Clinical Trials Register

Summary
EudraCT Number:	2013-004404-19
Sponsor's Protocol Code Number:	Acadmed18013
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-03-25
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2013-004404-19

A.3

Full title of the trial

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.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.3.2

Name or abbreviated title of the trial where available

Effect of Fostair® pMDI on biomarkers of platelet adhesion in IPF

A.4.1

Sponsor's protocol code number

Acadmed18013

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02048644

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Hull and East Yorkshire Hospitals NHS Trust
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	chiesi ltd
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Hull and East Yorkshire Hospitals NHS Trust
B.5.2	Functional name of contact point	Wright
B.5.3	Address:
B.5.3.1	Street Address	Respiratory Medicine
B.5.3.2	Town/ city	Castle Hill Hospital, Cottingham
B.5.3.3	Post code	HU16 5JQ
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01482624067
B.5.5	Fax number	01482624068
B.5.6	E-mail	c.e.wright@hull.ac.uk

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Fostair
D.2.1.1.2	Name of the Marketing Authorisation holder	Chiesi Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Pressurised inhalation, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	beclometasone dipropionate
D.3.9.1	CAS number	5534-09-8
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	400
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	formoterol fumarate dihydrate
D.3.9.1	CAS number	183814-30-4
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	AS2
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	24
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Pressurised inhalation, solution
D.8.4	Route of administration of the placebo	Inhalation use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Idiopathic pulmonary fibrosis

E.1.1.1

Medical condition in easily understood language

chronic fibrosis of the lung

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	PT
E.1.2	Classification code	10021240
E.1.2	Term	Idiopathic pulmonary fibrosis
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

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.

E.2.3

Trial contains a sub-study

E.3

Principal 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.

E.4

Principal 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.

E.5 End points

E.5.1

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.

E.5.1.1

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

E.5.2

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

E.5.2.1

Timepoint(s) of evaluation of this end point

Evaluation of the secondary endpoints will occur at baseline, at visit 5 and at visit 8

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1