Clinical Trials Register

Summary
EudraCT Number:	2011-004208-39
Sponsor's Protocol Code Number:	BAYq3939/15625
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-12-11
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2011-004208-39

A.3

Full title of the trial

Randomized, double-blind, placebo-controlled, multicEnter Study comParing CIprofloxacin DPI 32.5 mg BID intermittently administered for 28 days on / 28 days off or 14 days on / 14 days off versus placebo to evaluate the time to fiRst pulmonary exacErbation and frequency of exacerbations in subjects with non–cystic fibrosis bronchiectasis.

Studio randomizzato, in doppio cieco, controllato verso placebo, multicentrico, per confrontare Ciprofloxacina DPI 32,5 mg BID somministrata in modo intermittente (on-off) per 28 giorni / sospesa per 28 giorni, o somministrata per 14 giorni / sospesa per 14 giorni, rispetto a placebo, per valutare il tempo alla prima riacutizzazione polmonare e la frequenza delle riacutizzazioni in soggetti con bronchiectasia non da fibrosi cistica.

A.3.1

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

Ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis (non–CF BE)

Ciprofloxacina polvere secca per inalazione nella bronchiectasia non da fibrosi cistica (BE non FC)

A.3.2

Name or abbreviated title of the trial where available

RESPIRE 1

A.4.1

Sponsor's protocol code number

BAYq3939/15625

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	BAYER HEALTHCARE AG
B.1.3.4	Country	Germany
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	Bayer HealthCare AG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bayer HealthCare AG
B.5.2	Functional name of contact point	Clinical Trials Contact
B.5.3	Address:
B.5.3.1	Street Address	CTP Team / Ref:''EU CTR'' / Bayer Pharma AG
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	13342
B.5.3.4	Country	Germany
B.5.4	Telephone number	...
B.5.5	Fax number	...
B.5.6	E-mail	clinical-trials-contact@bayerhealthcare.com

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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/07/469
D.3 Description of the IMP
D.3.1	Product name	Ciprofloxacin DPI
D.3.2	Product code	BAYq3939
D.3.4	Pharmaceutical form	Inhalation powder, hard capsule
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	CIPROFLOXACIN
D.3.9.1	CAS number	85721-33-1
D.3.9.2	Current sponsor code	BAYq3939
D.3.9.4	EV Substance Code	SUB07470MIG
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	32.5
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	Inhalation powder
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

bronchiectasis

bronchiectasia

E.1.1.1

Medical condition in easily understood language

bronchiectasis: localized, irreversible dilation of part of the bronchial tree

bronchiectasia:localizzata,irreversibile dilatazione di parte dell'albero bronchiale

E.1.1.2

Therapeutic area

Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10006445
E.1.2	Term	Bronchiectasis
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objectives of the study are: • To evaluate the efficacy of ciprofloxacin DPI administered BID intermittently for 28 days on study treatment / 28 days off study treatment or 14 days on study treatment / 14 days off study treatment to prolong the time to first exacerbation requiring an intervention with systemic antibiotics in subjects with non CF BE. •To evaluate the efficacy of ciprofloxacin dry powder for inhalation (DPI) administered 2 times a day (BID) intermittently for 28 days on study treatment / 28 days off study treatment or 14 days on study treatment / 14 days off study treatment in reducing the frequency of pulmonary exacerbation requiring an intervention with systemic antibiotics in subjects with non–CF BEwithin 48 weeks after start of treatment.

Gli obiettivi primari di questo studio sono:• Valutare l’efficacia di ciprofloxacina polvere secca per inalazione(DPI, Dry Powder for Inhalation)somministrata due volte al giorno(BID, bis in die)in modo intermittente per 28 giorni di trattamento/sospesa per 28 giorni, oppure somministrata per 14 giorni di trattamento/sospesa per 14 giorni, nel prolungare il tempo alla prima riacutizzazione polmonare che richiede intervento con antibiotici sistemici (orali/e.v.), in soggetti con BE non FC.• Valutare l’efficacia di ciprofloxacina DPI somministrata due volte al giornoBID)in modo intermittente per 28 giorni di trattamento/sospesa per 28 giorni, oppure somministrata per 14 giorni di trattamento/sospesa per 14 giorni, nel ridurre la frequenza delle riacutizzazioni polmonari che richiedono intervento con antibiotici sistemici(orali/e.v.,in soggetti con BE non FC entro48 sett.dopol’inizio tratt

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are: •To assess pathogen eradication and acquisition of new pathogenic organisms not present at baseline; •To assess the safety and tolerability of different long term regimen of ciprofloxacin DPI; •To assess the improvement of quality of life by Saint George's Respiratory Questionnaire (SGRQ); •To assess changes in lung function as measured by change in FEV1.

Gli obiettivi secondari di questo studio sono: • Valutare l’eradicazione dei patogeni e l’acquisizione di nuovi organismi patogeni non presenti al basale; • Valutare la sicurezza e la tollerabilità di diversi regimi a lungo termine di ciprofloxacina DPI; • Valutare il miglioramento della qualità di vita mediante il Saint George’s Respiratory Questionnaire(SGRQ; • Valutare i cambiamenti della funzionalità polmonare, misurati in base alle variazioni del volume espirato forzato in 1 secondo (FEV1).

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

PHARMACOKINETIC/PHARMACODYNAMIC:
Vers:3.0
Date:2012/09/13
Title:Pharmacokinetic Sampling Manual
Objectives:Pharmacokinetics will be assessed on blood and sputum samples collected at baseline and at one other study visit, for a subset of subjects at selected sites. The subject will be asked to produce one to two sputum samples. Sampling should start after the administration of the study drug, with the first sample ideally approximately 2-4 h after theend of inhalation. All records identifying the patient will be kept confidential and, to the extent permitted by the applicable laws and/or regulations, will not be made publicly available. Rationale and procedures of Pharmacokinetics are described in the Pharmacokinetic Sampling Manual version 3.0 dated 13/Sep/2012

FARMACOCINETICA/FARMACODINAMICA:
Vers:3.0
Data:2012/09/13
Titolo:Manuale di raccolta dei campioni per le analisi di farmacocinetica
Obiettivi:La farmacocinetica sarà valutata per un sottoinsieme di soggetti in centri selezionati su campioni di sangue ed espettorato raccolti al basale e a un’altra visita di studio. I soggetti dovranno fornire da 1 a 2 campioni di espettorato. La raccolta dei campioni avrà luogo dopo la somministrazione del farmaco in studio, con il primo campione raccolto preferibilmente a circa 2-4 ore dal termine dell’inalazione. Tutta la documentazione in grado di rivelare l’identità del/la paziente sarà mantenuta riservata e, nella misura consentita dalle leggi e/o dalle normative applicabili, non sarà resa pubblica. Il razionale e le procedure di farmacocinetica sono descritti nel Manuale di raccolta dei campioni per le analisi di farmacocinetica, versione 3.0, del 13/set/2012.

E.3

Principal inclusion criteria

 Age >18 years;  Proven and documented diagnosis of non-CF idiopathic or postinfectious BE by both:  HRCT scan including 2 or more lobes and dilated airways compatible with BE at initial diagnosis; and  Positive culture from an adequate sputum sample for Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Streptococcus pneumoniae, Stenotrophomonas maltophilia or Burkholderia cepacia at screening and with history >=2 documented exacerbations in the past 12 months;  Stable pulmonary status as indicated by FEV1 (percent of predicted) >=30% and <90% (post-bronchodilator, if used as standard of treatment);  Stable regimen of standard treatment with: - Bronchodilators, anticholinergics, inhaled corticosteroids, or mucolytics, if used as chronic treatment for BE, at least for the past 4 weeks prior to screening; Subjects on maintenance therapy with low-dose systemic corticosteroids should be receiving <=10 mg/day prednisolone equivalent at least for the past 4 weeks before the screening visit; and/or - Macrolides if used as chronic treatment for BE for at least 6 months prior to screening;  Sputum production on the majority of days;  Ability to follow the inhaler device instructions;  Ability to complete questionnaires;  Written informed consent;  Negative urine pregnancy test result for women of childbearing potential before first dose of study drug;  Women of childbearing potential and men must agree to use adequate contraception when sexually active. This applies from the time of signing of the informed consent form (ICF) until 3 months after the last study drug administration. Adequate methods of contraception include vasectomy, or condom use, diaphragm with spermicidal gel, coil (intrauterine device), surgical sterilization, or oral contraceptives.

• Età >18 anni. • Diagnosi di bronchiectasia (BE) idiopatica non da fibrosi cistica (CF) o postinfettiva confermata e documentata da entrambi gli esami seguenti: • HRTC (TC ad alta risoluzione) di 2 o più lobi che evidenzia dilatazione delle vie aeree compatibile con la diagnosi iniziale di BE; e • coltura ottenuta da un campione di espettorato adeguato positiva ai batteri Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Streptococcus pneumoniae, Stenotrophomonas maltophilia o Burkholderia cepacia allo screening con >=2 esacerbazioni documentate negli ultimi 12 mesi. • Stato polmonare stabile come indicato da un FEV1 (percentuale del predetto) >=30% e <90% (post-broncodilatatore, se usato come trattamento standard). • Trattamento standard in regime stabile con: - broncodilatatori, anticolinergici, corticosteroidi per via inalatoria o mucolitici, se usati come trattamento cronico per la BE, da almeno 4 settimane prima dello screening; i soggetti in terapia di mantenimento con corticosteroidi per via sistemica a basso dosaggio devono ricevere <=10 mg/die di prednisolone equivalente da almeno 4 settimane prima della visita di screening; e/o - macrolidi, se usati come trattamento cronico per la BE, da almeno 6 mesi prima dello screening. • Produzione di espettorato nella maggioranza dei giorni. • Capacità di seguire le istruzioni per l’uso dell’inalatore. • Capacità di compilare questionari. • Consenso informato scritto. • Risultato negativo a un test di gravidanza su urine effettuato prima della prima somministrazione del farmaco in studio (per le pazienti in età fertile). • Le pazienti in età fertile e i pazienti, se sessualmente attivi/e, devono acconsentire a utilizzare un contraccettivo adeguato dal momento della firma del modulo di consenso informato (ICF) fino a 3 mesi dopo l’ultima somministrazione del farmaco in studio. I metodi di contraccezione adeguati includono vasectomia, preservativo, diaframma con gel spermicida, spirale (dispositivo intrauterino), sterilizzazione chirurgica o contraccettivi orali.

E.4

Principal exclusion criteria

 FEV1 <30% or >=90% predicted (post-bronchodilator);  Active allergic bronchopulmonary aspergillosis (ABPA);  Active and actively-treated non-tuberculosis mycobacterial (NTM) infection or tuberculosis;  Diagnosis of common variable immunodeficiency (CVID);  Recent significant hemoptysis (>=300 mL or requiring blood transfusion) in the preceding 4 weeks before screening (and during the screening period);  Primary diagnosis of COPD;  Known CF and / or documented chronic bronchial asthma;  Administration of any investigational drug within 4 weeks before screening; Medical history of allergies to quinolones or fluoroquinolones;  Women who are pregnant, lactating, or in whom pregnancy cannot be excluded;  History of tendon disease and other disorders related to quinolone treatment;  History of myasthenia gravis;  Concomitant administration of tizanidine while on study drug;  Systemic or inhaled antibiotic treatment for any indication within 4 weeks prior to the administration of study drug;except for chronic macrolide use  Systemic corticosteroids at >10 mg/day prednisolone equivalent for >14 days within 4 weeks prior to the administration of study drug; Previous assignment to treatment in this study (randomized in Study 15625).

• FEV1 <30% o >=90% del predetto (post-broncodilatatore). • Aspergillosi broncopolmonare allergica (ABPA) attiva. • Tubercolosi o infezione da micobatteri non tubercolari (NTM) in stato attivo e trattata. • Diagnosi di immunodeficienza variabile comune (CVID). • Recente emottisi significativa (>=300 mL o che necessita di trasfusione ematica) nelle 4 settimane precedenti lo screening (e durante il periodo di screening). • Diagnosi primaria di BPCO. • CF nota e/o asma bronchiale cronico documentato. • Assunzione di eventuali farmaci sperimentali nelle 4 settimane precedenti lo screening. • Anamnesi di allergie a chinoloni o fluorochinoloni. • Donne in gravidanza, allattamento o per le quali non sia possibile escludere una gravidanza. • Storia di tendinopatia o altri disturbi correlati al trattamento con chinoloni. • Storia di miastenia gravis. • Somministrazione concomitante di tizanidina durante il trattamento con il farmaco in studio. • Trattamento antibiotico per via sistemica o inalatoria per qualsiasi indicazione nelle 4 settimane precedenti la somministrazione del farmaco in studio; tranne che per l’uso di macrolidi. • Corticosteroidi per via sistemica alla dose di >10 mg/die di prednisolone equivalente per >14 giorni nelle 4 settimane precedenti la somministrazione del farmaco in studio. • Precedente assegnazione al trattamento previsto in questo studio (randomizzazione nello Studio 15625).

E.5 End points

E.5.1

Primary end point(s)

Time to first exacerbation Description: Exacerbation is defined by signs and symptoms plus intervention with systemic antibiotics

Tempo alla prima esacerbazione Descrizione: l’esacerbazione è definita da segni e sintomi e dall’uso di antibiotici per via sistemica

E.5.1.1

Timepoint(s) of evaluation of this end point

over 48 weeks after baseline

Fino a oltre 48 settimane dal basale

E.5.2

Secondary end point(s)

- Mean number of exacerbations per patient per 48 weeks; - Pathogens present at baseline and eradicated at 48 weeks; - Changes of Saint George's Respiratory Questionnaire (SGRQ) score from baseline to 48 weeks; - New pathogens at 48 weeks, not present at baseline; - Changes of forced expiratory volume in 1 second (FEV1) from baseline to 48 weeks; - Number of participants with adverse events as a measure of safety and tolerability.

Numero medio di esacerbazioni per paziente in 48 settimane; - Patogeni presenti al basale ed eradicati a 48 settimane; - Variazioni nel punteggio SGRQ (Saint George’s Respiratory Questionnaire) a 48 settimane rispetto al basale; - Patogeni nuovi, non presenti al basale, a 48 settimane; - Variazioni nel volume espiratorio forzato in 1 secondo (FEV1) a 48 settimane rispetto al basale; - Numero di partecipanti con eventi avversi come indice di sicurezza e tollerabilità.

E.5.2.1

Timepoint(s) of evaluation of this end point

respectively: - over 48 weeks after baseline - baseline and 48 weeks - baseline and 48 weeks - baseline and 48 weeks - baseline and 48 weeks - over 56 weeks after screening

rispettivamente:- fino a oltre 48 settimane dal basale - al basale e a 48 settimane - al basale e a 48 settimane - al basale e a 48 settimane - al basale e a 48 settimane - a oltre 56 settimane dallo screening

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

Yes

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)

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Argentina

Australia

Brazil

Israel

Japan

New Zealand

United States

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

''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

Number of subjects for this age range:

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.1.2.1

Number of subjects for this age range:

150

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

150

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

105

F.4.2.2

In the whole clinical trial

300

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)

None

Nessuno

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

2013-01-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-11-22

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-03-09

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials