Clinical Trials Register

Summary
EudraCT Number:	2012-004585-18
Sponsor's Protocol Code Number:	KKS-190
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-12-07
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

Germany - BfArM

A.2

EudraCT number

2012-004585-18

A.3

Full title of the trial

Perioperative administration of Tapentadol – tolerance, safety and effects on postoperative rehabilitation and quality of life.
Randomized, controlled study to compare the analgesic therapy with tapentadol compared to pure opioid receptor agonists

Perioperativer Einsatz von Tapentadol – Verträglichkeit, Sicherheit und Auswirkungen auf die postoperative Wiederherstellung und Lebensqualität.
Randomisierte , kontrollierte Studie zum Vergleich der Schmerztherapie mit Tapentadol gegenüber reinen Opioidrezeptoragonisten

A.3.1

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

Standard-armed controlled study to assess the impact of tapentadol administration after hysterectomy, prostatektomy or nephrektomie on quality of life and pain management as well as on safety and tolerability in comparison to a conventional pain therapy with morphine using a historical control group.

Standardarm kontrollierte Studie, um die Auswirkungen von Tapentadolgabe nach Hysterektomie, Prostatektomy oder Nephrektomie bei Männern auf die Lebensqualität und Schmerztherapie sowie die Sicherheit und Verträglichkeit zu beurteilen, im Vergleich zu einer konventionellen Schmerztherapie mit Morphin.

A.3.2

Name or abbreviated title of the trial where available

PATENT - Perioperative Administration of TapENTadol

PATENT - PerioperATiver Einsatz von TapeNTadol

A.4.1

Sponsor's protocol code number

KKS-190

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	Philipps-Universität Marburg
B.1.3.4	Country	Germany
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	Grünenthal
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Philipps-Universität Marburg
B.5.2	Functional name of contact point	KKS Marburg
B.5.3	Address:
B.5.3.1	Street Address	Karl-von-Frisch-Straße 4
B.5.3.2	Town/ city	Marburg
B.5.3.3	Post code	35043
B.5.3.4	Country	Germany
B.5.4	Telephone number	0049642128 66509
B.5.5	Fax number	0049642128 66517
B.5.6	E-mail	info@kks.uni-marburg.de

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	Palexia retard Retardtabletten (Wirkstoff: Tapentadol)
D.2.1.1.2	Name of the Marketing Authorisation holder	Grünenthal Deutschland
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Palexia® retard Retardtabletten
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	175591-23-8
D.3.9.2	Current sponsor code	KKS-190
D.3.9.3	Other descriptive name	TAPENTADOL
D.3.9.4	EV Substance Code	SUB31821
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	50
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	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	Palexia 50 mg film-coated tablets (Wirkstoff: Tapentadol) -Pharmakologisch gleiches Produkt für Deutschland ist Yantil(Grünenthal), dieses ist zugelassen aber nicht auf dem Markt erhältlich.
D.2.1.1.2	Name of the Marketing Authorisation holder	Grunenthal Ltd
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Palexia 50 mg film-coated tablets
D.3.4	Pharmaceutical form	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.3.9.1	CAS number	175591-23-8
D.3.9.2	Current sponsor code	KKS 190
D.3.9.3	Other descriptive name	TAPENTADOL
D.3.9.4	EV Substance Code	SUB31821
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
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)	Yes
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: 3
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	Palexia retard (Wirkstoff: Tapentadol)
D.2.1.1.2	Name of the Marketing Authorisation holder	Grünenthal
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Palexia® retard Retardtabletten
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	175591-23-8
D.3.9.2	Current sponsor code	KKS-190
D.3.9.3	Other descriptive name	TAPENTADOL
D.3.9.4	EV Substance Code	SUB31821
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	100
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

Hysterectomy with ASA 1-3, Prostatectomy with ASA 1-3, Nephrectomy with ASA 1-3

Hysterektomie mit ASA 1-3, Prostatektomie mit ASA 1-3, Nephrektomie mit ASA 1-3

E.1.1.1

Medical condition in easily understood language

Hysterectomy (no Emergency) Prostatectomy (no Emergency) , Nephrectomy (no Emergency)

Gebärmutterentfernung (kein Notfall), Prostataentfernung (kein Notfall), Entfernung einer Niere (kein Notfall)

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04]

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	10021151
E.1.2	Term	Hysterectomy
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

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	10029116
E.1.2	Term	Nephrectomy
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

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	10061916
E.1.2	Term	Prostatectomy
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Simplified PONV Impact Scale Score [Wengritzky 2012]

E.2.2

Secondary objectives of the trial

• SDS scores for opioid-associated adverse events in the dimensions severity, frequency, and subjective burden [Apfelbaum 2004]
• HORQ-scores for satisfaction and activity level after description in [Apfelbaum 2004]
• Total score of PPP33 questionnaire [Eberhart 2004]
• Total score of PPP16 FT-questionnaire [Eberhart 2008]
• SF-12 questionnaire
• analgesic consumption
• measuring pain (numerical rating scale of 0 to 10)
Additional outcomes:
• Duration of opioid pain therapy
• need for anesthetic drugs (for BIS-guided anesthesia with target: BIS Index: 40-60)

• SDS-Scores für opioidassoziierte Nebenwirkungen in den Dimensionen Schwere, Häufigkeit, subjektive Belastung [Apfelbaum 2004]
• HORQ-Scores für Zufriedenheit und Aktivitätsniveau nach der Be-schreibung in [Apfelbaum 2004]
• Summenscore des PPP33-Fragebogens [Eberhart 2004]
• Summenscore des PPP16-FT-Fragebogens [Eberhart 2008]
• SF-12-Fragebogen
• Schmerzmittelverbrauch
• Schmerzmessung (numerische Ratingskala von 0 bis 10)
• Dauer der Opioidschmerztherapie
• Bedarf an Narkosemedikamenten (bei BIS-gesteuerter Anästhesie mit Zielwert: BIS-Index: 40-60)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Woman who undergo abdominal or laparoscopic assisted hysterectomy, or men who undergo radical prostataectomy, as well as woman or men who undergo nephrectomy
2. elective surgery
3. ASA 1-3
4. at least 18 years old
5.negative pregnancy test (nephrectomy in women of childbearing age)
6. capacity
7. Existence of a written informed consent of the patient

1. Frauen, die sich einer abdominellen oder laparoskopisch unterstützen Gebärmutterentfernung unterziehen oder Männer, die sich einer radikalen Prostatektomie unterziehen, sowie Frauen oder Männer die sich einer Nephrektomie unterziehen
2. elektive Operation
3. ASA 1-3
4. mindestens 18 Jahre alt
5. negativer Schwangerschaftstest (Nephrektomie bei Frauen im gebärfähigen Alter)
6. Geschäftsfähigkeit
7. Vorliegen einer schriftlichen Einwilligungserklärung des Patienten

E.4

Principal exclusion criteria

1. Participation in other interventional trials,
2. Contraindications according to prescribing information
- paralytic ileus
- anamnese to a serotonery syndrom
- acute intoxication with alcohol, centrally acting analgesics or psychotropic substances
3. systemic opioid maintenance therapy within the last 4 weeks
4. Clinically significant hepatic and / or renal failure
5. Intolerance to one of the other drugs used in the study (propofol, fentanyl, remifentanil, morphine, rocuronium, etoricoxib)
6. cognitive disability or language barriers that impede adequate communication with the patient
7. People who are in a dependency / employment with the sponsor or investigator

1. Teilnahme an anderen interventionellen Prüfungen
2. Kontraindikationen gemäß Fachinformation
- paralytischer Ileus
- Anamnese eines serotonergen Syndroms
- akute Intoxikation mit Alkohol, zentral wirksamen Analgetika oder psychotropen Substanzen
3. systemische Opioiddauertherapie innerhalb der letzten 4 Wochen
4. klinisch relevante Leber- und/oder Niereninsuffizienz
5. Unverträglichkeiten gegen eines der anderen im Rahmen der Studie verwendeten Medikamente (Propofol, Sufentanil, Remifentanil, Morphin, Rocuronium, Etoricoxib)
6. kognitive Behinderung oder Sprachbarriere, die eine ausreichende Verständigung mit dem Patienten behindern
7. Teilnahme an einer anderen klinischen Studie, die die Durchführung dieser Studie beeinträchtigt

E.5 End points

E.5.1

Primary end point(s)

cumulative Simplified PONV Impact Scale Score [Wengritzky 2012] as "area under the curve (AUC)”

Kumulativer Simplified PONV Impact Scale Score [Myles, Wengritzky 2012] als “area under the curve (AUC)”.

E.5.1.1

Timepoint(s) of evaluation of this end point

1 h, 2 h, 4 h, 12 h, 24 h, 36 h und 48 h postoperative

1 h, 2 h, 4 h, 12 h, 24 h, 36 h und 48 h postoperativ

E.5.2

Secondary end point(s)

• SDS scores for opioid-associated adverse events in the dimensions severity, frequency, and subjective burden [Apfelbaum 2004]
• HORQ-scores for satisfaction and activity level according description in [Apfelbaum 2004]
• Total score of PPP33 questionnaire [Eberhart 2004]
• Total score of PPP16 FT-questionnaire [Eberhart 2008]
• SF-12 questionnaire
• analgesic consumption
• measuring pain (numerical rating scale of 0 to 10)
Additional outcomes:
• Duration of opioid pain therapy
• need for anesthetic drugs (for BIS-guided anesthesia with target: BIS Index: 40-60)

• SDS-Scores für opioidassoziierte Nebenwirkungen in den Dimensionen Schwere, Häufigkeit, subjektive Belastung [Apfelbaum 2004]
• HORQ-Scores für Zufriedenheit und Aktivitätsniveau nach der Be-schreibung in [Apfelbaum 2004]
• Summenscore des PPP33-Fragebogens [Eberhart 2004]
• Summenscore des PPP16-FT-Fragebogens [Eberhart 2008]
• SF-12-Fragebogen
• Schmerzmittelverbrauch über die Tapentadolmedikation hinaus (er-mittelt via PCA-Technik)
• Schmerzmessung (numerische Ratingskala von 0 bis 10)
Weitere Zielgrößen:
• Dauer der Opioidschmerztherapie
• Bedarf an Narkosemedikamenten (bei BIS-gesteuerter Anästhesie mit Zielwert: BIS-Index: 40-60)

E.5.2.1

Timepoint(s) of evaluation of this end point

0-28 days in advance of operation
V1: in advance of anesthesia
V2: 1 hour after operation/extubation
V3: after 2 hours
V4: after 4 hours
V5: after 12 hours
V6: after 24 hours
V7: after 36 hours
V8: after 48 hours
V9: after 60 hours
V10,... : daily until resolution of pain/release
last visit: 12 hours after resolution

0-28 Tage vor Operation
V1: vor der Anästhesie
V2: 1 Stunde nach der Operation / Extubation
V3: nach 2 Stunden
V4: nach 4 Stunden
V5: nach 12 Stunden
V6: nach 24 Stunden
V7: nach 36 Stunden
V8: nach 48 Stunden
V9: nach 60 Stunden
V10, ... : Täglich bis zum Abklingen der Schmerzen / release
letzter Besuch: 12 Stunden nach Beendigung

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)

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

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

Yes

E.8.2.3.1

Comparator description

Morphin

morphine

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

24 months after inclusion of last subject

24 Monate nach Einschluss des letzten Studienteilnehmers

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:

150

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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 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 2012-12-07.

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

150

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)

The patient will be treated with standard therapie.

Der Patient der von der Studie zurücktritt wird mit der Standardtherapie weiterbehandelt

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

2013-08-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-06-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-09-30

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