Clinical Trials Register

Summary
EudraCT Number:	2014-004058-32
Sponsor's Protocol Code Number:	2014RESP02M(14-01-14)
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:	2015-06-12
Trial 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

2014-004058-32

A.3

Full title of the trial

The Efficacy and Mechanism Evaluation of Treating Idiopathic Pulmonary Fibrosis with the Addition of Co-trimoxazole (EME-TIPAC)

A.3.1

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

Treating pulmonary fibrosis with co-trimoxazole

A.3.2

Name or abbreviated title of the trial where available

Treating pulmonary fibrosis with co-trimoxazole

A.4.1

Sponsor's protocol code number

2014RESP02M(14-01-14)

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	Norfolk and Norwich University Hospital NHS Foundation Trust
B.1.3.4	Country
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	National Institute of Health Research
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Norfolk and Norwich University Hospital NHS Foundation Trust
B.5.2	Functional name of contact point	Lisa Chalkley
B.5.3	Address:
B.5.3.1	Street Address	Research Services Manager, R&D Department,Norfolk and Norwich University Hosp
B.5.3.2	Town/ city	Norwich
B.5.3.3	Post code	NR4 7UY
B.5.4	Telephone number	01603 286611
B.5.5	Fax number	01603 289800
B.5.6	E-mail	lisa.chalkley@nnuh.nhs.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	Cotrimoxazole
D.2.1.1.2	Name of the Marketing Authorisation holder	Chemidex Pharma limited trading as Essential Generics
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.3.1	Product name	Cotrimoxazole
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	trimethoprim
D.3.9.1	CAS number	738-70-5
D.3.9.2	Current sponsor code	none
D.3.9.3	Other descriptive name	none
D.3.9.4	EV Substance Code	AS2
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	80
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	sulphamethoxazole
D.3.9.1	CAS number	723-46-6
D.3.9.2	Current sponsor code	none
D.3.9.3	Other descriptive name	none
D.3.9.4	EV Substance Code	AS3
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	400
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	No
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	Tablet
D.8.4	Route of administration of the placebo	Oral 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

Pulmonary Fibrosis.

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	18.0
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

Does co-trimoxazole change the life expectancy and/or reduce the chances of being admitted to hospital or having a lung transplant for people with pulmonary fibrosis.

E.2.2

Secondary objectives of the trial

Does co-trimoxazole change how patients feel about their quality of life or their breathlessness and/or cough, their oxygen levels, breathing tests or blood biomarkers. Fifty patients will undergo a lung camera test (bronchoscopy) to obtain lung fluid samples to find out whether co-trimoxazole changes the numbers or amount of inflammatory cells, biomarkers and bacteria (using traditional and new techniques). The biomarkers will tell us about inflammation, lung damage and scar production. An additional objective is to find out whether the changes in inflammatory cells' biomarkers or bugs relate to the changes in clinical outcomes.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Male or female, aged greater than or equal to 40 years. IPF rarely occurs in individuals less than 40 years. Individuals younger than this more frequently have connective tissue related lung disease which is similar to but different from IPF.
2) A diagnosis of idiopathic pulmonary fibrosis (IPF) based on multi-disciplinary consensus according to the latest international guidelines within 2 years of enrolment into the study. Patients with a diagnosis of more than 2 years duration can be enrolled if they have evidence of progressive disease defined as ≥10% decline in forced vital capacity (FVC) or ≥15% decline in diffusing capacity of carbon monoxide over the preceding 6 or 12 months.
3) Patients may receive oral prednisolone up to a dose of 10 mg per day, anti-oxidant therapy, pirfenidone or other licensed medication for IPF e.g. nintedanib. Patients should be on a stable treatment regimen for at least 6 weeks to ensure baseline values are representative.
4) MRC dyspnoea score of greater than 1.
5) Able to provide informed consent.

E.4

Principal exclusion criteria

1) FVC > 70% predicted.
2) A recognised significant co-existing respiratory disease, defined as a respiratory condition that exhibits a greater clinical effect on respiratory symptoms and disease progression than IPF as determined by the principal investigator.
3) Patients with airways disease defined as forced expiratory volume in 1 second (FEV1)/FVC<60%
4) A self-reported respiratory tract infection within 4 weeks of screening defined as two or more of cough, sputum or breathlessness and requiring antimicrobial therapy.
5) Significant medical, surgical or psychiatric disease that in the opinion of the patient’s attending physician would affect subject safety or influence the study outcome including liver (Serum transaminase > 3 x upper limit of normal (ULN), Bilirubin > 2 x ULN) and renal failure (creatinine clearance <30ml/min).
6) Patients receiving recognised immunosuppressant medication (except prednisolone above) including azathioprine and mycophenolate mofetil.
7) Female subjects must be of non-childbearing potential, defined as follows: postmenopausal females who have had at least 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhoea with serum FSH>40mIU/ml or females who have had a hysterectomy or bilateral oophorectomy at least 6 weeks prior to enrolment.
8) Allergy or intolerance to trimethoprim or sulphonamides or their combination.
9) Untreated folate or B12 deficiency.
10) Known glucose-6-phosphate dehydrogenase (G6PD) deficiency or G6PD deficiency measured at screening in males of African, Asian or Mediterranean descent.
11) Receipt of an investigational drug or biological agent within the 4 weeks prior to study entry or 5 times the half-life if longer.

E.5 End points

E.5.1

Primary end point(s)

The time to death (all causes), lung transplant or the first non-elective hospital admission.

E.5.1.1

Timepoint(s) of evaluation of this end point

From randomisation of first patient until 12 months after the last patient is randomised, follow up is at 6 weeks, 3 months, 6 months, 9 months 12 months and then every 6 months.

E.5.2

Secondary end point(s)

Secondary efficacy outcomes
• Time from randomisation to death (all causes)
• Time from randomisation to first non-elective hospital admission for any reason
• Health related quality of life: (i)the King’s Brief Interstitial Lung Disease (K-BILD) health related quality of life questionnaire; (ii) the MRC Breathlessness Score; (iii) the EQ5D quality adjusted life year’s assessment, (iv) cough score
Lung function including assessment by spirometry and total lung diffusing capacity of carbon monoxide (DLCO)
Secondary outcome measures for safety
• Full blood count
• Urea and electrolytes
• Liver function
• Adverse Events including SAEs
Further exploratory and mechanistic outcomes
From the stored blood the proposed analyses, which is subject to change depending on the results of the bronchoscopy results.
• CRP as a measure of infection/inflammation;
• SP-D as a markers of epithelial injury;
• MMP-7 as a marker of disease severity;
• Neutrophil count

E.5.2.1

Timepoint(s) of evaluation of this end point

From randomisation of first patient until 12 months after the last patient is randomised, follow up is at 6 weeks, 3 months, 6 months, 9 months 12 months and then every 6 months.

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

E.6.4

Safety

E.6.5

Efficacy

Yes

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)

Yes

E.7.4

Therapeutic use (Phase IV)

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

Yes

E.8.1.6

Cross over

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in 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

Yes

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

12 months after the LVLS to enable data cleaning activities to be completed in all sites

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