Clinical Trials Register

Summary
EudraCT Number:	2012-004483-22
Sponsor's Protocol Code Number:	35664
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-02-19
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

Denmark - DHMA

A.2

EudraCT number

2012-004483-22

A.3

Full title of the trial

NACOS - The effect of N-acetylcystein for depressive symptoms in patients with bipolar depression - A double blind randomized placebo-controlled trial with follow up

NACOS - Effekten af N-acetylcystein på de depressive symptomer hos patienter med bipolar depression – Et dobbelt blindet randomiseret placebo kontrolleret forsøg med follow-up

A.3.1

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

NACOS - Effect of novel treatment for depressive symptoms in patients with bipolar depression - A double blind randomized placebo-controlled trial with follow up

NACOS - Effekten af en ny behandling på de depressive symptomer hos patienter der er manio-depressive - Et dobbelt blindet randomiseret placebo kontrolleret forsøg med opfølgning

A.3.2

Name or abbreviated title of the trial where available

NACOS

A.4.1

Sponsor's protocol code number

35664

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	Mental Health Service, Esbjerg
B.1.3.4	Country	Denmark
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	Mental Health Service, Esbjerg
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Mental Health Service, Esbjerg
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	Østergade 12
B.5.3.2	Town/ city	Esbjerg
B.5.3.3	Post code	6700
B.5.3.4	Country	Denmark
B.5.4	Telephone number	4551717423
B.5.6	E-mail	Connie.Thuroee.Nielsen@rsyd.dk

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.2.1.1.1	Trade name	Mucolysin, mucomyst, Granon
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	NAC
D.3.2	Product code	R05CB01
D.3.4	Pharmaceutical form	Capsule
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	N-acetylcystin
D.3.9.1	CAS number	7218-04-4
D.3.9.3	Other descriptive name	S-1,2-DICHLOROVINYL-N-ACETYLCYSTEINE
D.3.9.4	EV Substance Code	SUB125190
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	500
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Bipolar depression

E.1.1.1

Medical condition in easily understood language

Depression symptoms and mood among patientes with the mental disorder bipolar affective disorder or manic-depressive illness, which is equivalent to episodes of serious mood swings.

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10004936
E.1.2	Term	Bipolar depression
E.1.2	System Organ Class	100000004873

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The aim of the study is to identify the effect of NAC on the depressive symptoms in patients with bipolar depression

Formålet er, at påvise effekten af NAC ved måling af de depressive symptomer hos patienter med bipolar depression

E.2.2

Secondary objectives of the trial

The secondary outcom is to measure the level of oxidative stress, quality of life and level of function.

De sekundære outcomes er målinger af niveauet af det oxidative stress, livskvalitet og funktionsniveau.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients that meet the DSM-5 criteria of bipolar disorder type 1 or 2 (296-41-296.56 or 296.89) with at least one documented illness episode in the past six months, have had depressive symptoms at least 4 weeks before inclusion, MADRS ≥ 18 at baseline, have been sick at least 4 weeks, between 18-64 years, fertile women with a negative pregnant test at baseline, turtle women using safe contraception in the study period, and patients who have given informed consent.

Patienter der opfylder DSM-5 kriterierne for bipolar lidelse type 1 eller 2 (296-41-296.56 eller 296.89) med mindst én dokumenteret sygdomsperiode i de seneste seks måneder, har haft depressive symptomer i mindst 4 uger op til inklusion, MADRS score ≥ 18 ved baseline (lettere depression), mellem 18-64 år, fertile kvinder som har afleveret en negativ graviditetstest ved indgangen i studiet, samt at de fertile kvinder anvender sikker antikonception under hele forsøgsperioden, og patienter som har afgivet informeret samtykke.

E.4

Principal exclusion criteria

Pregnant women, patients wishing pregnancy during the frame of the
study, current suicidal thoughts, patients that have an intake of more than 500 mg NAC, 200 μm selenium, eller 500 IU of vitamin E every day is excluded. Patients who are hypersensitive to histamin, snf patients who have had ECT-treatment within the last 4 weeks, or have had medication change within the last 4 weeks. Patients with recent bleeding in respiratory, asthma, epilepsi or allergy towards NAC. People who cannot speak or understand the Danish language, or have not give or withdrawn informed consent. If patients change diagnosis during the study, and the primary diagnosis is not bipolar affective disorder is the participant excluded.

Gravide, patienter der ønsker graviditet i løbet af forsøgsperioden, ammende kvinder, aktuelle selvmordsovervejelser, patienter der indtaget mere end 500 mg NAC, 200 μm selenium, eller 500 IU vitamin E dagligt skal ekskluderes. Patienter der er overfølsomme overfor histamin, eller har fået ECT-behandling i løbet af de sidste 4 uger, eller har haft medicinændringer i løbet af de sidste 4 uger. Patienter med en kendt eller suspekt klinisk relevant systemisk medicinsk sygdom/lidelse, inklusiv astma, bronkospasmer, insufficient respiration, nylig blødning i luftveje, epilepsi eller allergi overfor NAC. Patienter der ikke kan beherske det danske sprog, eller som ikke har afgivet, eller tilbagetrækker den informeret samtykke skal også ekskluderes. Hvis patienten skifter diagnose under forløbet og primær diagnose ikke længere er bipolar affektiv sindslidelse ekskluderes forsøgspersonen ligeledes.

E.5 End points

E.5.1

Primary end point(s)

The total score of MADRS

Den totale score på MADRS

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline, 2, 10, 20 and 24 weeks

Baseline, 2, 10, 20 and 24 uger

E.5.2

Secondary end point(s)

Score of MES, SF-12, GAF-S, GAF-F, CGI-S, YMRS and measurement of oxidativ stress in biological material (urine)

Score af MES, SF-12, GAF-S, GAF-F, CGI-S, YMRS og mållig af oxidativ stress via biologisk materiale (urin)

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline, 2, 10, 20 and 24 weeks

Baseline, 2, 10, 20 and 24 uger

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

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)

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Follow-up

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

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

Yes

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

Good Clinical Practice Unit, Odense University Hospital

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

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

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)

No study treatment

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Forskningsenheden, Psykiatrisk Afdeling Esbjerg
G.4.3.4	Network Country	Denmark
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	Forskningsenheden, Psykiatrisk Afdeling Aalborg
G.4.3.4	Network Country	Denmark
G.4 Investigator Network to be involved in the Trial: 3
G.4.1	Name of Organisation	Psykiatrisk Afdeling Vejle-Kolding-Fredericia
G.4.3.4	Network Country	Denmark
G.4 Investigator Network to be involved in the Trial: 4
G.4.1	Name of Organisation	Affektiv Team Odense
G.4.3.4	Network Country	Denmark

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-11-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-02-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-10-20

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