Clinical Trials Register

Summary
EudraCT Number:	2012-005807-41
Sponsor's Protocol Code Number:	PRE-EMPTIVE
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2013-03-04
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2012-005807-41

A.3

Full title of the trial

RANDOMIZED CLINICAL TRIAL, PLACEBO-CONTROLLED, SPLIT-MOUTH, A DOUBLE-BLIND, FOR THE EVALUATION OF THE EFFECTIVENESS OF PRE-emptive ANALGESIA BY ADMINISTRATION OF PARACETAMOL 500MG + codeine 30mg, FOR THE CONTROL OF POSTOPERATIVE ACUTE PAIN in the extraction of IMPACTED THIRD MOLAR MANDIBULAR

TRIAL CLINICO RANDOMIZZATO, PLACEBO-CONTROLLATO, SPLIT-MOUTH, A DOPPIO CIECO, PER LA VALUTAZIONE DELL’EFFICACIA DELLA PRE-EMPTIVE ANALGESIA MEDIANTE SOMMINISTRAZIONE PER OS DI PARACETAMOLO 500MG + CODEINA 30MG, SUL CONTROLLO DEL DOLORE ACUTO POST-OPERATORIO NELL’ESTRAZIONE DEL TERZO MOLARE MANDIBOLARE INCLUSO

A.3.1

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

EVALUATION OF THE EFFECTIVENESS OF PRE-emptive ANALGESIA BY ADMINISTRATION OF PARACETAMOL 500MG + codeine 30mg, FOR THE CONTROL OF POSTOPERATIVE ACUTE PAIN in the extraction of IMPACTED THIRD MOLAR MANDIBULAR

VALUTAZIONE DELL’EFFICACIA DELLA PRE-EMPTIVE ANALGESIA MEDIANTE SOMMINISTRAZIONE PER OS DI PARACETAMOLO 500MG + CODEINA 30MG, SUL CONTROLLO DEL DOLORE ACUTO POST-OPERATORIO NELL’ESTRAZIONE DEL TERZO MOLARE MANDIBOLARE INCLUSO.

A.3.2

Name or abbreviated title of the trial where available

PRE-EMPTIVE ANALGESIA

A.4.1

Sponsor's protocol code number

PRE-EMPTIVE

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	"Sapienza" University of Rome
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	"SAPIENZA" UNIVERSITY OF ROME
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	"SAPIENZA" UNIVERSITY OF ROME
B.5.2	Functional name of contact point	DEPARTMENT OF ORAL AND MAXILLO FACI
B.5.3	Address:
B.5.3.1	Street Address	VIA CASERTA, 6
B.5.3.2	Town/ city	ROME
B.5.3.3	Post code	00161
B.5.3.4	Country	Italy
B.5.4	Telephone number	00390649976651
B.5.5	Fax number	00390644230811
B.5.6	E-mail	susanna.annibali@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	COEFFERALGAN
D.2.1.1.2	Name of the Marketing Authorisation holder	BRISTOL-MYERS SQUIBB Srl
D.2.1.2	Country which granted the Marketing Authorisation	France
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	COEFFERALGAN
D.3.4	Pharmaceutical form	Capsule, hard
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	CODEINE
D.3.9.1	CAS number	52-28-8
D.3.9.3	Other descriptive name	CODEINE PHOSPHATE
D.3.9.4	EV Substance Code	SUB13427MIG
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	30
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PARACETAMOL
D.3.9.1	CAS number	103-902
D.3.9.3	Other descriptive name	ACETAMINOFEN
D.3.9.4	EV Substance Code	SUB09611MIG
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	500
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	Capsule, hard
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

POST-OPERATIVE ACUTE PAIN (DAPO)

DOLORE ACUTO POST-OPERATORIO

E.1.1.1

Medical condition in easily understood language

POST-OPERATIVE ACUTE PAIN

DOLORE ACUTO POST-OPERATORIO

E.1.1.2

Therapeutic area

Diseases [C] - Mouth and tooth diseases [C07]

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	10031009
E.1.2	Term	Oral pain
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

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	10030973
E.1.2	Term	Oral discomfort
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

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 aim of this study was to evaluate the analgesic effect of paracetamol + codeine (P + C) in patients undergoing surgical extraction of mandibular third molars included.

Scopo dello studio è valutare l’effetto analgesico della somministrazione preventiva di paracetamolo+codeina (P+C) nei pazienti sottoposti ad estrazione chirurgica dei terzi molari mandibolari inclusi.

E.2.2

Secondary objectives of the trial

- Objective 1: To test the effect of preventive administration of P + C on the intensity of acute post-operative pain (DAPO), also taking into account patient characteristics (age, sex) and surgery (side operated first , duration and degree of difficulty of the operation);
- Objective 2: To test the effect of preventive administration of P + C on postoperative consumption of the same drug (measured in number of tablets), also taking into account patient characteristics (age, sex) and surgery (side work first, duration and degree of difficulty of the operation);
- Objective 3: To evaluate the effect of time on the variation of the intensity of pain during the post-operative (curve of pain) and the number of analgesic tablets support (rescue therapy) taken by patients;
- Objective 4: To assess the effect of rescue therapy on the time variation of the degree of pain.

-Obiettivo 1: verificare l’effetto della somministrazione preventiva di P+C sull’intensità del dolore acuto post-operatorio (DAPO), tenendo conto anche delle caratteristiche dei pazienti (età, sesso) e dell’intervento chirurgico (lato operato per primo, durata e grado di difficoltà dell’intervento);
-Obiettivo 2: verificare l’effetto della somministrazione preventiva di P+C sul consumo post-operatorio dello stesso farmaco (valutato in numero di compresse), tenendo conto anche delle caratteristiche dei pazienti (età, sesso) e dell’intervento chirurgico (lato operato per primo, durata e grado di difficoltà dell’intervento);
-Obiettivo 3: valutare l’effetto del tempo sulla variazione dell’intensità di dolore durante la fase post-operatoria (curva del dolore) e sul numero di compresse analgesiche di supporto (rescue therapy) assunte dai pazienti;
-Obiettivo 4: valutare l’effetto della rescue therapy sulla variazione nel tempo del grado di dolore.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

males and females aged between 18 and 40 years, absence of systemic disease (ASA class I), non-smoking or smoking <10 cigarettes / day; plaque index and bleeding less than 25%, indicating to extract both lower wisdom teeth inclusion in partial or total bilateral bone (osteotomy applicant), similar in depth, inclination and position, no medication in the 10 days prior to the extraction, presence in the arch of the first and second molars, absence of pain and associated osteolytic disease.

soggetti maschi e femmine di età compresa tra i 18 e 40 anni; assenza di patologie sistemiche (classe ASA I); non fumatori o fumatori <10 sigarette/die; indice di placca e di sanguinamento inferiore al 25%; indicazione a estrarre entrambi i denti del giudizio inferiori in inclusione ossea parziale o totale bilaterale (richiedente osteotomia), simili per profondità, inclinazione e posizione; nessuna assunzione di farmaci nei 10 giorni precedenti l’estrazione; presenza in arcata del primo e del secondo molare; assenza di sintomatologia dolorosa e patologie osteolitiche associate.

E.4

Principal exclusion criteria

PREGNANT WOMEN AND / OR BREASTFEEDING WOMEN
SUBJECTS < 18 YEARS-OLD

DONNE IN GRAVIDANZA E/O E IN ALLATTAMENTO; SOGGETTI MINORENNI

E.5 End points

E.5.1

Primary end point(s)

REGISTRATION pain intensity at fixed times (8:00-13:00-18:00-23:00), so as to obtain the "curve of pain"; For the evaluation of the degree of pain, will be used for both diaries a numerical scale (Numeral Rating Scale-11, NRS-11), presented graphically as a vertical column of 100 mm oriented from bottom to top, divided into 11 equal squares with numbers from 0 to 10. The two ends of the scale were defined as "no pain" to "worst pain imaginable."

REGISTRAZIONE DELl’intensità del dolore in corrispondenza di orari prestabiliti (8:00-13:00-18:00-23:00), in modo da ottenere la “curva del dolore”; Per la valutazione del grado di dolore, verrà utilizzata per entrambi i diari una scala numerica (Numeral Rating Scale-11, NRS-11), presentata graficamente come una colonna verticale di 100 mm orientata dal basso verso l’alto, divisa in 11 caselle uguali con numeri da 0 a 10. Le due estremità della scala sono state definite da “nessun dolore” fino a “massimo dolore immaginabile”.

E.5.1.1

Timepoint(s) of evaluation of this end point

7 DAYS

7 GIORNI

E.5.2

Secondary end point(s)

intake of a possible compressed support (rescue therapy) and the intensity of the pain associated.

assunzione di un’eventuale compressa di supporto (rescue therapy) e l’intensità del dolore associato.

E.5.2.1

Timepoint(s) of evaluation of this end point

7 DAYS

7 GIORNI

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

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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

Yes

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

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.1.1.1

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:

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

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.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

2013-04-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-02-21

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

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