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

• ClinicalTrials.gov Identifier: NCT01343745
• Recruitment Status: Completed
• First Posted: April 28, 2011
• Last Update Posted: April 13, 2018
• Sponsor: Chiesi Farmaceutici S.p.A.
• Information provided by (Responsible Party): Chiesi Farmaceutici S.p.A.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Mild Persistent Asthma	Drug: BDP/formoterol; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• 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)
• Study Start Date: February 2008
• Actual Primary Completion Date: August 2008
• Actual Study Completion Date: August 2008

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Placebo pMDI	Drug: Placebo; pressurised metered dose inhaler
Experimental: Low dose; BDP/formoterol pMDI low dose	Drug: BDP/formoterol; pressurised metered dose inhaler, BDP + Formoterol 100/6 µg, 1 inhalation bid (total daily dose 200 µg BDP + 12 µg formoterol); Other Name: Foster
Experimental: High dose; BDP/Formoterol pMDI high dose	Drug: BDP/formoterol; pressurised metered dose inhaler, BDP + Formoterol 100/6 µg, 4 inhalations bid (total daily dose 800 µg BDP + 48 µg formoterol); Other Name: Foster

Outcome Measures

Primary Outcome Measures :

1. PC20 after AMP challenge [ Time Frame: 4 h post dose ]
   Provocative Concentration of AMP causing a 20% fall in FEV1.
2. Fractional Exhaled Nitric Oxide (FeNO) [ Time Frame: 4 h post dose ]
   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.
3. Lung function [ Time Frame: from 0 to 4 h post dose ]
   FEV1 area under the curve from 0 to 4 hour post dose (AUC0-4h)

Secondary Outcome Measures :

1. FENO [ Time Frame: 2 h post dose ]
   Fractional exhaled nitric oxide

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male and female patients 18-50 years of age, who have signed an informed consent form.
2. Clinical evidence of asthma
3. Steroid naïve asthmatic patients
4. FEV1 at Screening Visit is >70 % of the predicted value and at least 2.0 L.
5. Body Mass Index between 18 and 35.
6. Sensitivity to AMP at Screening Visit.
7. FENO levels >25 ppb at the Screening Visit

Exclusion Criteria:

1. Having received an investigational product within 2 months of Screening Visit.
2. Inability to comply with study procedures or with study treatment intake.
3. Any significant lung disease which is considered by the investigator to be clinically significant.
4. Patients who suffer from Chronic Obstructive Pulmonary Disease (COPD)
5. Previous or current smokers who have a smoking history greater than 5 pack years.
6. 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.
7. Patients with QTc >450msec at the Screening Visit.
8. Patients with serum potassium <3.5 mEq/L or >6 mEq/L.
9. Intolerance/hypersensitivity or any contra-indication to treatment with beta2-agonists and/or inhaled corticosteroids.
10. Patients who have a history of alcohol or substance abuse that in the opinion of the Investigator may be of clinical significance.
11. Patients who have undergone major surgery in the previous 3 months.
12. Patients who have had an exacerbation of asthma, requiring treatment with oral steroids during the last month prior to Screening Visit.
13. Patients treated with slow-release corticosteroids 2 months prior to Screening Visit.
14. Patients currently treated with anti-IgE Antibodies.
15. Patients who have had a respiratory tract infection within 4-weeks prior to Screening Visit.
16. Females not willing to use effective contraceptive measures such as oral contraceptive or intra-uterine device (IUD).
17. Females who are pregnant, lactating or planning to become pregnant

Contacts and Locations

Locations

United Kingdom

Respiratory Clinical Trials - Heart Lung Centre - Queen Anne Street Medical Centre

London, United Kingdom, W1G 8HU

Sponsors and Collaborators

Chiesi Farmaceutici S.p.A.

Investigators

• Principal Investigator: Brian J O'Connor, MD; Heart Lung Centre

More Information

Additional Information:

Study Record on EU Clinical Trials Register including results 

Publications of Results:

O'Connor BJ, Collarini S, Poli G, Brindicci C, Spinola M, Acerbi D, Barnes PJ, Leaker B. Rapid effects of extrafine beclomethasone dipropionate/formoterol fixed combination inhaler on airway inflammation and bronchoconstriction in asthma: a randomised controlled trial. BMC Pulm Med. 2011 Dec 21;11:60. doi: 10.1186/1471-2466-11-60.

• Responsible Party: Chiesi Farmaceutici S.p.A.
• ClinicalTrials.gov Identifier: NCT01343745
• Other Study ID Numbers: FB/PS/14/169/07; 2007-004345-14 ( EudraCT Number )
• First Posted: April 28, 2011
• Last Update Posted: April 13, 2018
• Last Verified: April 2018

Additional relevant MeSH terms:

Formoterol Fumarate; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action