Clinical Trials Register

Summary
EudraCT Number:	2011-002093-23
Sponsor's Protocol Code Number:	1.01
National Competent Authority:	Estonia - SAM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2011-09-19
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

Estonia - SAM

A.2

EudraCT number

2011-002093-23

A.3

Full title of the trial

Bioavailability of oral N-acetylcysteine in different intensive care unit patient groups

Suukaudselt manustatud N-atsetüültsüsteiini biosaadavus erineva hospitaliseerimis-näidustusega intensiivravi osakonna patsientidel

A.3.1

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

Absorption of drug N acetylcysteine from gastrointestinal system in severely ill patients

Ravimi atsetüültsüsteiini imendumine väga raskelt haigete patsientide soolestikust

A.3.2

Name or abbreviated title of the trial where available

ACC bioavailability in ICU

A.4.1

Sponsor's protocol code number

1.01

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	University of Tartu
B.1.3.4	Country	Estonia
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	University of Tartu
B.4.2	Country	Estonia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University of Tartu
B.5.2	Functional name of contact point	Juri Karjagin
B.5.3	Address:
B.5.3.1	Street Address	Puusepa 8
B.5.3.2	Town/ city	Tartu
B.5.3.3	Post code	51014
B.5.3.4	Country	Estonia
B.5.4	Telephone number	+3727318380
B.5.5	Fax number	+3727318409
B.5.6	E-mail	juri.karjagin@kliinikum.ee

D. IMP Identification
D.IMP: 1
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.2.1.2	Country which granted the Marketing Authorisation	Estonia
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	N-acetylcysteine
D.3.4	Pharmaceutical form	Dispersible tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Enteral use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ACETYLCYSTEINE
D.3.9.1	CAS number	616-91-1
D.3.9.2	Current sponsor code	1
D.3.9.3	Other descriptive name	NAC
D.3.9.4	EV Substance Code	SUB05229MIG
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	200
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.2.1.2	Country which granted the Marketing Authorisation	Estonia
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	N-acetylcysteine
D.3.4	Pharmaceutical form	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	ACETYLCYSTEINE
D.3.9.1	CAS number	616-91-1
D.3.9.2	Current sponsor code	2
D.3.9.3	Other descriptive name	NAC iv
D.3.9.4	EV Substance Code	SUB05229MIG
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	200
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

Severe neurotrauma, severe pulmonary infections and severe gastrointestinal disease (eg peritonitis, pancreatitis, ileus, major abdominal surgery etc). Need for liquefaction of viscous sputum

E.1.1.1

Medical condition in easily understood language

Severe affections of different organ systems: nervous system, lungs and stomach. Need for sputum liquefaction.

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

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

To measure N acetylcysteine oral bioavailability in different ICU patients: isolated severe neurotrauma, isolated severe lung infection and isolated severe gastrointestinal condition (pancreatitis, peritonitis, major abdominal surgery)

Uurimistöö eesmärk on selgitada N-atsetüültsüsteiini biosaadavus suukaudselt manustatavate ravimpreparaatide korral võrreldes intravenosselt manustatavate ravimpreparaatidega kolmes erinevas intensiivravi patsientide rühmas: isoleeritud neurotraumaga patsiendid, isoleeritud kopsuhaigusega patsiendid ja kõhuõõne haaratusega patsiendid (nt. pankreatiit, kõhuõõne sisene operatsioon)

E.2.2

Secondary objectives of the trial

none

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

adult 18-65 y
N-acetylcysteine indication for sputum liquefaction
Reason for ICU admission (only one): severe neurotrauma, severe lung disease (eg. pneumonia, COPD exacerbation) or severe gastrointestinal disease (eg. pancreatitis, peritonitis, major abdominal surgery)

täiskasvanud vanuses 18-65 eluaastat;
N-atsetüültsüsteiini manustamise näidustus rögalahtistamiseks
intensiivravis viibimise põhjuseks on: isoleeritud ajutrauma või isoleeritud kopsuhaigus (sh kopsupõletik, KOKi ägenemine) või kõhuõõneorganite haigus (sh peritoniit, pankreatiit, ulatuslik kõhukirurgia).

E.4

Principal exclusion criteria

no informed consent from patient or next to kin relative
allergy to N acetylcysteine or durg components
enteral feeding intollerance or enteral feeding is contraindicated
creatinine clearnace lower than 30 ml/min, calculated using Cokcroft-Gault equation
liver dysfunction, defined as increase in AST/ALT more than 2 times reference value and/or hyperbilirubineemia
morbid obesity KMI more then 35 kg/m2

patsiendi või sugulase loobumine uuringus osalemisest;
allergia N-atsetüültsüsteiini või mõne teise ravimi komponendi suhtes;
patsiente, kellel on enteraalse toitmise talumatus või vastunäidustus;
neerufunktsiooni langus (patsiendid, kelle kalkuleeritud kreatiniini kliirens on madalam, kui 30 ml/min; kalkulatsiooni aluseks on Cockroft-Gault’i valem)
maksafunktsiooni häiretega patsiente (AST/ALT kahekordne tõus üle normi, hüperbilirubineemia);
morbiidselt ülekaaluline patsient (kehamassiindeks ≥ 35);

E.5 End points

E.5.1

Primary end point(s)

Bioavailability of oral N-acetylcysteine

Suukaudse N-atsetüültsüsteiini biosaadavus

E.5.1.1

Timepoint(s) of evaluation of this end point

8 hours after administration

8 tundi pärast manustamist

E.5.2

Secondary end point(s)

none

E.5.2.1

Timepoint(s) of evaluation of this end point

none

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

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

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

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

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

60 patients: 20 neurotrauma patients, 20 lung disease patients and 20 gastrointestinal patients

60 patsienti: 20 neurotraumaga, 20 kopsuhaigusega ja 20 gastrointestinaalse haaratusega

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:

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

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

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 2011-09-19.

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Critically ill patients often are unconscious due to condition or analgosedation during mechanical ventilation. Informed consent will be obtained from closest relative

Kriitilises seisundis patsiendid võivad olla teadvuseta, kas seisundi tõttu või analgosedatsiooni kasutamise tõttu. Informeeritud nõusolek võetakse lähisuguslaselt.

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)

It is not to be expected different from normal treatment

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

2011-09-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-05-16

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

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