Clinical Trials Register

Summary
EudraCT Number:	2023-000135-76
Sponsor's Protocol Code Number:	ACE-01-22
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2023-03-06
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2023-000135-76

A.3

Full title of the trial

Therapeutic Equivalence Study of Twice Daily Acetylsalicylic Acid Tablets 50 mg Compared to Once Daily Acetylsalicylic Acid Tablets 100 mg in Adult Patients Coronary Artery Disease (CAD) or Symptomatic Peripheral Artery Disease (PAD) or after Acute Coronary Syndrome (ACS)

Badanie równoważności terapeutycznej kwasu acetylosalicylowego w postaci tabletek 50 mg podawanych dwa razy dziennie w porównaniu do tabletek 100 mg podawanych raz dziennie u dorosłych pacjentów z chorobą niedokrwienną serca, chorobą tętnic obwodowych lub po przejściu ostrych zespołów wieńcowych.

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

ACE-01-22

A.4.1

Sponsor's protocol code number

ACE-01-22

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	Adamed Pharma S.A.
B.1.3.4	Country	Poland
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	Adamed Pharma S.A.
B.4.2	Country	Poland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Adamed Pharma S.A.
B.5.2	Functional name of contact point	Punkt Informacyjny Badania
B.5.3	Address:
B.5.3.1	Street Address	ul. M. Adamkiewicza 6A Pienkow
B.5.3.2	Town/ city	Czosnow
B.5.3.3	Post code	05-152
B.5.3.4	Country	Poland
B.5.4	Telephone number	+48726 441 773
B.5.6	E-mail	blanka.seklecka@adamed.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	Yes
D.2.1.1.1	Trade name	HerzASS-ratiopharm® 50 mg tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	ratiopharm 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.3.1	Product name	HerzASS-ratiopharm® 50 mg 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.3.8	INN - Proposed INN	Acetylsalicylic acid
D.3.9.1	CAS number	50-78-2
D.3.9.4	EV Substance Code	SUB12730MIG
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	Aspirin® N 100 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Vital 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.3.1	Product name	Aspirin® N 100 mg
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	Acetylsalicylic acid
D.3.9.1	CAS number	50-78-2
D.3.9.4	EV Substance Code	SUB12730MIG
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

Coronary Artery Disease (CAD) or Symptomatic Peripheral Artery Disease (PAD) or after Acute Coronary Syndrome (ACS)

choroba wieńcowa (CAD) lub objawowa choroba tętnic obwodowych (PAD) lub wystąpienie ostrego zespołu wieńcowego (ACS);

E.1.1.1

Medical condition in easily understood language

Coronary Artery Disease (CAD) or Symptomatic Peripheral Artery Disease (PAD) or after Acute Coronary Syndrome (ACS)

choroba wieńcowa (CAD) lub objawowa choroba tętnic obwodowych (PAD) lub wystąpienie ostrego zespołu wieńcowego (ACS);

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10011078
E.1.2	Term	Coronary artery disease
E.1.2	System Organ Class	10007541 - Cardiac disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10067825
E.1.2	Term	Peripheral arterial disease
E.1.2	System Organ Class	10047065 - Vascular disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10051592
E.1.2	Term	Acute coronary syndrome
E.1.2	System Organ Class	10007541 - Cardiac 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

To evaluate equivalence in inhibiting platelet aggregation and platelet thromboxane production between acetylsalicylic acid tablets 50 mg administered twice daily and acetylsalicylic acid tablets 100 mg administered once daily.

Ocena równoważności w hamowaniu agregacji płytek i wytwarzania tromboksanu przez płytki pomiędzy kwasem acetylosalicylowym w postaci tabletek 100 mg podawanym raz na dobę a kwasem acetylosalicylowym w postaci tabletek w dawce 50 mg podawanym dwa razy na dobę.

E.2.2

Secondary objectives of the trial

• To evaluate sTxB2 levels and platelet aggregation response in obese and non-obese patients
• To evaluate pharmacodynamics of sTxB2 in patients receiving acetylsalicylic acid tablets 50 mg twice daily and acetylsalicylic acid tablets 100 mg once daily (optional for patients who sign separate Informed Consent Form for additional biological material collection)
• To evaluate safety

• Ocena poziomu sTxB2 i odpowiedzi na agregację płytek krwi u pacjentów otyłych i nieotyłych
• Ocena farmakodynamiki sTxB2 u pacjentów otrzymujących tabletki kwasu acetylosalicylowego 50 mg dwa razy dziennie oraz tabletki kwasu acetylosalicylowego 100 mg raz dziennie (opcjonalnie dla pacjentów, którzy podpiszą oddzielny formularz świadomej zgody na dodatkowe pobranie materiału biologicznego)
• Ocena bezpieczeństwa

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. diagnosis of coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) or recent occurrence of acute coronary syndrome (ACS);
2. age of ≥18 years old;
3. patients who were prescribed ASA EC tablets 100 mg or ASA IR tablets 100 mg or ASA EC tablets 75 mg or ASA IR tablets 75 mg and in the opinion of the Principal Investigator
can be switched to ASA IR tablets 100 mg.

1. rozpoznanie choroby wieńcowej (CAD) lub objawowej choroby tętnic obwodowych (PAD) lub niedawne wystąpienie ostrego zespołu wieńcowego (ACS);
2. wiek ≥18 lat;
3. pacjenci, którym przepisano ASA EC tabletki 100 mg lub ASA IR tabletki 100 mg lub ASA EC tabletki 75 mg lub ASA IR tabletki 75 mg i w opinii Głównego Badacza można je zmienić na tabletki ASA IR w dawce 100 mg.

E.4

Principal exclusion criteria

1. blood disorders;
2. aspirin resistance (>550 ARU on VerifyNow® Aspirin Test);
3. patients treated with oral anticoagulants, thrombolytic agents, non-steroidal anti-inflammatory drugs in the period <7 days before randomization
4. patients treated with heparin (including perioperative heparin) in the period <1 day before randomization and during the course of the study
5. indication for the use of low-molecular-weight heparin (LMWH)
6. concurrent administration of drugs that are potent inhibitors of Cytochrome P450 3A (CYP 3A)
7. recent antiplatelet treatment (< 30 days) with a glycoprotein IIb/IIIa antagonist;
8. history of gastrointestinal bleeding within the last 6 months;
9. history of cerebrovascular accident within the last 3 months;
10. active bleeding or hemodynamic instability;
11. any active malignancy recent surgery (within one month) including central nervous system (CNS) surgeries like lumbar puncture;
12. baseline ALT >2.5 times the upper limit of normal;
13. platelet count ≥600 × 103/ mm3 or ≤150 × 103/mm3;
14. hematocrit ≥50% or ≤25%;
15. low compliance before enrolment;
16. uncontrolled diabetes mellitus (stable drug doses within last 3 months before randomization);
17. end stage kidney disease with glomerular filtration rate
<15 mL/min or on hemodialysis;
18. pregnant or lactating women, or women of childbearing potential not practising an adequate method of contraception e.g., intrauterine device, oral contraception or progesterone implant. Pregnancy must be excluded by a negative pregnancy test at Visit 1;
19. renal artery stenosis or kidney transplantation;
20. hypersensitivity to any component of the investigational products;
21. chronic liver disease;
22. concomitant or previous treatment with any other investigational drug within 20 days of enrolment;
23. as per the Investigator (or his designee) judgment, subject cannot participate in the study for any reason (e.g., medical, psychiatric and/or social reason).

1. choroby krwi;
2. oporność na aspirynę (≥550 ARU w teście VerifyNow® Aspirin);
3. pacjenci leczeni doustnymi antykoagulantami, środkami trombolitycznymi, niesteroidowymi lekami przeciwzapalnymi w okresie <7 dni przed randomizacją
4. pacjenci leczeni heparyną (w tym heparyną okołozabiegową) w okresie <1 dnia przed randomizacją i w trakcie trwania badania
5. wskazanie do stosowania heparyny drobnocząsteczkowej (ang. low-molecular-weight heparyn, LMWH)
6. równoległe podawanie leków będących silnymi inhibitorami Cytochromu P450 3A (CYP 3A)
7. niedawne leczenie przeciwpłytkowe (< 30 dni) antagonistą glikoproteiny IIb/IIIa;
8. krwawienie z przewodu pokarmowego w wywiadzie w ciągu ostatnich 6 miesięcy;
9. incydent naczyniowo-mózgowy w wywiadzie w ciągu ostatnich 3 miesięcy;
10. aktywne krwawienie lub niestabilność hemodynamiczna;
11. jakikolwiek czynny nowotwór złośliwy niedawno przebyta operacja (w ciągu miesiąca), w tym zabiegi chirurgiczne w obrębie ośrodkowego układu nerwowego (OUN), takie jak punkcja lędźwiowa;
12. wyjściowy poziom ALT >2,5-krotność górnej granicy normy;
13. liczba płytek krwi ≥600 × 103/ mm3 lub ≤150 × 103/mm3;
14. hematokryt ≥50% lub ≤25%;
15. niski poziom przestrzegania zaleceń lekarskich przez pacjenta zaobserwowany przed włączaniem do badania
16. niekontrolowana cukrzyca (stabilne dawki leków w ciągu ostatnich 3 miesięcy przed randomizacją);
17. schyłkowa niewydolność nerek ze wskaźnikiem filtracji kłębuszkowej <15 mL/min lub na hemodializie;
18. kobiety w ciąży lub karmiące, lub kobiety w wieku rozrodczym niestosujące odpowiedniej metody antykoncepcji np. wkładki wewnątrzmacicznej, doustnej antykoncepcji lub implantu progesteronowego. Ciąża musi zostać wykluczona przez ujemny wynik testu ciążowego podczas wizyty nr 1;
19. zwężenie tętnicy nerkowej lub przeszczep nerki;
20. nadwrażliwość na którykolwiek składnik badanych produktów;
21. przewlekła choroba wątroby;
22. udział w jakimkolwiek innym badaniu klinicznym leku w ciągu 20 dni od włączenia do niniejszego badania;
23. według oceny Badacza (lub osoby przez niego wyznaczonej) pacjent nie może uczestniczyć w badaniu z jakiegokolwiek innego powodu (np. medycznego, psychiatrycznego i/lub społecznego).

E.5 End points

E.5.1

Primary end point(s)

1) Difference in sTxB2 levels measured with analytical ELISA methods after 10 days of twice daily ASA 50 mg tablets compared to 10 days of once daily ASA 100 mg tablets.
2) Difference in platelet reactivity measured with VerifyNow® Aspirin Test after 10 days of twice daily ASA 50 mg tablets compared to 10 days of once daily ASA 100 mg tablets .

1) Różnica w poziomach sTxB2 mierzonych analityczą metodą ELISA po 10 dniach podawania dwa razy dziennie tabletek ASA 50 mg w porównaniu do 10 dni podawania raz dziennie tabletek ASA 100 mg.
2) Różnica w reaktywności płytek krwi mierzonej za pomocą VerifyNow® Aspirin Test po 10 dniach podawania dwa razy dziennie tabletek ASA 50 mg w porównaniu do 10 dni podawania raz dziennie tabletek ASA 100 mg.

E.5.1.1

Timepoint(s) of evaluation of this end point

Participants receive treatment and are monitored from the time of randomization until the end of the study. The expected duration of treatment in the study is 20 days, Regular evaluations are scheduled during the study.

Uczestnicy otrzymują leczenie i są monitorowani od czasu randomizacji do zakończenia badania. Przewidywany czas trwania leczenia w badaniu wynosi 20 dni, W trakcie badania zaplanowano regularne oceny.

E.5.2

Secondary end point(s)

1) Difference in sTxB2 levels in subgroup of obese (BMI ≥ 35) patients
2) Difference in platelet reactivity in subgroup of obese (BMI ≥ 35) patients
3) Difference in sTxB2 levels in subgroup of non-obese patients
4) Difference in platelet reactivity in subgroup of non-obese patients
5) Difference in pharmacokinetics measured with % of maximal TxB2 inhibition (Imax)
6) Difference in pharmacokinetics measured with TxB2 AUC0-24
7) Safety assessment. The number of AE/SAE after twice daily ASA 50 mg tablets compared to once daily ASA 100 mg tablets.

1) Różnica w stężeniu sTxB2 w podgrupie pacjentów otyłych (BMI ≥ 35)
2) Różnica w reaktywności płytek krwi w podgrupie pacjentów otyłych (BMI ≥ 35)
3) Różnica w poziomie sTxB2 w podgrupie pacjentów bez otyłości
4) Różnica w reaktywności płytek krwi w podgrupie pacjentów bez otyłości
5) Różnica w farmakokinetyce mierzonej w % maksymalnego zahamowania TxB2 (Imax)
6) Różnica w farmakokinetyce mierzonej za pomocą AUC0-24
7) Ocena bezpieczeństwa. Liczba AE/SAE po podaniu dwa razy dziennie tabletek ASA 50 mg w porównaniu z raz dziennie tabletek ASA 100 mg.

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary endpoints will be assessed throughout the study

Wtórne punkty końcowe będą oceniane przez cały czas trwania badania

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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

Yes

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

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)

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

Last Visit Last Subject (LVLS)

Ostatnia wizyta ostatniego uczestnika badania klinicznego (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:

130

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

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

220

F.4.2

For a multinational trial

F.4.2.1

In the EEA

220

F.4.2.2

In the whole clinical trial

220

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)

Once the anticipated cutoff date for the evaluation has been reached, an on-site visit to the facility will be made to determine the appropriate therapy, according to the clinical standard of care.

Po ustaleniu przewidywanej daty odcięcia oceny przeprowadzeniu wizyty na miejscu w ośrodku, nastąpi ustalenie odpowiedniej terapii, zgodnie z klinicznym standardem opieki.

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

2023-05-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-03-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-10-11

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Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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