Clinical Trials Register

Summary
EudraCT Number:	2012-004796-39
Sponsor's Protocol Code Number:	PT-SM-14-OA
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2013-04-23
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2012-004796-39

A.3

Full title of the trial

A Comparative Study of Oxycodone/Naloxone versus Codeine/Paracetamol in the Treatment of Moderate to Severe Chronic Knee and/or hip Pain Due to Osteoarthritis

Studio comparativo tra le due associazioni farmacologiche ossicodone/naloxone e codeina/paracetamolo nel trattamento del dolore cronico moderato-severo da osteoartrosi del ginocchio e/o dell’anca

A.3.1

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

Study to compare Oxycodone/Naloxone to Codeine/Paracetamol in the Treatment of Knee and/or hip Pain Due to Osteoarthritis

Studio per il confromto tra ossicodone/naloxone e codeina/paracetamolo nel trattamento del dolore del ginocchio e/o dell’anca da osteoartrosi

A.3.2

Name or abbreviated title of the trial where available

PT-SM-14-OA

A.4.1

Sponsor's protocol code number

PT-SM-14-OA

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	Fondazione IRCCS Policlinico San Matteo
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	Fondazione IRCCS Policlinico San Matteo
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	Fondazione IRCCS Policlinico San Matteo
B.5.2	Functional name of contact point	Struttura di terapia del dolore
B.5.3	Address:
B.5.3.1	Street Address	P.le Golgi 19
B.5.3.2	Town/ city	Pavia
B.5.3.3	Post code	27100
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390382502627
B.5.5	Fax number	+390382502226
B.5.6	E-mail	m.allegri@smatteo.pv.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	Targin
D.2.1.1.2	Name of the Marketing Authorisation holder	Mundipharma Pharmaceuticals 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.3.1	Product name	Targin
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Prolonged-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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.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	CO-EFFERALGAN®
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb S.a.r.l.
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.3.1	Product name	Co-efferalgan
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Moderate to Severe Chronic Knee and/or hip Pain Due to Osteoarthritis

Dolore cronico moderato-severo da osteoartrosi del ginocchio e/o dell’anca

E.1.1.1

Medical condition in easily understood language

Moderate to Severe Chronic Knee and/or hip Pain Due to Osteoarthritis

Dolore cronico moderato-severo da osteoartrosi del ginocchio e/o dell’anca

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

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	10023476
E.1.2	Term	Knee osteoarthritis
E.1.2	System Organ Class	100000004859

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	10020108
E.1.2	Term	Hips osteoarthritis
E.1.2	System Organ Class	100000004859

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluate the differences in terms of efficacy and tolerability between two pharmacological protocols in patients with chronic pain from osteoarthritis

Valutare le differenze in termini di efficacia e tollerabilità tra due protocolli farmacologici nei pazienti affetti da dolore cronico da osteoartrosi.

E.2.2

Secondary objectives of the trial

- Evaluation of the differences, between the two pharmacological protocols, in terms of quality of life, by means of the SF-12.

- Evaluation of the differences, between the two pharmacological protocols, in scores obtained in the WOMAC physical function and stiffness subscales.

Valutare le differenze, tra i due protocolli farmacologici, in termini di qualità di vita, mediante il questionario SF-12.

Valutazione delle differenze, tra i due protocolli farmacologici, nei punteggi ottenuti nelle due sezioni, funzionalità e rigidità, del questionario WOMAC.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Male or female subjects older than 60 years old.
• Subjects with a clinical diagnosis of degenerative or primary OA with moderate to severe chronic pain (NRS>4) that require around-the-clock opioid therapy. Subjects will identify the most painful joint (hip or knee) for documentation of OA. Pain measurement will be done at this joint only.
• Subjects willing and able to participate in all aspects of the core study, including use of oral medication, completion of subjective evaluations, attending scheduled clinic visits, completing telephone contacts, and compliance with protocol requirements as evidenced by providing written, informed consent.
• Subjects in which the pre-study, non-opioid analgesics, and all other concomitant medications, including those medications for the treatment of depression are anticipated to remain stable throughout the treatment phase of the study.

• Soggetti maschi e femmine di età superiore ai 60 anni
• Soggetti con diagnosi di osteoartrite degenerativa o primaria, e che riferiscano un dolore moderato-severo (NRS>4) tale da richiedere una terapia oppioide. La sintomatologia dolorosa dovrà riguardare ginocchio e/o anca, mono o bilateralmente. Le rilevazioni dell’intensità del dolore saranno mirate al solo distretto anatomico interessato dalla sintomatologia algica al momento dell’arruolamento. Soggetti per i quali non sia stata posta indicazione chirurgica.
• Soggetti in grado di comprendere le finalità dello studio e che abbiano firmato un consenso informato scritto.
• Soggetti in grado di assumere correttamente le terapie prescritte, comprendere e compilare i questionari e le schede di valutazione.
• Soggetti le cui terapie farmacologiche non-oppioidi antecedenti l’arruolamento siano stabili.

E.4

Principal exclusion criteria

• Any history of hypersensitivity to oxycodone, naloxone, codeine, ibuprofen, or related products and ingredients.
• Any contraindication to oxycodone, naloxone, codeine, paracetamol or ibuprofen.
• Subjects with evidence of significant structural abnormalities of the GI tract (e.g., bowel obstruction, strictures) or any diseases/conditions that affect bowel transit (e.g., ileus, hypothyroidism).
• Subjects with cancer associated pain.
• Subjects with secondary osteoarthritis (e.g. fracture, septic, acromegaly etc.).
• Active alcohol or drug abuse and/or history of opioid abuse.
• Subjects with Rheumatoid Arthritis.
• Subjects with evidence of clinically unstable disease
• Subjects with active or history of epilepsy
• Subjects receiving hypnotics or other CNS depressants that, in the in Ivestigator's opinion, may pose a risk of additional CNS depression with opioid study medication
• Subjects with evidence of impaired liver/kidney function upon entry into the study defined as: Aspartate aminotransferase, alanine aminotransferase (AST, ALT) levels >3 times the upper limit of normal; Gamma glutamyl transpeptidase (GGT) ≥5 times the upper limit of normal; Total bilirubin level outside of the reference range (unless the value is associated with pre documented Gilbert's Syndrome); cholinesterase <2000 UI; INR>2; Creatinine clearance < 40 ml/min.
• Subjects with a history of depression or other psychiatric disorder that in the opinion of the investigator is significant enough to exclude the subject from the study.
• Mental impaired patients.

• Storia di ipersensibilità a ossicodone, naloxone, codeina, paracetamolo, ibuprofene, e agli eccipienti contenuti nelle formulazioni oggetto di studio.
• Controindicazioni all’uso di ossicodone, naloxone, codeina, paracetamolo o ibuprofene.
• Soggetti con alterazioni strutturali note a carico del tratto gastroenterico (es: sindromi aderenziali, stenosi cicatriziali) o pazienti affetti da patologie note a carico del tratto gastroenterico tali da modificare ed interferire con il transito intestinale.
• Soggetti affetti da patologia neoplastica.
• Soggetti con osteoartrite secondaria (es: fratture, acromegalia).
• Storia di abuso di alcol e/o droghe.
• Storia di abuso di sostanze oppioidi.
• Pazienti affetti da artrite reumatoide.
• Pazienti con evidenza di patologie mediche o chirurgiche non stabili.
• Pazienti con storia pregressa o attuale di epilessia.
• Pazienti in trattamento con farmaci ad azione depressiva sul Sistema Nervoso Centrale che a giudizio dello sperimentatore possano risultare in effetti additivi con i farmaci oggetto di studio.
• Soggetti con insufficienza renale e/o epatica severa. Per insufficienza renale severa si considererà una clearance della creatinina < 40 ml/min. Per insufficienza epatica severa si considererà un aumento dei valori delle transaminasi (ALT, AST) di 3 volte superiore ai limiti di normalità, un aumento del valore di GGT di 5 volte superiore ai limiti di normalità, valori di bilirubinemia superiori ai limiti di normalità (ad eccezione dei pazienti affetti da Sindrome di Gilbert), colinesterasi <2000UI, INR>2.
• Soggetti con storia di depressione o altra patologia psichiatrica che, a giudizio dello sperimentatore possano interferire con la partecipazione allo studio.
• Soggetti con alterazioni cognitive e/o ritardo mentale.

E.5 End points

E.5.1

Primary end point(s)

Evaluate the differences in terms of efficacy and tolerability between two pharmacological protocols in patients with chronic pain from osteoarthritis.

Valutare le differenze in termini di efficacia e tollerabilità tra due protocolli farmacologici nei pazienti affetti da dolore cronico da osteoartrosi.

E.5.1.1

Timepoint(s) of evaluation of this end point

15 days

15 giorni

E.5.2

Secondary end point(s)

Evaluation of the differences, between the two pharmacological protocols, in terms of quality of life, by means of the SF-12.

Evaluation of the differences, between the two pharmacological protocols, in scores obtained in the WOMAC physical function and stiffness subscales.

E.5.2.1

Timepoint(s) of evaluation of this end point

30 and 90 days

30 e 90 giorni

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

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

Yes

E.8.1.4

Double blind

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)

Yes

E.8.2.2

Placebo

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

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.1.1.1

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)

Yes

F.1.3.1

Number of subjects for this age range:

100

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

182

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)

Subjects will continue the treatment

I soggetti proseguiranno con il trattamento in atto

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

2013-04-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-12-17

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2015-11-03

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