Clinical Trials Register

Summary
EudraCT Number:	2004-001201-10
Sponsor's Protocol Code Number:	FEN-PPA-401
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-03-20
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

Spain - AEMPS

A.2

EudraCT number

2004-001201-10

A.3

Full title of the trial

Comparison of transdermal fentanyl PCA and IV morphine PCA in the management of post-operative pain control.

Comparación de fentanilo transdérmico PCA y morfina intravenosa PCA para el control del dolor postoperatorio

A.3.1

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

Comparación de fentanilo transdérmico y morfina intravenosa en analgesia controlada por el paciente para el control del dolor postoperatorio.

A.3.2

Name or abbreviated title of the trial where available

Euro-Trans study

Euro-Trans

A.4.1

Sponsor's protocol code number

FEN-PPA-401

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	Janssen-Cilag EMEA Medical Affairs
B.1.3.4	Country	Belgium
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	Janssen-Cilag EMEA Medical Affairs
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen-Cilag EMEA Medical Affairs
B.5.2	Functional name of contact point	Sandra Waechter
B.5.3	Address:
B.5.3.1	Street Address	Turnshoutseweg 30
B.5.3.2	Town/ city	Beerse
B.5.3.3	Post code	B-2340
B.5.3.4	Country	Belgium
B.5.4	Telephone number	41417673432
B.5.5	Fax number	41417673400
B.5.6	E-mail	swaechte@jacch.jnj.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	FENTANYL
D.3.2	Product code	R004263
D.3.4	Pharmaceutical form	Transdermal patch
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Transdermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	1443-54-5
D.3.9.3	Other descriptive name	FENTANYL HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB21234
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	40 to 25
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.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.2.5	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	MORPHINE
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous bolus use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	57-27-2
D.3.9.3	Other descriptive name	MORPHINE
D.3.9.4	EV Substance Code	SUB03332MIG
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	240
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

post-operative pain control

Control del dolor postoperatorio

E.1.1.1

Medical condition in easily understood language

Control del dolor postoperatorio

E.1.1.2

Therapeutic area

Diseases [C] - Symptoms and general pathology [C23]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Aim of this study
This study will evaluate the clinical use, safety and and ease of care of a Transdermal PCA system and morphine IV PCA for management of moderate to severe acute pain in post?operative subjects who have undergone elective major abdominal or orthopaedic surgery. Subjects are expected to require parenteral opioids for at least 24 hours post-operatively. As much as possible, management of all aspects of the care for the subject during hospital stay not directly related to analgesic management of post-operative pain will be in accordance with each study center's standard clinical practice.
The primary objective of this study is to evaluate the clinical use of Transdermal PCA treatment and morphine IV PCA treatment for the management of moderate to severe post?operative pain in subjects who have undergone an elective major abdominal or orthopaedic procedure.

E.2.2

Secondary objectives of the trial

· To assess pain control in both treatment groups, including the Subject?s and Physician?s Global Treatment Assessments,
· To compare the Safety of Transdermal PCA system for pain management in this surgical population with the Safety of morphine IV PCA,
· To explorate the impact on care procedures of the Transdermal PCA system and morphine IV PCA device, by means of validated Ease of Care Questionnaires, related to the subject, nursing staff and physical therapists.
· To compare technical issues with both systems.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects must satisfy the following criteria to be enrolled in the study:
1. Adult, age 18 or older, male or female;
2. American Society of Anesthesiology (ASA) pre-operative physical status I, II, or III (Attachment 2);
3. If the subject is female and of childbearing potential, she must have a negative pregnancy test after hospital admission, unless patient is undergoing hysterectomy;
4. Subjects, after an elective major abdominal or orthopaedic procedure, who are expected to have moderate or severe pain requiring parenteral opioids for at least 24 hours after surgery;
5. Subjects who are capable of understanding and cooperating with the requirements of the study and operating the Transdermal PCA system or the IV PCA device;
6. Subjects who have signed and dated an informed consent to participate in the study during the pre-operative assessment;
7. Subjects who have been admitted to the recovery room after general anesthesia, spinal anesthetic of < 4 hours duration of action or epidural anesthesia after an elective major abdominal or orthopaedic procedure and who expectedly suffer from moderate to severe pain and will require post-operative analgesia for at least 24 hours. Subjects with epidural or regional anesthesia will only be included if the provided analgesia was short lasting and was only given for the period of surgery and not for the period in the recovery room. When entering the recovery room, subjects with epidural or regional anesthesia must still qualify for needing IV PCA analgesia according to the local hospital standards;
8. Subjects who are alert and breathing spontaneously for at least 30 minutes in the waking room; respiratory rate 10 to 24 breaths per minute; SpO2 ³90% (with or without supplemental oxygen), subjects must be able to answer questions and follow commands;
9. Subjects with a pain score less than or equal to 4 out of 10 on a Numerical Rating Scale (NRS) after titration to comfort with IV morphine. In case of abdominal surgery, this should be measured five minutes after deep breathing and coughing;
10. Subjects who are expected to remain hospitalized for at least 24 hours post-operatively.

E.4

Principal exclusion criteria

Potential subjects who meet any of the following criteria will be excluded from participating in the study:
1. Subjects with a history of allergy or hypersensitivity to fentanyl and/or morphine and/or an allergy/hypersensitivity to skin adhesives and/or cetylpyridinium chloride;
2. Subjects who are known or suspected to be strong opioid dependent, or who have a too high a need for strong opioids;
3. Subjects with a history of psychological opioid dependence before the start of the study, defined as meeting any of the criteria for substance dependence specified in Attachment 3;
4. Subjects who are known or suspected to have abused any drug substance or alcohol (see Attachment 4);
5. Subjects with chronic pain disorder (DSM-IV: F45.4);
6. Subjects with active systemic skin disease or active local skin disease that precludes Transdermal PCA system application;
7. Subjects known to have any of the following:
· severe chronic obstructive respiratory symptoms,
· susceptibility to present respiratory depression (possible synergistic effect associated with CNS drugs);
· subjects with renal dysfunction;
· subjects who have a coexisting medical condition, (possibly with chronic pain of another organ) that is likely to interfere with study procedures.
Remark:
- use of muscle relaxants is allowed;
- use of anti-depressants/anxiolytics is allowed provided that they were taken for the same indication before surgery;
8. Women who are pregnant, breast feeding, or planning to breast feed within 7 days of last dose of study drug;
9. Subjects who have taken any investigational drug or used an experimental medical device within 30 days before the start of the study or are currently enrolled in another investigational drug study;
10. Subjects who have previously enrolled in a Transdermal PCA study;
11. Subjects who have received peri-operative administration of opioids other than morphine, fentanyl, sufentanil, alfentanil or remifentanil.
Exception: If there are no medical contraindications, one dose of meperidine, up to 50 mg IV, is allowed within 30 minutes of arrival in the waking room for shivering;
12. Subjects who need very high doses of opioids to control their pain (more than 40 mg morphine/h) or more than 6 hours have elapsed since the subject arrived in the waking room;
13. Subjects whose post-operative pain would normally be managed with oral or non-opioid analgesia during the first 24 hours;
14. Subjects who are being treated in the intensive care unit;
15. Subjects who will probably require additional surgical procedures within 72 hours;
16. Subjects who are intubated or have a laryngeal mask airway (LMA) at the time of final screening assessments;
17. Subjects who are employees of the investigator or the institution who have direct involvement in the study or other trials under the direction of the investigator.

E.5 End points

E.5.1

Primary end point(s)

Primary end point: The study is designed to demonstrate non-inferiority of Transdermal PCA versus morphine IV PCA treatment in subject?s global assessment of method of pain control during the first 24 hours post-surgery

E.5.1.1

Timepoint(s) of evaluation of this end point

A las 24 horas tras cirugía mayor abdominal u ortopédica

E.5.2

Secondary end point(s)

Objetivos secundarios:
? Evaluar el control del dolor en los dos grupos de tratamiento, incluyendo las Evaluaciones Globales del Tratamiento Realizadas por el Paciente y el Médico.
? Comparar la Seguridad del dispositivo de PCA Transdérmica frente a la Seguridad de la PCA-IV con morfina en el manejo del dolor de esta población quirúrgica.
? Investigar la influencia del dispositivo de PCA Transdérmica frente a PCA-IV con morfina en términos de atención al paciente, a través de los Cuestionarios sobre Facilidad de Prestación de Cuidados Médicos validados que serán cumplimentados por los pacientes, el personal de enfermería y los fisioterapeutas.
? Comparar los aspectos técnicos de ambos dispositivos.

E.5.2.1

Timepoint(s) of evaluation of this end point

A las 24 horas tras cirugía mayor abdominal u ortopédica

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

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)

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

Yes

E.8.1.3

Single blind

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

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

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

(Please, refers to protocol appropiate section)

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