Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

The following inclusion must be met for study entry (Part 1 - Screening):

Males and females between ≥ 18 and ≤ 65 years of age.
Able and willing to provide written informed consent to participate in the study, in accordance with ICH GCP requirements.
Non or ex-smoker, defined by an ex-smoker is defined as someone who completely stopped smoking for at least 12 months before Visit 1 of this study.
Able to adhere to study procedures.
In good general health without clinically significant medical history (see also Exclusion criteria below).
Physical examination and laboratory results within the normal ranges, if not within the ranges, they must be without clinically significance within 28 days prior to dosing.
Available for follow-up for the duration of the study (i.e. up to 10 weeks, including the Screening and Treatment Phases).
Mild to moderate, stable, allergic asthma by the ATS criteria (1)
History of episodic wheeze and shortness of breath; FEV1 at baseline at least 70% of the predicted value
Males agree to practice adequate contraception throughout the duration of the study and up to one month after drug administration.

FEMALE-SPECIFIC INCLUSION CRITERIA:

All females must have a negative serum pregnancy test at Screening Days -5 to -1 (Visit 5) and a negative urine pregnancy test at Day 1 of each Treatment Phase prior to dosing (Visits 6 and 11).

A female patient must meet one of the following criteria:

No reproductive potential, defined as: menopausal for at least two years or surgically sterile for at least six months (i.e. has undergone hysterectomy, bilateral oophorectomy or tubal ligation) OR
Participant agrees to be heterosexually inactive from Screening Visit 1 until one month post final dose OR
Participant agrees to consistently practice adequate contraception from Screening Visit 1 until one month post final dose by one of the following methods, two methods must be used if hormonal contraception is used: Contraceptive pills (stable dose for at least 2 months prior to dosing on Day 1 (Visit 6) or patch, Norplant or Provera; intrauterine device (IUD), condom with spermicide or diaphragm (cervical cap) with spermicide.

In addition the inclusion criteria above, the following inclusion criteria must be met for entry into the Dosing Phase (Part 2):

Positive methacholine challenge (PC20 ≤ 16 mg/ml)
Positive skin-prick test to common aeroallergens (including cat, dust mite, grass, pollen)
Positive allergen-induced early and late airway bronchoconstriction

Exclusion Criteria:

A patient will be excluded if one or more of the following conditions apply.

FEMALE ONLY EXCLUSIONS:

Females who are pregnant or are lactating
Females of childbearing potential who refuse to use an acceptable contraceptive regimen throughout the entire duration of the study (from the Screening visit until study completion) and for one month post dosing

RELEVANT MEDICAL HISTORY:

Use of any nicotine containing products within 12 months prior to Screening or a smoking history > 10 pack years
A worsening of asthma or a respiratory tract infection within 6 weeks preceding study entry

Clinically significant and relevant abnormal findings in the clinical history, physical examination, ECG, or laboratory tests during Screening that would interfere with the objectives of the study or that would in the Investigator's opinion preclude safe completion of the study. Abnormal clinical history and/or findings could include:

Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects
Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
Presence of out-of-range cardiac interval (PR < 110 msec, PR > 200 msec, QRS < 60 msec, QRS > 110 msec and QTc > 440 msec) on the screening ECG or other clinically significant ECG abnormalities
Autoimmune disease or immunodeficiency
History of clinically significant hypotensive episodes or symptoms of fainting, dizziness, or lightheadedness
Abnormal chest X-ray either at or within 1 year of Screening
Current acute or chronic illness (including infection) or recent recovery from acute illness which could, in the opinion of the Investigator, alter immune cell function (e.g., flu, cold or other respiratory infection, etc.)
Presence of a transplanted tissue or organ
Any evidence of malignancy [active and/or treated] within the previous five years or malignancy that is likely to recur during the period of the study
History of diabetes mellitus (Type I or II)
Thyroid disease (including thyroidectomy), requiring medication within the past 12 months
Asthma that is unstable or required emergent/urgent care, hospitalization or intubation during the past two years or that requires the use of oral or intravenous corticosteroids
Bleeding disorders (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
Major surgical procedure or significant traumatic injury within 12 months prior to the study treatment administration, OR minor surgery within one month prior to the study treatment administration or anticipation of the need for any surgery during the course of the study
Any other significant concomitant illness or injury that would interfere with the patient's participation in the study
Any clinically significant illness in the previous 28 days before the first day of dosing in either of the Treatment Phases of this study
Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and St John's Wort), in the previous 30 days before Day 1 of this study
History of drug abuse including marijuana, PCP, cocaine, crack, LSD or other identified street drugs
Positive results to HIV, HbsAg or anti-HCV tests at Screening
Lung disease other than mild to moderate allergic asthma
Concomitant disease or condition which could interfere with the conduct of the study, or for which the treatment might interfere with the conduct of the study, or which would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this study, including, but not limited to, cancer, alcoholism, drug dependency or abuse, or psychiatric disease
Recent (less than 1 year) history of alcohol dependency
Any other medical, social, or geographical factor, which would make it unlikely that the patient will comply with study procedures (e.g. history of non-compliance)

PROHIBITED MEDICATION USE

Systemic immunosuppressive or cytotoxic drug therapy (systemic corticosteroids, cyclophosphamide, methotrexate, cyclosporine, azathioprine, etc.) taken within two months prior to the study treatment administration. Corticosteroid nasal spray (e.g. for allergic rhinitis) or inhaled corticosteroid must have a 30 day washout prior to randomization (Visit 6)
Significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
Use of any investigational therapy or participation in another clinical study within 30 days prior to the study drug administration
Use of nonsteroidal anti-inflammatory drugs (NSAIDs) within 48 hr of dosing or aspirin within seven days of dosing and any time during the Treatment Phases
Have chronic use of any other medication for treatment of allergic lung disease other than short-acting ß2-agonists or ipratropium bromide
Use of caffeine-containing products or medications for 12 hr or alcohol or over the counter drugs including cold and allergy medications for 48 hr or inhaled bronchodilators for 8 hr prior to methacholine and allergen challenges