Clinical Trials Register

Summary
EudraCT Number:	2009-011990-34
Sponsor's Protocol Code Number:	AFX02
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-11-11
Trial results	View 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

Germany - BfArM

A.2

EudraCT number

2009-011990-34

A.3

Full title of the trial

Cytokines and Inflammatory Marker during Therapy in Major Depression with Celecoxib

A.3.2

Name or abbreviated title of the trial where available

CITICOX

A.4.1

Sponsor's protocol code number

AFX02

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Clinic for Psychiatry and Psychotherapy of the Ludwig Maximilian University
B.1.3.4	Country	Germany
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Celebrex
D.2.1.1.2	Name of the Marketing Authorisation holder	Pharmacia Limited
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.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Celecoxib
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	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	Sertraline
D.3.4	Pharmaceutical form	Coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Sertraline
D.3.9.1	CAS number	79617-96-2
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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, hard
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

Major Depression

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 prove or disapprove the hypothesis that an initially raised monocyte COX-2 (PGE-2) expression, the RNA monocyte signature expression, and the serum tryptophan/kynurenine ratio identify a subgroup of patients clinically responding better to add-on COX-2 inhibitor treatment in terms of improvement of the HamD-17 score.

E.2.2

Secondary objectives of the trial

1) Changes from baseline to endpoint (week 6) in HamD-17 score.
2) Changes from baseline to endpoint (week 6) in Montgomery Asberg Depression Rating Scale (MADRS) score.
3) To prove or disapprove the hypothesis that a rapid decline of initially raised RNA monocyte signature or the serum tryptophan/kynurenine ratio during COX-2 inhibitor treatment identifies a subgroup of patients clinically responding better to add-on COX-2 inhibitor treatment in terms of improvement of the HamD-17 score.
4) In an exploratory design, serum levels of CRP, IL-1, IL-1Ra, IL-6, IL-17, TNF-α, TNF-R1, TNF-R2, MIF, TGF-ß, and neuroactive kynurenine metabolites will be followed up during therapy.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Major depression diagnosed by psychiatrist
2) DSM IV TR: 296.2x single depressive episode or 296.3x recurrent depressive episode
3) HamD-17 score ≥ 22
4) Informed consent
5) Age between 18 and 60 years

E.4

Principal exclusion criteria

1) Psychotic depression or bipolar disorder, drug or alcohol addiction, schizoaffective disorders, schizophrenia. Other disorders (e.g. obsessive compulsive disorder, anxiety disorder, personality disorder) in case the symptoms predominate the clinical picture.
2) Unsuccessful treatment with more than 2 antidepressant medications (at therapeutically adequate doses and duration) during current episode.
3) Concomitant use of psychotropic drugs, including mood stabilizers, besides defined co-medication.
4) Immediate risk for suicidal behavior (3 on HamD-17 rating scale or 5 on MAD Rating Scale).
5) Women who are pregnant, breast feeding or planning to become pregnant during the course of study.
6) Women who are not post-menopausal (no natural menopause established in retrospect after 12 consecutive months of amenorrhea without hormone replacement therapy during the last 5 months), surgically sterilized or using a highly effective method of contraception (an implanted or injected hormonal contraceptive, some intrauterine contraceptive devices (IUDs) containing hormones, sexual abstinence, or have a vasectomized partner). Females using combined oral contraceptives should use a different or additional highly effective method of contraception as listed above.
7) Any history of cardiovascular disease (e.g. angina, heart attack, stroke, congestive heart failure), uncontrolled high blood pressure, documented peripheral arterial insufficiency and symptomatic, clinically significant claudication, a history of peripheral arterial embolism or cerebrovascular disease.
8) Patients at risk of QT/QTc interval prolongation (QTc> 450 ms, family history of long QT syndrome or use of medication prolonging QT/QTc interval).
9) History of coronary heart disease (CHD) or any other heart disease.
10) Serum NTproBNP ≥ 125 pg/mL indicating (sub-) clinical heart failure.
11) History of upper or lower gastrointestinal (GI) ulceration, perforation and/or obstruction.
12) History of upper or lower GI bleeding within the previous year.
13) History of inflammatory bowel disease.
14) Undergoing cancer chemotherapy.
15) Known HIV infection or clinically manifest Acquired Immune Deficiency Syndrome (AIDS), diabetes, asthma, COPD, Parkinson’s or Alzheimer’s disease, or any other serious condition likely to interfere with the conduct of the trial.
16) Clinically relevant hepatic or renal impairment (serum albumin < 25 g/L or Child-Pugh > 10 or renal GFR < 30 mL/min), or other clinically significant physical findings or clinically significant laboratory results at screening or baseline, as determined by the investigator.
17) History of allergy to sertraline, celecoxib, sulfonamides or closely related compounds, or excipients.
18) History of hypersensitivity or intolerance to pain medications.
19) Use of pain medication, such as a COX-2 inhibitor, NSAID (non-steroidal anti-inflammatory drug, including aspirin) or acetaminophen (syn. paracetamol) within 72 hours prior to study entry (24 hours for short-acting drugs such as aspirin or acetaminophen).
20) Patients currently taking warfarin.
21) Participation in a study of an investigational drug or device concomitantly or within 30 days prior to this study.
22) Patients thought to be unreliable or incapable of complying with the requirements of the protocol.
23) Treatment with monoamino oxidase inhibitors during the last 14 days or treatment with fluoxetine during the last 6 weeks.

E.5 End points

E.5.1

Primary end point(s)

Peripheral monocyte COX-2 (PGE-2) expression, the RNA monocyte signature and the serum ratio of tryptophan/kynurenine will be measured.
The HamD-17 rating scale score and the Montgomery Asperg Depression Rating Scale score will be determined by investigators who will be trained in the use of these rating scales.
The safety assessments include standard parameters (adverse events, clinical laboratory tests and vital signs) as well as additional cardiovascular safety assessment (at screening) in view of the known class effects of COX-2 inhibitors. Patients with coronary heart disease (CHD) or any other heart disease will be excluded from the study.

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

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Correlation of monocyte COX-2 (PGE-2) expression with clinical response

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

add-on to standart therapy

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.8.3

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

Information not present in EudraCT

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

Follow-up visit of last patient

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.1.3

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.4.2

For a multinational trial

F.4.2.1

In the EEA

128

F.4.2.2

In the whole clinical trial

128

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)

Even if the study medication was identified as beneficial in the study, it can not be provided to the patients since
further studies investigating the efficacy of the medication in major depression are necessary. There is no studyspecific
provision of further treatment and additional medical care of the patients once their participation in
the trial has ended. Afterwards the patient will be treated with the antidepressant prescribed by his/her general
practitioner.

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

2011-01-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-09-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-10-18

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