Clinical Trials Register

Summary
EudraCT Number:	2011-001063-43
Sponsor's Protocol Code Number:	11/0078
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-09-09
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

2011-001063-43

A.3

Full title of the trial

A Phase III single-blind, randomised, placebo controlled trial of long term therapy in patients with stable COPD using Moxifloxacin, Azithromycin, and Doxycycline: a Bayesian decision analysis, including other criteria, will be used to distinguish the optimal antibiotic treatment.

A.3.1

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

Development of an optimal antibiotic regime for long-term therapy in stable COPD

A.3.2

Name or abbreviated title of the trial where available

Development of an optimal antibiotic regime for long-term treatment in stable COPD

A.4.1

Sponsor's protocol code number

11/0078

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	University College London (UCL)
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	National Institute for 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	University College London (UCL)
B.5.2	Functional name of contact point	Alison Evans
B.5.3	Address:
B.5.3.1	Street Address	Joint Research Office, UCL, Gower Street,
B.5.3.2	Town/ city	London
B.5.3.3	Post code	WC1E 6BT
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	020 7679 6802
B.5.5	Fax number	02031082312
B.5.6	E-mail	a.j.evans@ucl.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	Avelox
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer HealthCare is the MAH for the Trade Name Avelox.In UK the MAH is Bayer plc,UK
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Avelox (Moxifloxacin)
D.3.2	Product code	N/A
D.3.4	Pharmaceutical form	Film-coated 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	moxifloxacin
D.3.9.1	CAS number	354812-41-2
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	N/A
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.IMP: 2
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	Azithromycin 250 - 1 A Pharma
D.2.1.1.2	Name of the Marketing Authorisation holder	1 A Pharma GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Azithromycin
D.3.4	Pharmaceutical form	Film-coated 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	Azithromycin
D.3.9.1	CAS number	83905-01-5
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	N/A
D.3.9.4	EV Substance Code	AS1
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	250
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.IMP: 3
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	Doxycyclin 100 - 1A Pharma
D.2.1.1.2	Name of the Marketing Authorisation holder	1A Pharma GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Doxycycline
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	Doxycycline
D.3.9.1	CAS number	564-25-0
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	N/A
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	100
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

COPD- Chronic Obstructive Pulmonary Disease

E.1.1.1

Medical condition in easily understood language

COPD is a name used to describe a collection of lung diseases where people have difficulty breathing because of long term damage to the airways in 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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10010952
E.1.2	Term	COPD
E.1.2	System Organ Class	100000004855

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The principal research question/objective is to identify the most effective antibiotic regime at reducing airway bacterial numbers in stable COPD patients in a developmental 13 week study, using three different antibiotic regimes together with a placebo. Safety outcomes will include bacterial resistance patterns, adverse events and tolerability of the regimes.

E.2.2

Secondary objectives of the trial

The secondary research questions/objectives of this study are to understand the following: To measure changes in spirometry (lung function measure), health status (by St. Georges Respiratory Questionnaire (SGRQ) and daily diary cards, and exacerbations (using daily diary cards). To assess patient adherence to 13 weeks antibiotic/placebo treatment.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

* Confirmed COPD diagnosis * Informed Consent: Patients must give their signed and dated written informed consent to participate * Gender: Male or female patients * Age: ≥ 45 years of age at screening * Produce sputum regularly (produce sputum in at least 3 months of a year) * Able to complete questionnaires for health status and symptoms and considered able to comply with the dosing regimen. * Severity of disease: Patients with a measured FEV1<80% of predicted normal values as determined at screening. * Woman of childbearing potential must show a negative urine pregnancy test and must be willing to use an effective method of contraception from the time consent is signed until (6 weeks) after treatment discontinuation.

E.4

Principal exclusion criteria

•Patients with Tuberculosis, other chronic respiratory disease (e.g. chronic asthma, bronchiectasis, pulmonary fibrosis), patients with hepatic or renal impairment and patients with prolonged QT interval and other cardiac abnormalities. •Patients with known hypersensitivity to the antibiotics under evaluation. •Patients on long term antibiotics for other conditions. •Patients with uncontrolled hypertension. •Female patients who are pregnant or planning on becoming pregnant during the study, or are breastfeeding. •Patients with a history of long QT syndrome or whose QTc measured at Visit 1 is prolonged (>450 msec for males and females) as confirmed by the ECG assessor. •Clinically relevant abnormal laboratory values at the screening assessment that could interfere with the objectives of the trial or safety of the volunteer. •Patient taking clinically significant contraindicated medication, as per the SmPCs

E.5 End points

E.5.1

Primary end point(s)

The primary outcome for this study is the 3 month fall in sputum bacterial load in patients with stable COPD. Sputum will be analysed for bacterial numbers by routine culture methods, and quantitative bacterial detection will be performed using PCR which provides a more accurate estimate of bacterial numbers. Safety outcomes will include bacterial resistance patterns, adverse events and tolerability of the regimes.

E.5.1.1

Timepoint(s) of evaluation of this end point

Analysis of bacterial numbers will be evaluated at week 14 (i.e. at the end of the trial) and compared to baseline.

E.5.2

Secondary end point(s)

Secondary end point include: •The number of exacerbations recorded from date of drug issue until date of end of treatment visit (week 14) (measured from daily diary cards/ recorded on CRFs) •Total and individual components separately (Symptoms, activity, impact) of St George’s Respiratory Questionnaire (SGRQ) score to measure health status, ranging from zero (no impairment) to 100 (maximum impairment). • EQ5D (A standardised instrument for use as a measure of health outcome in Work Package 5 (a future work package (study) investigating the cost-effectiveness of antibiotics in COPD patients) •Lung function (spirometry). • Antibiotic resistance measured from sputum based on standard NHS procedures (severe, intermediate, resistant) • Adherence (pill counts) Spirometry, resistance, SGRQ and EQ5D* will be measured and assessed at the end of the trial and compared to baselines taken prior to treatment. Adherence, including MAQ4 and MAQ8, will be measured and will form part of two inter-related studies in the future (WP5 and WP6).

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary end points will be evaluated at week 14 (i.e. at the end of the trial) and compared to baseline.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

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

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

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.8.3

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.8.4.1

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

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

The end of the trial will be defined as the date of the last hospital visit by the last study participant.

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1