherapy in the 3 years prior to screening or concurrently undergoing immunotherapy treatment.
17. Professional or ancillary personnel involved in the study.
18. Is not, in the opinion of the investigator, suitable for entry into the study.

Primary outcomes:
measure: Late Asthmatic Response
timeFrame: From 3 to 7 hours after allergen challenge on day 13 of both 14-day treatment periods
Secondary outcomes:
measure: Early Asthmatic Response
timeFrame: Between 0 to 2 hours after allergen challenge on day 13 of both 14-day treatment periods
measure: Late Asthmatic Response-Secondary
timeFrame: Between 3 to 7 hours after allergen challenge on day 13 of both 14-day treatment periods
measure: Total Asthmatic Response
timeFrame: Between 0 to 7 hours after allergen challenge on day 13 of both 14-day treatment periods
measure: FEV1 comparison
timeFrame: At day 12, 13, and 14 of both 14-day treatment periods
measure: Sputum eosinophil count
timeFrame: On days 12, 13, and 14 of both 14-day treatment periods
measure: Sputum cell count (other)
timeFrame: On days 1, 12, 13, and 14 of both 14-day treatment periods
measure: CCL13 and CCL17 concentrations
timeFrame: On days 12, 13, and 14 of both 14-day treatment periods
measure: Provocative concentration of methacholine
timeFrame: Between days 1 and 12 and between days 12 and 14 of both 14-day treatment periods
measure: Maximum exhaled nitric oxide (eNO) and AUC of eNO
timeFrame: On days 13 and 14 of both 14-day treatment periods
measure: eNO comparison
timeFrame: On days 13 and 14 of both 14-day treatment periods
Other outcomes:
measure: Adverse events (AEs)
timeFrame: Throughout both 14-day treatment periods
measure: Clinical laboratory, vital signs, physical examination, and ECG changes
timeFrame: Baseline to the end of the study (14 +/- 3 days from the last of two treatments)
measure: AXP1275 plasma concentrations
timeFrame: day 6 or 7 (predose), day 12 (3 hr post dose), day 13 (3 and 10 hr post dose), and day 14 (3 hr post dose) for the active treatment arm
Locations:
city: Vancouver
country: Canada
facility: Vancouver General Hospital, The Lung Centre
state: British Columbia
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Quebec
country: Canada
facility: IUCPQ, Institut de cardiologie et de pneumologie de l'Hôpital Laval
Study officials:
affiliation: McMaster University
name: Paul O'Byrne, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IUCPQ, Institut de cardiologie et de pneumologie de l'Hôpital Laval
name: Louis-Philippe Boulet, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia, Vancouver General Hospital
name: Mark Fitzgerald, MD
role: PRINCIPAL_INVESTIGATOR
References: