Clinical Trials Register

Summary
EudraCT Number:	2012-002430-36
Sponsor's Protocol Code Number:	AntibioTICS
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2012-11-12
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

Spain - AEMPS

A.2

EudraCT number

2012-002430-36

A.3

Full title of the trial

Multicentre, randomised, double-blinded, placebo-controlled trial of efficacy of amoxicilline/clavulanic acid in patients affected by tic disorder colonized by GAS. No-proft stidy.

Estudio multicentrico, randomizado, doble ciego, controlado con placebo, para valorar la eficacia de amoxicilina/clavulanico en pacientes con la enfermedad de tic causada por GAS. No Comercial.

A.3.1

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

Multicentre, randomised, double-blinded, placebo-controlled trial of efficacy of antibiotic therapy in patients affected by tic disorder and with group A streptococcal colonization, No-profit study.

Etudio multicentrico, randomizado, doble ciego, controlado con placebo, para valorar la terapia antibiotica en pacientes con la enfermedad de tic, causada por GAS (estreptococo grupo A). No comercial.

A.3.2

Name or abbreviated title of the trial where available

AntibioTICS

A.4.1

Sponsor's protocol code number

AntibioTICS

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	AZIENDA UNIVERSITARIA POLICLINICO UMBERTO I DI ROMA
B.1.3.4	Country	Italy
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	European Community
B.4.2	Country	European Union
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sapienza Universita' di Roma
B.5.2	Functional name of contact point	Dipartimento di Pediatria e NPI
B.5.3	Address:
B.5.3.1	Street Address	Via dei Sabelli 108
B.5.3.2	Town/ city	Roma
B.5.3.3	Post code	00185
B.5.3.4	Country	Italy
B.5.4	Telephone number	0644712288
B.5.5	Fax number	0644712229
B.5.6	E-mail	francesco.cardona@uniroma1.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	AUGMENTIN*BB SOSP FL 140ML C/C
D.2.1.1.2	Name of the Marketing Authorisation holder	GLAXOSMITHKLINE SpA
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	Powder for oral solution
D.3.4.1	Specific paediatric formulation	Yes
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.3.9.1	CAS number	26787-78-0
D.3.9.4	EV Substance Code	SUB05481MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
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	POTASSIUM CLAVULANATE
D.3.9.1	CAS number	61177-45-5
D.3.9.4	EV Substance Code	SUB12232MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	11.4
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	Powder and solvent for oral suspension
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

Chronic tic disorder

Enfermedad de Tic crónica

E.1.1.1

Medical condition in easily understood language

Tic disorder

Enfermedad de Tic

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Behaviours [F01]

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	10043834
E.1.2	Term	Tic disorder, unspecified
E.1.2	System Organ Class	100000004873

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Test the hypothesis that antibiotic treatment of GAS colonisation compared to placebo is associated with a larger reduction of tic and associated neuropsychiatric symptoms in the short-term (1 month) in patients with a tic disorder colonised by GAS.

Verificar la hipotesis de que el tratamiento antibiotico de la colonización por GAS comparado con placebo se asocia a una mayor reducción de los tics y de los sintomas neuropsiquiatricos a sociados a corto plazo( 1 mes) en pacientes con desordenes de tic colonizados por GAS.

E.2.2

Secondary objectives of the trial

Test the hypothesis that antibiotic treatment of GAS colonisation is superior to placebo in the long-term (1 year) reduction of tic and associated neuropsychiatric symptoms in patients with a tic disorder colonized by GAS. Investigate the influence of possible moderators on treatment outcome. Investigate the effects of antibiotic treatment on patient?s immune responses to GAS antigens.

comprobar la hipotesis de que el ttatamiento antibiotico de la colonización por GAS es superior al tratamiento placebo en la reducción de los tics y de los sintomas neuropsiquiatricos asociados a largo plazo ( 1 año). Investigar la influencia de posibles mediadores en el resultado. Investigar los efectos del tratamiento antibiotico de los pacientes en la respuesta inmune frente a antigenos GAS.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1 Participant and/or parents willing and able to give informed consent for participation in the study 2 Male or Female, aged 3-16. 3 Diagnosis of Tourette Syndrome or another chronic tic disorder according to DSM IV-TR criteria. 4 Evidence of GAS colonization at any visit of EMTICS Longitudinal Course Study. 5 Either no current psychotropic medication or on stable anti-tic medication for at least 2 months before the enrolment in the trial.6 Able (in the Investigators opinion) and willing to comply with all study requirements.

1 Participante y / o los padres que quieran y pueden dar su consentimiento informado para la participación en el estudio 2 Hombre o Mujer, edad 3-16. 3 Diagnóstico del Síndrome de Tourette o de otro trastorno de tic crónico según DSM IV-TR. 4 Evidencia de colonización GAS en cualquier visita de estudio EMTICS Curso Longitudinal. 5 Ausencia de medicación psicotropica actual o bien medicacion estable anti-tic durante al menos 2 meses antes de la inscripción en el estudio.6 Capacidad para participar (en opinión investigadores) y estár dispuesto a cumplir con todos los requisitos del estudio.

E.4

Principal exclusion criteria

The participant may not enter the study if ANY of the following apply: 1 Children and/or parents are unable to understand and comply with protocol 2 Any antibiotic treatment for any reason during the last month before enrolment in the trial. 3 Clinical manifestations of pharyngitis or other streptococcal infections at moment of enrolment in the trial. 4 Known or suspected hypersensitivity to penicillin or other -lactam antibacterials, a history of amoxicillin-clavulanate-associated cholestatic jaundice or hepatic dysfunction. 5 Known and/or suspected renal or hepatic impairment (due to the potential for drug-related toxicity in patients with such a condition). 6 Scheduled elective surgery or other procedures requiring general anaesthesia during the study. 7 Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant ability to participate in the study. 8 Participants who have participated in another research study involving an investigational product in the past 12 weeks

Los participantes no podrán participar en el estudio si presenta CUALQUIERA de las siguientes condiciones: 1 El niño y / o los padres no son capaces de entender y cumplir con el protocolo. 2 Cualquier tratamiento con antibióticos por cualquier motivo durante el mes anterior al estudio. 3 signos clínicos de la faringitis o infección estreptocócica otro en el momento de entrar en el estudio. 4 Conocimiento o sospecha de hipersensibilidad a la penicilina u otros antibióticos beta-lactámicos, antecedentes de ictericia colestásica o insuficiencia hepática asociada con el consumo de amoxicilina / ácido clavulánico. 5 Insuficiencia renal o hepática conocida y / o sospechosos (debido al potencial de toxicidad relacionada con antibioticos). 6 cirugías u otros procedimientos que requieran anestesia general durante el estudio. 7 Cualquier otra enfermedad o trastorno significativo que, de acuerdo con el investigador, puede poner a los pacientes en riesgo debido a la participación en el estudio y influir en el resultado del estudio o la capacidad del paciente para participar en el estudio. 8 Los participantes que hayan participado en otros estudios de investigación con un estudio de drogas en las últimas 12 semanas.

E.5 End points

E.5.1

Primary end point(s)

Yale Global Tic Severity Scale (YGTSS) Score

Escala de severidad de tic de Yale Global(YGTSS)

E.5.1.1

Timepoint(s) of evaluation of this end point

1 month

1 mes

E.5.2

Secondary end point(s)

1) Premonitory Urge for Tics Scale (PUTS) 2) Children?s Yale Brown Obsessive-Compulsive Scale (CYBOCS) 3) Symptoms of autism spectrum disorders, ADHD, and internalising and externalising psychopathology a. Social Communication Questionnaire (SCQ). b. Swanson, Nolan, and Pelham, version IV (SNAP-IV) rating scale. c. Strengths and Difficulties Questionnaire (SDQ). 4) Prenatal and perinatal adversities as assessed by parental self-report. 5) Psychosocial stress as measured using the Perceived Stress Scale (PSS), and the PSS-short version. 6) Cortisol levels in hair. 7) Microbiological typing of bacterial GAS population. 8) Anti-Streptococcal Immune Response.

1) urgencia premonitoria para escala de tics (PUTS) 2) Escala obsesiva compulsiva de la children´s Yale Brown (CYBOCS) 3) Espectro de desordenes en sintomas de autismo ADHD y internalización y externalización psicopatica a.Cuestionario de comunicación social (SCQ). b. Indice de escala Swanson, Nolan, and Pelham, version IV (SNAP-IV) . c.Cuestionario de puntos fuertes (SDQ). 4) Antecedentes prenatales y perinatales por informes propios de los padres. 5) Estres psicosocial como medida usando la escala de Estrespercividad (PSS) 6) niveles de cortisol en el pelo 7) Clasificación microbiologica del la población bacteriana GAS. 8) Respuesta immune anti-Streptococcica.

E.5.2.1

Timepoint(s) of evaluation of this end point

12 months

12 meses

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

E.6.5

Efficacy

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

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

Yes

E.8.4

The trial involves multiple sites in the 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

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

''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

Yes

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

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

Yes

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

F.4.2.2

In the whole clinical trial

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)

Study medication will not be continued beyond the trial period. Participants will transfer to normal care.

Este medicamento proporcionado por el estudio no se prolongará más allá del período del ensayo. Los participantes volveran a un sistema normal de atención y tratamiento..

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

2013-03-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-02-05

P. End of Trial
P.	End of Trial Status	Ongoing

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