Clinical Trials Register

Summary
EudraCT Number:	2011-005187-25
Sponsor's Protocol Code Number:	BUC-SI-11-001
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:	2012-03-19
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2011-005187-25

A.3

Full title of the trial

Efficacy and tolerability clinical trial of an immunostimulant made from inactivated bacteria (BUCCALIN) in the prophylaxis of infection of the airways (rhinotracheobronchitis, colds). Double-blind multicenter, randomized study vs. placebo.

Studio clinico sull’efficacia e la tollerabilita' di un immunostimolante a base di batteri inattivati (BUCCALIN) nella profilassi degli episodi infettivi delle vie aeree (rinotracheobronchiti, malattie da raffreddamento). Studio in doppio cieco vs placebo, randomizzato, multicentrico.

A.3.1

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

Efficacy and tolerability clinical trial of BUCCALIN in the prophylaxis of respiratory infections.

Studio clinico atto a valutare l'efficacia e la tollerabilita' di BUCCALIN nella profilassi delle infezioni respiratorie.

A.3.2

Name or abbreviated title of the trial where available

BUC-SI-11-001

A.4.1

Sponsor's protocol code number

BUC-SI-11-001

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	SOCIETA' LABORATORIO FARMACEUTICO S.I.T. SRL
B.1.3.4	Country	Italy
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	Laboratorio Farmaceutico S.I.T. S.r.l.
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	Medi Service SRL
B.5.2	Functional name of contact point	Ricerca Clinica
B.5.3	Address:
B.5.3.1	Street Address	Via G. Matteotti, 43/B
B.5.3.2	Town/ city	Agrate Brianza
B.5.3.3	Post code	20864
B.5.3.4	Country	Italy
B.5.4	Telephone number	039 6057074
B.5.5	Fax number	039 6057319
B.5.6	E-mail	medi@mediservice.it

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	BUCCALIN*AD 7CPR 0,2G
D.2.1.1.2	Name of the Marketing Authorisation holder	SIT LABORATORIO FARMAC. Srl
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Gastro-resistant 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	ALLERGENS, BACTERIA
D.3.9.1	CAS number	8000045-24-1
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	SUB12782MIG
D.3.10	Strength
D.3.10.1	Concentration unit	million organisms million organisms
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
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	Gastro-resistant capsule
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

Episodes classified by upper respiratory infections (otitis, tonsillitis, sinusitis, pharyngotonsillitis, nasopharyngitis) and lower respiratory tract (bronchitis, pneumonia).

Episodi infettivi classificati per apparato respiratorio superiore (otiti, tonsilliti, sinusiti, faringotonsilliti, rinofaringiti) e apparato respiratorio inferiore (bronchiti, polmoniti).

E.1.1.1

Medical condition in easily understood language

Respiratory tract infections.

Infezioni respiratorie ricorrenti.

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	PT
E.1.2	Classification code	10060693
E.1.2	Term	Respiratory tract infection bacterial
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Comparison, vs placebo, during 6 months of the infective episodes of the respiratory tract (number of days of illness) from the day of the first dose. Number of illness days recorded by the patient on a special diary.

Confronto, verso placebo, della durata complessiva a 6 mesi degli episodi infettivi suddivisi per ciclo di trattamento (numero giorni di affezione) a partire dal giorno della prima somministrazione, registrata dal paziente su apposito diario.

E.2.2

Secondary objectives of the trial

1) Assessment of BUCCALIN efficacy vs. placebo, comparing the number of infectious episodes of respiratory tract. 2) Assessment of BUCCALIN vs. placebo on the intensity of the signs and symptoms of infection. 3) Number of cases of patients with more than 1, 2, 3 or 4 acute episodes. 4) Frequency and severity of infection classified by: ear infections, tonsillitis, sinusitis, pharyngotonsillitis, nasopharyngitis and bronchitis, pneumonia. 5) Time of onset of first episode after the end of treatment. 6) Absence from work and work time lost. 7) Global effectiveness according to the investigator, evaluated on a scale of 5 points. 8) Wellness of patients evaluated with VAS after treatment. Safety and Tolerability: 1) Incidence of adverse events. 2) Global tolerability according to the investigator, evaluated on a scale of 4 points.

1) Valutazione dell'efficacia di BUCCALIN vs. placebo, confrontando il numero di episodi infettivi del tratto respiratorio. 2) Valutazione dell’efficacia di BUCCALIN vs. placebo per intensità dei segni e sintomi degli episodi infettivi. 3) Numero di casi di pazienti con più di 1, 2, 3 o 4 episodi acuti. 4) Frequenza e gravità degli episodi infettivi quali: otiti, tonsilliti, sinusiti, faringotonsilliti, rinofaringiti e bronchiti, polmoniti. 5) Tempo di insorgenza del primo episodio dopo il termine del trattamento. 6) Assenza dal lavoro e tempo di lavoro perso. 7) Efficacia globale secondo lo sperimentatore, valutata su scala di 5 punti. 8) Benessere del paziente valutato con VAS, dopo trattamento. Sicurezza e tollerabilità: 1) Incidenza degli eventi avversi. 2) Tollerabilità globale secondo lo sperimentatore, valutata su una scala di 4 punti

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1 Patients of both sexes, aged between 18 and 65 years, who have suffered, during the previous year, from 2 to 6 episodes of bacterial infections of the upper respiratory tract; 2 Absence of malformations and /or active clinically significant disease; 3 Patients able to understand and follow the requirements specified by investigator and in study protocol.

1. Pazienti di ambo i sessi, di età compresa tra 18 e 65 anni, con un numero di precedenti episodi di infezioni del tratto respiratorio (IRR) di sospetta origine batterica, compreso tra 2 e 6 nell’anno precedente. 2. Assenza di malformazioni e/o patologie in grado di influenzare la raccolta dei dati dello studio in atto. 3. Pazienti in grado di comprendere e seguire quanto richiesto dal protocollo di studio.

E.4

Principal exclusion criteria

1) During acute episodes (infectious and noninfectious) at randomization, at the expense of any equipment, requiring hospitalization and / or intensive care. 2) Gastroesophageal reflux 3) Carriers of autoimmune diseases. 4) Treatment with any of the products belonging to ATC gruop J06 (immune sera and immunoglobulins) or J07AX (immunostimulant) taken in the two weeks prior to recruitment. 5) Treatment in the two weeks prior to recruitment or suppository treatment needs for the entire duration of the study, including the period of follow-up with: ATC group J07AX (immunostimulants); ATC group L01 antineoplastic; drugs belonging to the ATC groups L03 and L04 as cytokines, interleukins, interferon, immunosuppressant; systemic corticosteroids. 6) History of allergy or intolerance to the investigational product and / or excipients. 7) Patients unable to linguistic or psychological reasons, to understand the information given to obtain the consent or refuse to give consent in writing. 8) Another clinical study in the previous month or during this study. 9) Women who are pregnant or breastfeeding.

1. Episodi acuti in corso (infettivi e non infettivi) in atto al momento della randomizzazione, a carico di qualsiasi apparato, che richiedano ospedalizzazione e/o terapia intensiva. 2. Reflusso gastroesofageo. 3. Portatori di malattie autoimmuni. 4. Trattamento con qualsiasi prodotto appartenente ai gruppi ATC J06 (sieri immuni ed immunoglobuline) o J07AX (immunostimolanti) nelle due settimane precedenti il reclutamento. 5. Trattamento nelle due settimane precedenti il reclutamento o supposta necessità di trattamento per l'intera durata dello studio, compreso il periodo di follow-up con: immunostimolanti appartenenti al gruppo ATC J07AX; antineoplastici appartenenti al gruppo ATC L01; farmaci appartenenti ai gruppi ATC L03 e L04 come citochine, interleuchine, interferone, immunosoppressori; corticosteroidi sistemici. 6. Storia di allergia o intolleranza ai prodotti in studio e/o agli eccipienti. 7. Pazienti impossibilitati, per motivi linguistici o psicologici, a comprendere le informazioni date per l'ottenimento del consenso o che rifiutino di dare il proprio consenso in forma scritta. 8. Altro studio clinico nel mese precedente o durante questo studio. 9. Donne in gravidanza o in allattamento.

E.5 End points

E.5.1

Primary end point(s)

Total duration of infection, expressed in days, along the 6 months after initiation of treatment. One episode will be considered ''new'' if it occurs at least 72 hours after the resolution of the previous episode.

Durata complessiva degli episodi infettivi, espressa in giorni, osservata nell'arco di 6 mesi dopo l'inizio del trattamento. Un episodio sarà considerato “nuovo“ se intercorrono almeno 72 ore, in completa assenza di sintomi, dalla risoluzione del precedente episodio.

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months

6 mesi

E.5.2

Secondary end point(s)

1. Evaluation after 6 months of BUCCALIN effect vs. placebo on the reduction of number of infection acute episodes; 2. Number of cases of patients with more than 1, 2, 3 or 4 acute episodes; 3. Frequency and severity, after 6 months, of the infections of the upper and lower respiratory tract; 4. Intensity of the following signs and symptoms: fever, dyspnea, cough, pain, malaise, 5. Onset time (days) of first episode after treatment; 6. Use of other drugs and/or use of clinical care; 7. Day of absence from work at 4 and 6 months; 8. Overall effectiveness evaluated by investigator, after 4 and 6 months, using a 5-score scale; 9. Well-being, assessed by patients by VAS scale, after 6 months. Tolerability secondary end-points: 1) Incidence of adverse events. 2) Global tolerability according to the investigator, evaluated on a scale of 4 points at the end of treatment (visit to the sixth month).

1. Valutazione a 4 e 6 mesi degli effetti, verso placebo, del trattamento con BUCCALIN sulla riduzione del numero complessivo di episodi infettivi. 2. Numero di casi di pazienti con più di 1, 2, 3 o 4 episodi acuti. 3. Frequenza e gravità a 6 mesi, degli episodi infettivi classificati per apparato respiratorio superiore (otiti, tonsilliti, sinusiti, faringotonsilliti, rinofaringiti) e apparato respiratorio inferiore (bronchiti, polmoniti). 4. Intensità dei seguenti segni e sintomi: febbre, dispnea, tosse, dolore, stato di malessere (VAS). 5. Tempo di insorgenza, espresso in giorni, del primo episodio dopo il termine del trattamento inteso come ultima dose assunta. 6. Consumo di farmaci, a 4 e 6 mesi, aggregati per classi terapeutiche (antibiotici, broncodilatatori, decongestionanti, antipiretici, ecc.) e del ricorso ad altri interventi assistenziali (visite del medico di medicina generale, visite specialistiche, ospedalizzazioni, ecc.). 7. Giorni di assenza dalla comunità (a 4 e 6 mesi). 8. Efficacia globale secondo lo sperimentatore, valutata su una scala di 5 punti, dopo 4 e 6 mesi dall’inizio del trattamento. 9. Benessere da parte dei pazienti valutato con VAS, durante i sei mesi antecedenti e dopo 4 e 6 mesi dall’inizio del trattamento. End points sulla tollerabilità: 1)Incidenza degli eventi avversi. 2) Tollerabilità globale secondo lo sperimentatore, valutata su una scala di 4 punti alla fine del trattamento (visita di fine studio).

E.5.2.1

Timepoint(s) of evaluation of this end point

6 months

6 mesi

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

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)

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

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

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

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:

180

F.1.3

Elderly (>=65 years)

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2012-03-19.

Yes

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

180

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)

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

2012-05-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-03-08

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

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