Effect of Fostair® on biomarkers of platelet adhesion in Idiopathic pulmonary fibrosis

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2013-004404-19-GB
• Date of registration: 25/03/2014
• Prospective Registration: Yes
• Primary sponsor: Hull and East Yorkshire Hospitals NHS Trust
• Public title: Effect of Fostair® on biomarkers of platelet adhesion in Idiopathic pulmonary fibrosis
• Scientific title: A Randomized, Double-blind, Placebo-controlled, Crossover Study to Assess the Effect of 28 Day Treatment with Fostair® pMDI 200/12 on biomarkers of platelet adhesion in Patients with Idiopathic pulmonary fibrosis. - Effect of Fostair® pMDI on biomarkers of platelet adhesion in IPF
• Date of first enrolment: 07/05/2014
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004404-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

United Kingdom

Contacts

• Name: Wright
• Affiliation: Hull and East Yorkshire Hospitals NHS Trust

• Name: Wright
• Affiliation: Hull and East Yorkshire Hospitals NHS Trust

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female subjects from 40 to 85 years of age
2. Diagnosis of definite IPF according to ATS/ERS Consensus Statement (2011) using either HRCT or surgical lung biopsy (SLB).
2.TLco of = 30 % predicted ( historical measure accepted as long as within the last year).
3. Able to maintain O2 saturation of = 89% while breathing room air at rest.
4. FVC of 50-80% predicted value
5. Negative serum pregnancy test at screening and negative urine pregnancy test at randomisation for female subjects of childbearing potential.
6. Competency to understand the information given in the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved Informed Consent Form (ICF); subjects must sign the form prior to the initiation of any study procedures, unless the assessment is performed as standard of care for this disease.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
1. Clinically significant respiratory diseases other than IPF, including asbestosis, other pneumoconiosis or hypersensitivity pneumonitis.
2. Clinically significant heart disease defined as a myocardial infarction documented by an ST elevation (STEMI) on electrocardiogram (ECG) within 6 months prior to screening, percutaneous coronary intervention or coronary artery bypass surgery within 6 months prior to screening, unstable angina pectoris, congestive heart failure (NYHA class III/IV or known left ventricular ejection fraction < 25%),ischaemic heart disease, right heart failure, significant right ventricular hypertrophy, or uncontrolled arrhythmia.
3. Current smokers
4. Use of any inhaled long acting beta-agonist or inhaled steroid within the 3 months prior to screening
5. Use of any medication to or possibly indicated in the treatment of IPF, such as pirfenidone, and oral corticosteroids.
6. Use of any Antiplatelet therapy which may alter assessment of study end points e.g. clopidogrel, Prasugrel, Dipyridamole etc.
7. History of cancer, precancerous state (eg, familial polyposis, BRCA1, BRCA2, carcinoma in-situ), other than non-melanomatous skin cancer, within 5 years prior to screening.
8. History or evidence of a clinically significant disorder, condition, or disease that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluations, procedures, or completion.
9. Participation in an investigational drug or device trial < 30 days prior to screening.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Idiopathic pulmonary fibrosis
MedDRA version: 16.1 Level: PT Classification code 10021240 Term: Idiopathic pulmonary fibrosis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Trade Name: Fostair
Pharmaceutical Form: Pressurised inhalation, solution
INN or Proposed INN: beclometasone dipropionate
CAS Number: 5534-09-8
Current Sponsor code: NA
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 400-
INN or Proposed INN: formoterol fumarate dihydrate
CAS Number: 183814-30-4
Current Sponsor code: NA
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 24-
Pharmaceutical form of the placebo: Pressurised inhalation, solution
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Main Objective: There is a significant unmet medical need for the treatment of Idiopathic pulmonary fibrosis (IPF); there is no effective therapy for treatment of IPF in the UK, and only pirfenidone is approved for treatment. The main goal of the current study is to evaluate the effect of Fostair on the biomarkers of platelet activation in IPF disease. We believe that platelets- cell fragments which have a major role in wound healing, also have a pivotal role in the pathogenesis of IPF and whether this translates in to a clinically beneficial effect of Fostair on IPF disease.

The primary objective of this study is to determine the effect of Fostair fine particle Metered dose inhaler on markers of pulmonary fibrosis. Primary endpoint will be a change in biomarkers of platelet activation.

Timepoint(s) of evaluation of this end point: Time points for evaluation will be at baseline visit, 4 weeks post initial treatment and the 4 weeks post second treatment

Primary end point(s): The primary outcome measure is the biomarkers for platelet adhesion. Measurements will include platelet-monocyte complex formation, platelet P-selectin expression and platelet fibrinogen binding in the presence of` the platelet agonists ADP ( Adenosine diphosphate) and TFLLR measured at baseline, and post IMP treatments at Visit 5 and visit 8.

Secondary Objective: Secondary end points: will be change in lung function as well as other clinical measures such as acute exacerbations, respiratory hospitalisations, six minute walking distance (6MWD), mean weekly activity as measured by a Sense wear® arm band, any change in sputum inflammatory cells, the alveolar fraction of exhaled NO, and quality of life as measured by KBILD questionnaire.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Evaluation of the secondary endpoints will occur at baseline, at visit 5 and at visit 8

Secondary end point(s): • Change in FVC % predicted from baseline will be expressed as mean (SD) and compared between the two treatment periods using paired ttest.

• Absolute change in 6MWD from baseline between treatment periods will be expressed as mean (SD) and compared between the two treatment periods using paired ttest.

•Compare Change in total score on K-BILD questionnaire from baseline between each treatment period and also change in the domains: breathlessness and activities (questions 1, 4, 11, 13), psychological (questions 3, 5, 6, 8, 10, 12, 14) and chest symptoms (questions 2, 7, 9); see Appendix 7
Scores will be compared using paired ttest a p<0.05 will be considered significant. The minimal important difference will also be identified a minimal important difference of 8 units will be considered significant.

•Change in Sputum inflammatory cells – inflammatory cell total and differential counts ( % neutrophils, eosinophils, macrophages, epithelial cells and lymphocytes) in sputum samples will be measured at baseline and following each treatment period. Results will be expressed as mean (SEM). For non-parametric data these will be log transformed and expressed as geometric mean (log SEM). Changes in these parameters from baseline will be measured using paired ttest where p<0.05 will be considered significant

• Change in FeNo
• Adjudicated acute exacerbations
• Adjudicated respiratory hospitalizations

Secondary ID(s)

Acadmed18013

NCT02048644

Source(s) of Monetary Support

chiesi ltd