Dose Response AMP Challenge Study With Beclometasone Dipropionate (BDP)/Formoterol Pressurised Metered Dose Inhaler (pMDI)

Study Overview
=================
Brief Summary
-----------------
The aim of this exploratory investigation is to evaluate if the Forced Expiratory Volume in the 1st second (FEV1) measurements, fractional exhaled nitric oxide (FENO) and Provocative Concentration 20 (PC20) after Adenosine Monophosphate (AMP) bronchial challenge evaluated after administration of a fixed combination of a Long-acting Beta-2-agonist (LABA) and an Inhaled Corticosteroid (ICS) at increasing doses may be suitable to demonstrate a dose response.

Official Title
-----------------
Dose Response Evaluation of CHF 1535 HFA pMDI in Asthmatic Patients Using Lung Function, Adenosine Monophosphate Bronchial Challenge and Fractional Exhaled Nitric Oxide (FENO)

Conditions
-----------------
Mild Persistent Asthma

Intervention / Treatment
-----------------
* Drug: BDP/formoterol
* Drug: BDP/formoterol
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female patients 18-50 years of age, who have signed an informed consent form. Clinical evidence of asthma Steroid naïve asthmatic patients FEV1 at Screening Visit is >70 % of the predicted value and at least 2.0 L. Body Mass Index between 18 and 35. Sensitivity to AMP at Screening Visit. FENO levels >25 ppb at the Screening Visit Exclusion Criteria: Having received an investigational product within 2 months of Screening Visit. Inability to comply with study procedures or with study treatment intake. Any significant lung disease which is considered by the investigator to be clinically significant. Patients who suffer from Chronic Obstructive Pulmonary Disease (COPD) Previous or current smokers who have a smoking history greater than 5 pack years. Patients with any uncontrolled disease that might, in the judgment of the investigator, place the patients at undue risk or potentially compromise the results or interpretation of the study. Patients with QTc >450msec at the Screening Visit. Patients with serum potassium <3.5 mEq/L or >6 mEq/L. Intolerance/hypersensitivity or any contra-indication to treatment with beta2-agonists and/or inhaled corticosteroids. Patients who have a history of alcohol or substance abuse that in the opinion of the Investigator may be of clinical significance. Patients who have undergone major surgery in the previous 3 months. Patients who have had an exacerbation of asthma, requiring treatment with oral steroids during the last month prior to Screening Visit. Patients treated with slow-release corticosteroids 2 months prior to Screening Visit. Patients currently treated with anti-IgE Antibodies. Patients who have had a respiratory tract infection within 4-weeks prior to Screening Visit. Females not willing to use effective contraceptive measures such as oral contraceptive or intra-uterine device (IUD). Females who are pregnant, lactating or planning to become pregnant

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo pMDI | Drug: Placebo<br>* pressurised metered dose inhaler<br>|
| Experimental: Low dose<br>BDP/formoterol pMDI low dose | Drug: BDP/formoterol<br>* pressurised metered dose inhaler, BDP + Formoterol 100/6 µg, 1 inhalation bid (total daily dose 200 µg BDP + 12 µg formoterol)<br>* Other names: Foster;|
| Experimental: High dose<br>BDP/Formoterol pMDI high dose | Drug: BDP/formoterol<br>* pressurised metered dose inhaler, BDP + Formoterol 100/6 µg, 4 inhalations bid (total daily dose 800 µg BDP + 48 µg formoterol)<br>* Other names: Foster;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PC20 after AMP challenge | Provocative Concentration of AMP causing a 20% fall in FEV1. | 4 h post dose | 
| Fractional Exhaled Nitric Oxide (FeNO) | Fractional exhaled nitric oxide (ppb). FeNO is a biomarker measured in a breath test and it is a validated method for measuring the airway inflammation in asthma. | 4 h post dose | 
| Lung function | FEV1 area under the curve from 0 to 4 hour post dose (AUC0-4h) | from 0 to 4 h post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FENO | Fractional exhaled nitric oxide | 2 h post dose |