Clinical Trials Register

Summary
EudraCT Number:	2013-001974-11
Sponsor's Protocol Code Number:	HEPATOTEST
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:	2013-07-12
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

Spain - AEMPS

A.2

EudraCT number

2013-001974-11

A.3

Full title of the trial

PILOT TRIAL FOR THE EVALUATION OF HEPATOTEST IN PREOPERATIVE ASSESSMENT IN LIVER FUNCTION.

ESTUDIO PILOTO PARA LA EVALUACIÓN DEL HEPATOTEST EN LA VALORACIÓN PREOPERATORIA DE LA FUNCIÓN HEPÁTICA

A.3.1

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

PILOT TRIAL FOR THE EVALUATION OF HEPATOTEST IN PREOPERATIVE ASSESSMENT IN LIVER FUNCTION.

ESTUDIO PILOTO PARA LA EVALUACIÓN DEL HEPATOTEST DE LA FUNCION HEPATICA PREOPERATORIA.

A.4.1

Sponsor's protocol code number

HEPATOTEST

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	INSTITUTO DE INVESTIGACION SANITARIA LA FE
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 INVESTIGACION SANITARIA LA FE
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 INVESTIGACION SANITARIA LA FE
B.5.2	Functional name of contact point	UREC
B.5.3	Address:
B.5.3.1	Street Address	BULEVAR S/N
B.5.3.2	Town/ city	VALENCIA
B.5.3.3	Post code	46026
B.5.3.4	Country	Spain
B.5.4	Telephone number	34961246611
B.5.5	Fax number	96961246620
B.5.6	E-mail	investigacion_clinica@iislafe.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	FRENADOL COMPLEX
D.2.1.1.2	Name of the Marketing Authorisation holder	Johnson & Johnson S.A
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	Powder for oral solution
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	PARACETAMOL
D.3.9.3	Other descriptive name	N02BE01
D.3.9.4	EV Substance Code	SUB09611MIG
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	650
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DEXTROMETHORPHAN
D.3.9.1	CAS number	125-71-3
D.3.9.4	EV Substance Code	SUB07051MIG
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	20
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CAFFEINE CITRATE
D.3.9.1	CAS number	69-22-7
D.3.9.3	Other descriptive name	CAFFEINE CITRATE
D.3.9.4	EV Substance Code	SUB13151MIG
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	30
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CHLORPHENAMINE
D.3.9.1	CAS number	132-22-9
D.3.9.4	EV Substance Code	SUB06201MIG
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	4
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	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.2.1.1.1	Trade name	ICG-PULSION
D.2.1.1.2	Name of the Marketing Authorisation holder	PULSION Medical Systems
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INDOCYANINE GREEN
D.3.9.1	CAS number	3599-32-4
D.3.9.3	Other descriptive name	INDOCYANINE GREEN
D.3.9.4	EV Substance Code	SUB14208MIG
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	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	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

Patients with liver metastases (mainly colorectal cancer) who will be undergoing major hepatic resection (3 or more liver segments) which have been treated with neoadjuvant chemotherapy.

Pacientes con metástasis hepáticas (principalmente de cáncer colorrectal) que vayan a ser sometidos a resección hepática mayor (3 o más segmentos hepáticos) y que hayan recibido tratamiento con quimioterapia neoadyuvante.

E.1.1.1

Medical condition in easily understood language

Patients with metastases in the liver who have removing a segment.

Pacientes con metastasis en el hígado que vayan a extirparles un segmento de su hígado.

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05]

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

Evaluate the effectiveness of Hepatotest in assessing preoperative liver function in patients with liver metastases who have received chemotherapy. The correlation of active ingredients and metabolites in blood and urine, and liver enzyme activity in liver biopsy will be studied.

Evaluar la eficacia del Hepatotest en la valoración de la función hepática preoperatoria en pacientes con metástasis hepáticas que hayan recibido tratamiento con quimioterapia. Se estudiará la correlación de principios activos y metabolitos en sangre y orina, y la actividad enzimática hepática en biopsia hepática.

E.2.2

Secondary objectives of the trial

Patient Group:study the metabolism of the active principles of the drug and indocyanine green test before and after chemotherapy before surgery,and determining differences.Results of HepatoTest will correlated with indocyanine green test performed before and after chemotherapy.Determine the pharmacokinetics of paracetamol active,dextromethorphan, chlorpheniramine and caffeine volunteer subjects.Liver biopsy study the amount and activity per gram of tissue of the enzymes involved in the metabolism of the active principles of the drug.To determine the relationship of the results of HepatoTest and indocyanine green test with the appearance of postoperative liver dysfunction.Determine the histological changes secondary to chemotherapy,and its relation to the type of chemotherapy received, the duration of treatment,and the occurrence of postoperative liver dysfunction.Study the correlation of preoperative HepatoTest result of hepatic enzyme activity in liver regeneration capacity

Grupo pacientes:estudiar metabolismo d los principios activos del fármaco y del test verde de indocianina antes y dp de la quimio, previa a la cirugía,deter las diferencias.Correlacionar los resultados del HepatoTest con los de la indocianina realizados antes y tras quimio.Deter l farmacocinética de los principios activos paracetamol,dextrometorfano, clorfenamina y cafeína en sujetos volunt.Estudiar mediante biopsia la cantidad y actividad por gr de tejido de los enzimas implicados en el metabolismo de los principios activos del fármaco.Determinar la relación de los resultados del HepatoTest y test indocianina con la aparición de disfunción hepática postoperatoria.Estudio anatomopatológico de las biopsiaspara determinar los cambios histológicos secundarios a quimio,su relación quimioterápico recibido, duración del tratamiento,aparición de disfunción postoperatoria.Estudiar la correlación del resultado del HepatoT preoperatorio y l actividad enzimática con la capacidad de regeneración

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Group volunteers: volunteer subjects without associated liver pathology.
Group patients: Patients with liver metastases (mainly colorectal cancer) who will be undergoing major hepatic resection (3 or more liver segments) which have been treated with neoadjuvant chemotherapy

Grupo voluntarios: Sujetos voluntarios sin patología hepática asociada.
Grupo pacientes: Pacientes con metástasis hepáticas (principalmente de cáncer colorrectal) que vayan a ser sometidos a resección hepática mayor (3 o más segmentos hepáticos) y que hayan recibido tratamiento con quimioterapia neoadyuvante.

E.4

Principal exclusion criteria

Volunteer Group: Under 18 years, pregnant and lactating women, allergy to any of the active substances or excipients, allergy to acetylsalicylic acid, associated liver disease (cirrhosis, hepatitis, liver tumor pathology), moderate alcohol consumption, renal failure (creatinine 1.2mg/dl or GFR of less than 90 ml / min), use of drugs that interfere with the hepatic metabolism of the active
Patients Group: Under 18 years, allergy to any of the active substances or excipients or indocyanine green, allergy to acetylsalicylic acid, total bilirubin high (greater than 1.1 mg / dl), liver cirrhosis, renal failure (creatinine greater than 1.2mg/dl or GFR of less than 90 ml / min), progression of metastatic disease or the appearance of other pathological conditions contraindicate study during surgery.

Grupo voluntarios: Menores de 18 años, embarazadas y mujeres en periodo de lactancia, alergia a alguno de los principios activos o excipientes, alergia a ácido acetil salicílico, patología hepática asociada (cirrosis, hepatitis, patología tumoral hepática), consumo de alcohol moderado, insuficiencia renal (creatinina mayor de 1.2mg/dl o filtrado glomerular menor de 90 ml/min), consumo de fármacos que interfieran en el metabolismo hepático de los principios activos
Grupo pacientes: Menores de 18 años, alergia a alguno de los principios activos o excipientes o verde indocianina, alergia a ácido acetil salicílico, bilirrubina total elevada (mayor de 1,1 mg/dl), cirrosis hepática, insuficiencia renal (creatinina mayor de 1.2mg/dl o filtrado glomerular menor de 90 ml/min), progresión de la enfermedad metastásica o aparición de otras circunstancias patológicas durante el estudio que contraindiquen la cirugía.

E.5 End points

E.5.1

Primary end point(s)

Correlation of active ingredients and metabolites in blood and urine, and liver enzyme activity in liver biopsy.

Correlación de principios activos y metabolitos en sangre y orina, y la actividad enzimática hepática en biopsia hepática

E.5.1.1

Timepoint(s) of evaluation of this end point

At the end of the clinical trial.

Al final del estudio.

E.5.2

Secondary end point(s)

Determination of metabolites before and after chemotherapy in both tests.
Compare the results of both tests before and after chemotherapy.
Determine the drug pharmacokinetics in healthy volunteers

Determinacion de los metabolitos antes y despues de la quimioterapia en ambos test.
Comparar los resultados de ambos test antes y despues de la quimioterapia.
Determinar la farmacinetica del fármaco en voluntarios sanos

E.5.2.1

Timepoint(s) of evaluation of this end point

At the end of the clinical trial.

Al final del estudio.

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

E.6.5

Efficacy

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

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

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

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)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

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)

The plans for treatment at the end of the trial is not different from the expected normal treatment of that condition.

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

2013-08-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-05-28

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials