Clinical Trials Register

Summary
EudraCT Number:	2011-003019-47
Sponsor's Protocol Code Number:	SPD489-329
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2013-02-12
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

UK - MHRA

A.2

EudraCT number

2011-003019-47

A.3

Full title of the trial

A Phase 3, Open-label, Multicenter, 12-month Extension Safety and Tolerability Study of SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder With Residual Symptoms or Inadequate Response Following Treatment With an Antidepressant.

A.3.1

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

A study to examine the study drug, SPD489, in subjects with major depressive disorder (MDD) who are taking certain types of antidepressants and continuing to have MDD symptoms.

A.3.2

Name or abbreviated title of the trial where available

SPD489-329

A.4.1

Sponsor's protocol code number

SPD489-329

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01436175

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	Shire Development Inc.
B.1.3.4	Country	United States
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	Shire Development 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	Shire Pharmaceuticals Ltd
B.5.2	Functional name of contact point	Medical Communications
B.5.3	Address:
B.5.3.1	Street Address	Hampshire International Business Park
B.5.3.2	Town/ city	Chineham, Basingstoke, Hampshire
B.5.3.3	Post code	RG24 8EP
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+440800 0556614
B.5.5	Fax number	+4401256894714
B.5.6	E-mail	medinfoglobal@shire.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	Yes
D.2.1.1.1	Trade name	Vyvanse
D.2.1.1.2	Name of the Marketing Authorisation holder	Shire US Inc
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Lisdexamfetamine dimesylate (LDX)
D.3.2	Product code	SPD489
D.3.4	Pharmaceutical form	Capsule, hard
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	Lisdexamfetamine dimesylate
D.3.9.1	CAS number	608137-33-3
D.3.9.2	Current sponsor code	SPD489
D.3.9.3	Other descriptive name	NRP104
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.3.11 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.2.1.1.1	Trade name	Vyvanse
D.2.1.1.2	Name of the Marketing Authorisation holder	Shire US Inc
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Lisdexamfetamine dimesylate (LDX)
D.3.2	Product code	SPD489
D.3.4	Pharmaceutical form	Capsule, hard
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	Lisdexamfetamine dimesylate
D.3.9.1	CAS number	608137-33-3
D.3.9.2	Current sponsor code	SPD489
D.3.9.3	Other descriptive name	NRP104
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.3.11 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	Yes
D.2.1.1.1	Trade name	Vyvanse
D.2.1.1.2	Name of the Marketing Authorisation holder	Shire US Inc
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Lisdexamfetamine dimesylate (LDX)
D.3.2	Product code	SPD489
D.3.4	Pharmaceutical form	Capsule, hard
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	Lisdexamfetamine dimesylate
D.3.9.1	CAS number	608137-33-3
D.3.9.2	Current sponsor code	SPD489
D.3.9.3	Other descriptive name	NRP104
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)	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: 4
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	Vyvanse
D.2.1.1.2	Name of the Marketing Authorisation holder	Shire US Inc
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Lisdexamfetamine dimesylate (LDX)
D.3.2	Product code	SPD489
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use Route of administration not applicable
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Lisdexamfetamine dimesylate
D.3.9.1	CAS number	608137-33-3
D.3.9.2	Current sponsor code	SPD489
D.3.9.3	Other descriptive name	NRP104
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	70
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

Major Depressive Disorder

E.1.1.1

Medical condition in easily understood language

Depression

E.1.1.2

Therapeutic area

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

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

The primary objective is to evaluate the long-term safety and tolerability of SPD489 administered as a daily morning dose (20, 30, 50, and 70mg/day) as adjunctive therapy to an antidepressant for the treatment of major depressive disorder (MDD) in adults (18-65 years of age inclusive at the time of consent for the respective short-term antecedent SPD489 MDD study). Long-term safety will be described using:
• Occurrence of treatment-emergent adverse events (TEAEs),
• Responses to the Columbia Suicide Severity Rating Scale (C-SSRS), and
• Specific evaluation of blood pressure and pulse rate, clinical laboratory evaluations, and electrocardiogram (ECG) results.

E.2.2

Secondary objectives of the trial

To evaluate the effect of SPD489 on perception of health, quality of life, resource utilization, sexual functioning, depression symptoms, depression improvement, and amphetamine withdrawal symptoms.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

· Subject has completed 1 of the respective short-term antecedent SPD489 MDD studies and did not experience any clinically significant adverse events in the antecedent study that would preclude exposure to SPD489.

Subject was randomized as an inadequate responder in the antecedent study, or not randomized but continues to demonstrate residual depressive symptoms (MADRS total score of ≥5) at the end of the antecedent study, and in the Investigator’s opinion has the potential to benefit from adjunctive pharmacologic treatment.

E.4

Principal exclusion criteria

Subject is considered a suicide risk in the opinion of the Investigator, has previously made a suicide attempt within the past 3 years, or is currently demonstrating active suicidal ideation.

Subject has any current co-morbid psychiatric disorder, either controlled with medications prohibited in this study or uncontrolled and associated with significant symptoms, which was not present or recognized at entry into the antecedent study and would have been exclusionary in the antecedent study.

A new onset or known history of serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant medication, a history of moderate to severe hypertension or an average (of 3 readings) resting sitting systolic blood pressure >139mmHg or an average (of 3 readings) diastolic blood pressure >89mmHg at study entry, or has a concurrent chronic or acute illness or unstable medical condition that may deteriorate that could confound the results of safety assessments, increase risk to the subject, or lead to difficulty complying with the protocol.

E.5 End points

E.5.1

Primary end point(s)

Safety and tolerability as assessed by the occurrence of treatment emergent adverse events (TEAEs), response to the Columbia-Suicide Severity Rating Scale (C-SSRS), and specific evaluation of blood pressure and pulse rate, clinical laboratory evaluations, and electrocardiogram (ECG) results.

E.5.1.1

Timepoint(s) of evaluation of this end point

• TEAE: Week1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Any, 53/Any
• C-SSRS: Week 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Any, 53/Any
• BP and Pulse: Week 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Any, 53/Any
• Clinical labs: Week 0, 24, and 52/Any
• ECG: Week 0, 12, 24, 36, 48, 52/Any

E.5.2

Secondary end point(s)

1) Change from the Augmentation Baseline Visit of the antecedent study (Visit 8 [Week 8]) in the Sheehan Disabillity Scale (SDS) total score.
2) Change from the Augmentation Baseline Visit of the antecedent study (Visit 8 [Week 8]) in the Change in Clinical Global Impressions - Global Improvement (CGI-I)
3) Change from the Augmentation Baseline Visit of the antecedent study (Visit 8 [Week 8]) in the Quick Inventory of Depressive Symptomatology - Self Report (QIDS SR)
4) Change from the Augmentation Baseline Visit of the antecedent study (Visit 8 [Week 8]) in the Short Form-12 Health Survey V2 (SF-12V2)
5) Change from the Augmentation Baseline Visit of the antecedent study (Visit 8 [Week 8]) in the EuroQoL Group 5-Dimension Self-Report Questionnaire (EQ-5D-5L index score)
6) Change from the Augmentation Baseline Visit of the antecedent study (Visit 8 [Week 8]) in the Quality of Life Enjoyment Satisfaction Questionnaire Short Form (QLES-Q-SF)
7) Change from the Augmentation Baseline Visit of the antecedent study (Visit 8 [Week 8]) to Visit 16 (Week 52/Any) in the Changes in Sexual Functioning Questionnaire – 14-item scale (CSFQ-14)
8) Change in the Patient Resource Utilization Questionnaire (PRUQ)
9) Amphetamine Cessation Symptom Assessment (ACSA)

E.5.2.1

Timepoint(s) of evaluation of this end point

1) Week: 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Any
2+3+6) Week 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Any
4+5) Week: 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Any
7+8) Week 0, 12, 24, 36, 48, 52/Any
9) Week: 53/Any

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

Yes

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

Yes

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability, amphetamine withdrawal

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

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Australia

Belgium

Canada

Chile

Croatia

Czech Republic

Estonia

Finland

France

Germany

Hungary

Italy

Mexico

Poland

Romania

South Africa

Spain

Sweden

United Kingdom

United States

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

Last subject last visit

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:

1665

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

291

F.4.2.2

In the whole clinical trial

1700

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)

Subjects will revert to their treatments pre-study.

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

2013-03-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-12-21

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2014-02-10

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