Clinical Trials Register

Summary
EudraCT Number:	2010-019925-33
Sponsor's Protocol Code Number:	D4130C00003
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-06-28
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

Czechia - SUKL

A.2

EudraCT number

2010-019925-33

A.3

Full title of the trial

A Multicenter, Randomized, Double-Blind, Parallel Group, Placebo-Controlled, Phase III Efficacy and Safety Study of TC-5214 (S-mecamylamine) in Flexible Doses as an Adjunct to an Antidepressant in Patients with Major Depressive Disorder Who Exhibit an Inadequate Response to Antidepressant Therapy

A.3.1

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

A study to assess the efficacy and safety of TC-5214 as an adjunct therapy in patients with major depressive disorder

A.4.1

Sponsor's protocol code number

D4130C00003

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01180400

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	AstraZeneca AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AstraZeneca AB
B.4.2	Country	Sweden
B.4.1	Name of organisation providing support	Targacept, Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca
B.5.2	Functional name of contact point	Information Centre
B.5.4	Telephone number	001 800 236 9933
B.5.6	E-mail	information.center@astrazeneca.com

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	No
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	TC-5214 (S-mecamylamine)
D.3.2	Product code	TC-5214 (S-mecamylamine)
D.3.4	Pharmaceutical form	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.3.9.1	CAS number	107596-30-5
D.3.9.2	Current sponsor code	TC-5214-23
D.3.9.3	Other descriptive name	S(+)-Mecamylamine
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	1
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	No
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	TC-5214 (S-mecamylamine)
D.3.2	Product code	TC-5214 (S-mecamylamine)
D.3.4	Pharmaceutical form	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.3.9.1	CAS number	107596-30-5
D.3.9.2	Current sponsor code	TC-5214-23
D.3.9.3	Other descriptive name	S(+)-Mecamylamine
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	2
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: 3
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	No
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	TC-5214 (S-mecamylamine)
D.3.2	Product code	TC-5214 (S-mecamylamine)
D.3.4	Pharmaceutical form	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.3.9.1	CAS number	107596-30-5
D.3.9.2	Current sponsor code	TC-5214-23
D.3.9.3	Other descriptive name	S(+)-Mecamylamine
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	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	Tablet
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

Adjunct treatment to an antidepressant in patients with Major Depressive Disorder who exhibit an inadequate response to antidepressant therapy

E.1.1.1

Medical condition in easily understood language

Mental disorder characterized by an all-encompassing low mood
accompanied by low self-esteem, and by loss of interest or pleasure in
normally enjoyable activities.

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	13.1
E.1.2	Level	PT
E.1.2	Classification code	10057840
E.1.2	Term	Major depression
E.1.2	System Organ Class	10037175 - Psychiatric disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	13.1
E.1.2	Level	LLT
E.1.2	Classification code	10025453
E.1.2	Term	Major depressive disorder NOS
E.1.2	System Organ Class	10037175 - Psychiatric disorders

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 evaluate the efficacy of TC-5214 compared with placebo as an adjunct to antidepressant (selective serotonin reuptake inhibitor [SSRI]/serotonin/norepinephrine reuptake inhibitor [SNRI]) therapy in patients with major depressive disorder (MDD) who exhibit an inadequate response to antidepressant therapy, as assessed by change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from randomization (Week 8) to end of treatment (Week 16).

Safety objectives:
To evaluate the safety and tolerability of TC-5214 and placebo as an adjunct to an
antidepressant (SSRI/SNRI) in patients with MDD who exhibit an inadequate response to antidepressant therapy.

E.2.2

Secondary objectives of the trial

To evaluate the efficacy of TC-5214 compared with placebo as an adjunct to an antidepressant (SSRI/SNRI) in patients with MDD who exhibit an inadequate response to antidepressant therapy as assessed by depressive symptoms, clinical global outcome regarding severity and improvement and anxiety, and also as assessed by patient-reported outcomes (PROs) regarding functional impairment and overall quality of life and severity of depressive symptoms.

To investigate pharmacokinetic (PK) properties of TC-5214 in patients with MDD using a population PK analysis methodology. These results will be reported separately from the primary and other secondary objectives.

Change in overall quality of life and satisfaction from randomization (Week 8) to end of treatment (Week 16) in Q-LES-Q-SF, items 15 and 16

Change in health-related quality of life as measured by the EuroQol VAS and 5 dimensions (EQ-5D) from randomization (Week 8) to end of treatment (Week 16)

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Pharmacogenetics Research, appendix version 1.0, dated 23 March 2011

AstraZeneca intends to perform genetic research in the TC-5214 clinical development
program to explore how genetic variations may affect the clinical parameters associated with TC-5214 and/or agents used in combination or as comparators. Collection of DNA samples from populations with well described clinical characteristics may lead to improvements in the design and interpretation of clinical trials and, possibly, to genetically guided treatment strategies. Studies may also be performed on the underlying genetic contribution to MDD.
The objective of this research is to collect and store DNA for future exploratory research into genes/genetic variation that may influence response (ie, distribution, safety, tolerability and efficacy) to TC-5214 and/or co-medication. Investigations into the genetic factors influencing disease (depression) may also be undertaken.

E.3

Principal inclusion criteria

Provision of signed and dated informed consent before initiation of any study-related procedures.

The patient must have a clinical diagnosis of major depressive disorder (MDD) with inadequate response to no more than one antidepressant.

Out-patient status at enrollment and randomization.

E.4

Principal exclusion criteria

Patients with a lifetime history of bipolar disorder, psychotic disorder or post-traumatic stress disorder.

Patients with a history of suicide attempts in the past year and/or seen by the investigator as having a signficant history of risk of suicide or homicide.

History of renal insufficiency or impairment or conditions that could affect absorption or metabilism of the investigationl product in this patient population

E.5 End points

E.5.1

Primary end point(s)

Primary efficacy variable: Change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from randomization (Week 8) to end of treatment (Week 16)

E.5.1.1

Timepoint(s) of evaluation of this end point

Will be scored at Weeks 8 (baseline), 9, 10, 12, 14 and 16.

E.5.2

Secondary end point(s)

Changes in clinician-rated symptoms as assessed by MADRS, HAM-D, CGI-S, and CGI-I

Changes in patient-reported outcomes as assessed by SDS and Q-LES-Q-SF

AEs, SAEs, change in physical exam results and vital signs, laboratory tests and ECG, C-SSRS, BARS and AIMS, CSFQ, and DESS will be assessed as a measure of safety and tolerability

E.5.2.1

Timepoint(s) of evaluation of this end point

MADRS and CGI will be scored at Weeks 8 (baseline), 9, 10, 12, 14 and 16; HAM-D will be scored at Weeks 8 (baseline) and 16

Will be analysed at Weeks 8, 12 and 16 for SDS and Weeks 8 and 16 for Q-LES-Q-SF

Time consent signed (enrollment, 2 wk screening/washout period), during 8-wk prospective open-label period, during 8-wk randomized double-blind period, and during 2-wk follow up period. Unsolicited SAEs collected 30 days post last treatment

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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

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)

Yes

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

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

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

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

The end of the study is defined as “the last visit of the last patient undergoing the study”. The end of study definition is for the entire study.

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.2.1	Number of subjects for this age range:	893
F.1.3	Elderly (>=65 years)	No
F.1.3.1	Number of subjects for this age range:	47
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
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 2010-06-28.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	44
F.4.2	For a multinational trial
F.4.2.1	In the EEA	940
F.4.2.2	In the whole clinical trial	940

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

2010-10-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-06-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-09-27

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