Clinical Trials Register

Summary
EudraCT Number:	2018-002101-65
Sponsor's Protocol Code Number:	PI17/01109
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2018-07-17
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

Spain - AEMPS

A.2

EudraCT number

2018-002101-65

A.3

Full title of the trial

Assessment of direct biomarkers of aspirin action to develop a precision chemoprevention therapy of colorectal cancer

Evaluación de biomarcadores de acción directa del ácido acetilsalicílico para el desarrollo de quimioprevención personalizada en el cáncer colorrectal

A.3.1

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

Assessment of aspirin for the prevention of colorectal cancer

Evaluación de la aspirina en la prevención del cáncer colorrectal

A.4.1

Sponsor's protocol code number

PI17/01109

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1214-4083

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	Ángel Lanas Arbeloa-Instituto de Investigación Sanitaria Aragón
B.1.3.4	Country	Spain
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	Instituto de Salud Carlos III
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Instituto de Investigación Sanitaria Aragón
B.5.2	Functional name of contact point	Unidad de Investigación Clínica
B.5.3	Address:
B.5.3.1	Street Address	Avda. San Juan Bosco 13, planta 0
B.5.3.2	Town/ city	Zaragoza
B.5.3.3	Post code	50009
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034976716582
B.5.6	E-mail	emlopezh@iisaragon.es

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	Adiro 100 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Hispania, S.L.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	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.3.8	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.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	Adiro 300 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Hispania, S.L.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	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.3.8	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	300
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

Colorectal cancer with a recent confirmed diagnosis (less than 48h)

Cáncer colorrectal con un diagnóstico confirmado reciente (menos de 48h)

E.1.1.1

Medical condition in easily understood language

colorectal cancer

cáncer colorrectal

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

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	10061451
E.1.2	Term	Colorectal cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 perform a study of acetylsalicylic acid by using a proteomic assay for comparing platelet COX-1 and colorectal cancer mucosal COX-1 and COX-2 after different doses of acetylsalicylic acid

evaluar, mediante un ensayo proteómico, el efecto directo de dosis diferentes de ácido acetilsalicílico sobre COX-1 y COX-2 en plaquetas, tejido colonice sano y tumoral como biomarcadores de eficiencia clínica

E.2.2

Secondary objectives of the trial

measurement of PGE2 and p-S6 levels in colorectal cancer mucosa, assessment of indirect biomarkers of acetylsalicylic acid action (serum TXB2, PFA and urinary levels of 11-dehydro-TXB2, (TX-M)), evaluation of systemic biomarkers of inflammatory/tumorigenic COX-2 by assessing urinary levels of major metabolite of PGE2 (PGE-M)

evaluar el efecto del ácido acetilsalicílico en los niveles de PGE2 y p-S& en la mucosa del cáncer colorrectal, estudiar el efecto sobre biomarcadores indirectos de su acción a nivel sistémico (TXB2, PFA y niveles urinarios de 11-deshidro-TXB2 (TX-M)) y analizar biomarcadores sistémicos de actividad de COX-2 inflamatoria/tumorigénica mediante la evaluación de niveles urinarios del principal metabolito de PGE2 (PGE-M)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Age from 18 to 80 years old
- Recent diagnosis (less than 48h) of colorectal cancer by endoscopy and confirmed by anatomopathological study
- normal hematologic, biochemical, and coagulation values

- edad entre 18 y 80 años
- diagnóstico reciente (menos de 48h) de cáncer colorrectal mediante endoscopia y confirmado por estudio anatomopatológico
- parámetros hematológicos, bioquímicos y de coagulación normales

E.4

Principal exclusion criteria

- Allergy to AAS or to any other NSAID.
- Rectal cancer requiring neoadjuvant treatment wthin the two weeks following the beginning of ASA treatment.
- Previous use of AAS, NSAIDs, antiplatelet agents, corticosteroids or misoprostol within the 15 days prior to diagnosis and/or anticipation of need for treatment with any of these drugs during the study period.
History of peptic ulcer disease or active peptic ulcer or any other GI disease that may be considered a contraindication to the use of ASA, without the concomitant use of proton pump inhibitors.
- Diagnosis of bleeding disorders.
- Diagnosis of cancer (excluding non-melanoma skin cancer) during the previous 3 years.
- Conditions supposing serious comorbidity, excluding diabetes, and including respiratory, cardiac, hepatic and renal diseases.
- Active smoking.
- Pregnancy or breastfeeding.
- History of drug or alcohol abuse.

- Alergia a AAS o a algún otro AINE.
- Cáncer rectal que requiera tratamiento neoadyuvante en las dos semanas siguientes al inicio del tratamiento con AAS.
- Uso previo de AAS, AINEs, agentes antiplaquetarios, corticosteroides o misoprostol en los 15 días anteriores al diagnóstico y/o previsión de necesidad de tratamiento con alguno de estos fármacos durante el periodo de estudio.
- Historia de úlcera péptica o úlcera péptica activa o cualquier otra enfermedad GI que pueda considerarse contraindicación para el uso de AAS, sin el uso concomitante de inhibidores de la bomba de protones.
- Diagnóstico de trastornos hemorrágicos.
- Diagnóstico de cáncer (excluyendo cáncer de piel no melanoma) en los 3 años previos.
- Condiciones que supongan comorbilidad grave, excluyendo diabetes, e incluyendo enfermedades respiratorias, cardiacas, hepáticas y renales.
- Tabaquismo activo.
- Situación de embarazo o lactancia.
- Historia de consumo de drogas o abuso de alcohol.

E.5 End points

E.5.1

Primary end point(s)

Assessment of acetylation level of COX enzymes in platelets and non-neoplastic and neoplastic colonic tissues

Evaluación del nivel de acetilación de las enzimas COX en plaquetas y tejido colónico sano y tumoral

E.5.1.1

Timepoint(s) of evaluation of this end point

before the beginning of the treatment and 3-4 weeks of acetylsalicylic acid treatment

antes del comienzo del tratamiento y tras 3-4 semanas de tratamiento con ácido acetilsalicílico

E.5.2

Secondary end point(s)

assessment of PGE2 level and S6 protein phosphorylation state in colorectal mucosa depending on AAS dosis and assessment of dosis effect e¡over indirect biomarkers

Evaluación del nivel de PGE2 y del estado de fosforilación de la proteína S6 en mucosa colorrectal dependiendo de la dosis de AAS y evaluación del efecto de la dosis de AAS sobre biomarcadores indirectos a nivel sistémico

E.5.2.1

Timepoint(s) of evaluation of this end point

before the beginning of the treatment and 3-4 weeks of acetylsalicylic acid treatment

antes del comienzo del tratamiento y tras 3-4 semanas de tratamiento con ácido acetilsalicílico

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

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

Yes

E.8.2.3.1

Comparator description

diferentes dosis del mismo producto

different dosage of the same product

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

LVLS

la última visita del último participante del ensayo clínico

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:

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

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

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)

none

ninguno

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

2018-11-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-10-16

P. End of Trial
P.	End of Trial Status	Ongoing

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