Clinical Trials Register

Summary
EudraCT Number:	2007-006096-37
Sponsor's Protocol Code Number:	BAY 12-8039/11980
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-03-12
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2007-006096-37

A.3

Full title of the trial

A prospective, multinational, multicenter, randomized, double-blind, double-dummy, controlled study comparing the efficacy and safety of moxifloxacin to that of amoxicillin-clavulanic acid for the treatment of subjects with acute exacerbations of chronic bronchitis: MAESTRAL (moxifloxacin in AECB superiority trial)

A.3.2

Name or abbreviated title of the trial where available

MAESTRAL

A.4.1

Sponsor's protocol code number

BAY 12-8039/11980

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

none

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Bayer HealthCare AG, Leverkusen, Germany
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Avalox p.o. (film coated tablet)
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Vital 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	moxifloxacin
D.3.2	Product code	BAY12-8039
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	186826-86-8
D.3.9.2	Current sponsor code	BAY12-8039
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Yes
D.3.11.13.1	Other medicinal product type	anti-infective
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Amoxi-Clavulan STADA 875/125 mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	STADApharm 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	amoxicillin and clavulanic acid
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	amoxicillin
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	875
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	clavulanic acid
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	125
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Yes
D.3.11.13.1	Other medicinal product type	anti-infective

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	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated 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

acute exacerbation of chronic bronchitis

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10000743
E.1.2	Term	Acute exacerbation of chronic bronchitis

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 primary objective is to compare the efficacy of moxifloxacin 400 mg PO OD for five days with the respective efficacy of amoxicillin clavulanic acid 875/125 mg PO BID for seven days in the treatment of subjects with AECB. The primary efficacy endpoint will be clinical failure rates at 8 weeks post-therapy visit in outpatients with AECB. Clinical failure is defined as the requirement for additional or alternate treatment (including increased dose or duration of treatment) for an exacerbation of respiratory symptoms, with systemic antibiotics and/or systemic corticosteroids and/or hospitalization with systemic antibiotic and/or systemic corticosteroid administration within 8 weeks post therapy.

E.2.2

Secondary objectives of the trial

The secondary objectives will compare the following between the two treatment groups: •Clinical failure rates •Bacteriological eradication rates •Clinical failure rates (for subjects with positive sputum culture at enrollment; for each stratum) •Weekly mean symptom scores measured by the AECB-Symptom Scale (AECB-SS) •Rates and speed of symptom relief measured by the AECB-SS •Need for any change in dosage or additional respiratory medication such as bronchodilators and inhaled steroids, excluding short acting bronchodilators •Improvement in symptom burden measured by the AECB-SS •Improvement in health-related QoL measured by The St. George’s Hospital Respiratory Questionnaire (SGRQ) •Spirometry tests will be compared between treatment groups at each assessment visit •Healthcare resource utilization/consumption related to chronic bronchitis management •Safety and tolerability of moxifloxacin versus amoxicillin clavulanic acid, with particular attention to rates of diarrhea

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Outpatients with chronic bronchitis
2.Male or female subjects, greater than or equal to 60 years old
3.Subject who can be managed with oral antimicrobials
4.Post bronchodilatory FEV1 less than or equal to 60% predicted and FEV1/FVC less than 70% at enrollment.
5.Documented history of 2 or more AECB episodes, within 12 months of study enrollment, requiring a course of systemic antibiotics and/or systemic corticosteroids 6.All symptoms/signs must be present and confirmed by the Investigator: •Increase in dyspnea •Purulent sputum •Increase in sputum volume
7.Subject must provide a sputum sample. The sputum will be assessed macroscopically by the investigator and should be graded as either yellow, green or rust (according to the provided color chart).
8.Current or past cigarette smoker with great than or equal to 20 pack year smoking history
9.Subjects must be exacerbation-free for at least 30 days prior to enrollment
10.Subjects must be willing and able to complete the questionnaires and subject booklet without assistance
11.Subjects with medical conditions and social status at the time of enrollment compatible with study protocol procedures
12.Willing and able to provide written informed consent

E.4

Principal exclusion criteria

1.Known hypersensitivity to quinolones, ß-lactams, or to any of the excipients of the study drugs
2.Pregnant or breast feeding women (women of childbearing potential, based on investigator assessment must have negative urinary pregnancy test)
3.Known to have congenital or acquired QT prolongation
4.Known to have clinically relevant bradycardia
5.Known to have clinically relevant heart failure with reduced left ventricular ejection fraction
6.Known to have previous history of symptomatic arrhythmias
7.Taking QT prolonging drugs, for example class IA or III antiarrhythmic agents (e.g., quinidine, procainamide, amiodarone, sotalol), neuroleptics (e.g., phenothiazines, pimozide, sertindole, haloperidol, sultopride), tricyclic antidepressants, certain antihistaminics (e.g., terfenadine, astemizole, mizolastine), certain antimicrobials (sparfloxacin, erythromycin IV, pentamidine, antimalarials particularly halofantrine) or other QT prolonging drugs (e.g., cisapride, vincamine iv, bepridil, and diphemanil)
8.Known electrolyte disturbances that are not controlled, particularly uncorrected hypokalemia
9.Known history of hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption
10.History of a tendon disease/disorder
11.Known history of liver dysfunction (Child-Pugh C), including known elevated transaminases (ALT and/or AST greater than 5 times the upper limit of normal)
12.Known severe renal impairment with glomerular filtration rate of <30mL/min
13.Known neutropenia (neutrophil count <1000/mm3) caused by immunosuppressive therapy or malignancy
14.Known to have AIDS (CD4 count of <200/mm3), or be HIV positive and receiving Highly Active Anti-Retroviral Therapy (HAART) (HIV testing is not mandatory)
15.Known chronic asthma (>15% reversibility or at least 200 mL), bronchial carcinoma, active pulmonary tuberculosis, known diffuse bronchiectasis, cystic fibrosis, or pneumonia (a chest X-ray is not mandatory)
16.Known history of chronic colonization of pathogenic organisms resistant to moxifloxacin and/or amoxicillin clavulanic acid (e.g., Pseudomonas aeruginosa, MRSA)
17.Receiving long term (>4 consecutive weeks) systemic corticosteroid treatment (>10 mg/day of prednisolone or equivalent)
18.Received short course of systemic corticosteroid treatment within 30 days prior to enrollment
19.Unable to take oral medication
20.Life expectancy of less than 6 months
21.Receiving systemic antibacterial therapy within 30 days prior to study enrollment
22.Requiring concomitant systemic antibacterial agents
23.Use of any investigational drug or device within 30 days of screening, or previously enrolled in this study
24.Requiring home ventilatory support (subjects requiring home/portable oxygen therapy or CPAP for sleep apnea are not excluded) and/or those who have a tracheotomy in situ
25.History of liver function disorders following previous treatment with amoxicillin-clavulanic acid
26. Receiving disulfiram therapy

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy criterion are clinical failure rates at the follow-up visit 8 weeks after end of treatment. Clinical failure is defined as the requirement for additional or alternate treatment (including increased dose or duration of treatment) for an exacerbation of respiratory symptoms, with systemic antibiotics, and/or systemic corticosteroids, and/or hospitalization with systemic antibiotic and/or systemic corticosteroid administration within 8 weeks post therapy.

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

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

Yes

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

double-dummy

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

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.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

109

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

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 study is defined as clean database.

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.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

500

F.4.2.2

In the whole clinical trial

1350

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After the subject has ended his/her participation in the trial, he/she is treated according to local medical practice.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2008-03-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-04-04

P. End of Trial
P.	End of Trial Status	Completed

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