Clinical Trials Register

Summary
EudraCT Number:	2011-004235-31
Sponsor's Protocol Code Number:	SEVICONTROL-1
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:	2011-09-22
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

2011-004235-31

A.3

Full title of the trial

SEVICONTROL-1:
Efficacy and safety of a fixed combination of olmesartan 40 mg/amlodipin 10 mg in patients with moderate essential hypertension not sufficiently controlled under monotherapy with candesartan 32 mg - an open phase IIIb trial

SEVICONTROL-1:
Wirksamkeit und Sicherheit einer Fixkombination Olmesartan 40 mg / Amlodipin 10 mg bei Patienten mit einer unter Candesartan 32 mg Monotherapie unzureichend kontrollierter moderater essentieller Hypertonie – eine offene Phase IIIb – Studie

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

SEVICONTROL-1

A.4.1

Sponsor's protocol code number

SEVICONTROL-1

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	IPPMed GmbH
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	Daiichi Sankyo Deutschland GmbH
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	IPPMed GmbH
B.5.2	Functional name of contact point	IPPMed
B.5.3	Address:
B.5.3.1	Street Address	Menzelstraße 21
B.5.3.2	Town/ city	Mahlow
B.5.3.3	Post code	15831
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49033793147890
B.5.5	Fax number	+49033793147892
B.5.6	E-mail	peter.bramlage@ippmed.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	Atacand 16 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Astra Zeneca Deutschland GmbH
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.3.4	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.3.8	INN - Proposed INN	CANDESARTAN
D.3.9.1	CAS number	139481-59-7
D.3.9.4	EV Substance Code	SUB06070MIG
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	16
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	Atacand Protect 32 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Astra Zeneca Deutschland GmbH
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.3.4	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.3.8	INN - Proposed INN	CANDESARTAN
D.3.9.1	CAS number	139481-59-7
D.3.9.4	EV Substance Code	SUB06070MIG
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	32
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: 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	Sevikar 40/5 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Daiichi Sankyo Deutschland GmbH
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.3.4	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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	144689-63-4
D.3.9.3	Other descriptive name	OLMESARTAN MEDOXOMIL
D.3.9.4	EV Substance Code	SUB03508MIG
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	40
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	AMLODIPINE
D.3.9.1	CAS number	88150-42-9
D.3.9.4	EV Substance Code	SUB05467MIG
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	5
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: 4
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	Sevikar 40/10 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Daiichi Sankyo Deutschland GmbH
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.3.4	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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	144689-63-4
D.3.9.3	Other descriptive name	OLMESARTAN MEDOXOMIL
D.3.9.4	EV Substance Code	SUB03508MIG
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	40
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	AMLODIPINE
D.3.9.1	CAS number	88150-42-9
D.3.9.4	EV Substance Code	SUB05467MIG
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	10
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 essential arterial hypertension

moderate essentielle arterielle Hypertonie

E.1.1.1

Medical condition in easily understood language

Elevated Blood Pressure

erhöhter Blutdruck

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10015491
E.1.2	Term	Essential hypertension, unspecified
E.1.2	System Organ Class	10047065 - Vascular disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	PT
E.1.2	Classification code	10020772
E.1.2	Term	Hypertension
E.1.2	System Organ Class	10047065 - Vascular 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

Efficacy in blood pressure reduction and safety of a direct switch from candesarten to a fixed combination of olmesartan and amlodipin.

Wirksamkeit der Blutdrucksenkung und die Sicherheit einer direkten Umstellung von Candesartan auf eine Fixkombination von Olmesartan/Amlodipin.

E.2.2

Secondary objectives of the trial

Comparison of evening to morning application of olmesartan 40 mg/amlodipin 10 mg with regard to improving the circadian blood pressure profile and the safety of the fixed combination.

Vergleich der abendlichen mit der morgendlichen Einnahme von Olmesartan 40mg / Amlodipin 10mg im Hinblick auf eine Verbesserung des zirkadianen Blutdruckprofils und der Sicherheit der Fixkombination.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

male or female patients >= 18 years of age

essential hypertension, i. e. systolic office bp >= 140 mmHg for pre-treated patients or >= 160 mmHg for untreated patients at screening visit and >= 160 mmHg at end of wash-out

signed IC

Frauen oder Männer ≥ 18 Jahre mit essentieller Hypertonie und Blutdruckwerten in der OBDM ≥ 140 mmHg systolisch zur Screening Visite 1 bei vorhergehender antihypertensiver Monotherapie oder ≥ 160 mm Hg systolisch ohne Vortherapie und ≥ 160 mm Hg systolisch am Ende der Auswaschphase

unterzeichnete Einverständniserklärung

E.4

Principal exclusion criteria

• systolic office bp > 180 mm Hg at screening visit
• known hypertensive retinopathy GIII or IV
• recent (< 4 weeks ago) myocardial infarction or indication for coronary or peripheral revascularisation
• type I diabetes or poorly controlled (HbA1c > 8) type II diabetes
• chronic heart failure NYHA III or IV
• prior stroke or TIA
• creatinine clearance < 60 ml/min or condition after kidney transplant
• moderately or severely impaired liver function (ALT or AST or bilirubin more than double normal value)
• women of childbearing potential without highly effective contraception, pregnant or breastfeeding women
• concomitant therapy with lithium
• hemodynamically relevant mitral or aortic valve stenosis (>= II°) or hypertrophic obstructive cardiomyopathy
• concomitant therapy with strong CYP3A4 inhibitors or inductors
• african patients
• concomitant severe psychiatric condition that might impair proper intake of study medication
• life expectancy < 6 months
• night shift workers
• known other mandatory indication for treatment with antihypertensive medications

• Blutdruck systolisch > 180 mm Hg in der OBDM zur Screening Visite 1
• Bekannte hypertensive Retinopathie G III oder IV
• Myokardinfarkt innerhalb der letzten 4 Wochen bzw. Indikation für eine koronare oder periphere Revaskularisation
• Typ 1 Diabetes mellitus, Typ 2 Diabetes mellitus mit schlechter Blutzuckereinstellung (HbA1c ≥ 8)
• Herzinsuffizienz NYHA III und IV
• Z. n. Schlaganfall oder transitorisch ischämische Attacke
• Kreatinin-Clearance < 60 ml/min oder Z. n. Nierentransplantation
• Patienten mit mäßiger oder stark eingeschränkter Leberfunktion (ALT oder AST oder Bilirubin mehr als 2-fach über den oberen Normwert)
• Gebärfähige Fauen, ohne hocheffektive Schwangerschaftsverhütung, Schwangere und stillende Mütter
• Therapie mit Lithium
• Hämodynamisch relevante Mitral-oder Aortenstenose (≥Grad II) bzw. Hypertrophe Obstruktive Kardiomyopathie
• Gleichzeitige Therapie mit starken CYP3A4-Induktoren sowie starken CYP3A4-Inhibitoren
• Patienten mit schwarzer Hautfarbe
• Schwere psychiatrische Begleiterkrankung, die eine ordnungsgemäße Einnahme der Studienmedikation behindern könnte
• Lebenserwartung < 6 Monate
• Nachtschichtarbeiter
• Bestehende andere absolute Indikation zur Gabe eines Medikamentes mit blutdrucksenkender Wirkung

E.5 End points

E.5.1

Primary end point(s)

Reduction in systolic day-time mean APBM values after 6 weeks treatment with the fixed combination of 40 mg olmesartan and 10 mg amlodipin as compared to previous monotherapy with candesartant

Senkung des systolischen Tagesmittelwertes in der ABDM nach 6 Wochen Therapie mit einer fixen Kombination aus Olmesartan 40mg und Amlodipin 10mg im Vergleich zur vorhergehenden Monotherapie mit Candesartan

E.5.1.1

Timepoint(s) of evaluation of this end point

6 weeks after switch from candesartan monotherapy to treatment with fixed combination

6 Wochen nach Wechsel von der Monotherapie auf die Fixkombination

E.5.2

Secondary end point(s)

reduction of the ratio of non-dippers/inverted dippers

Reduktion des Anteils von Non-dippern / Inverted Dippern

E.5.2.1

Timepoint(s) of evaluation of this end point

6 weeks after switching from morning to evening intake of the fixed combination of olmesartan 40 mg and amlodipine 10 mg

nach 6 Wochen abendlicher Einnahme der fixen Kombination aus Olmesartan 40mg und Amlodipin 10mg im Vergleich zur vorhergehenden morgendlichen Einnahme.

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

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.2.3

Other

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

The trial may be interrupted or ended prematurely in if sponsor and principal investigator agree that this is necessary with regard to the cost/risk ratio.
The sponsor also reserves the right to end the trial for formal reasons (i. e. insufficient recruitment rates, non-compliance with the timeline, unfulfilled agreements, missing or lacking documentation).

Die gesamte Studie kann in Abstimmung zwischen Sponsor und dem Leiter der klinischen Prüfung unter Abwägung des Nutzen/Risiko-Verhältnisses unterbrochen oder beendet werden.
Der Sponsor behält sich vor, die Studie jederzeit auch aus formellen Gründen zu beenden (z. B. mangelnde Rekrutierung, nicht eingehaltener Studienzeitplan, nicht erfüllte Vereinbarungen, fehlende oder mangelhafte Dokumentation).

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.2.1	Number of subjects for this age range:	80
F.1.3	Elderly (>=65 years)	No
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	80

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

2011-12-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-10-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-09-24

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