SPD489 in Combination With an Antidepressant in the Treat... | NCT01435759

NCT01435759

ID	Type	Description	Link
2011-003615-28	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

No data available

No data is available for this block.

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
Antidepressant + SPD489 10 mg	Experimental	Drug: Antidepressant + SPD489 (Lisdexamfetamine dimesylate) 10 mg
Antidepressant + SPD489 30 mg	Experimental	Drug: Antidepressant + SPD489 (Lisdexamfetamine dimesylate) 30 mg
Antidepressant + SPD489 50 mg	Experimental	Drug: Antidepressant + SPD489 (Lisdexamfetamine dimesylate) 50 mg
Antidepressant + SPD489 70 mg	Experimental	Drug: Antidepressant + SPD489 (Lisdexamfetamine dimesylate) 70 mg
Antidepressant + Placebo	Placebo Comparator	Drug: Antidepressant + Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Antidepressant + SPD489 (Lisdexamfetamine dimesylate) 10 mg	Drug	Antidepressant + SPD489 oral, 10 mg, once daily for 8 weeks	Antidepressant + SPD489 10 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in Montgomery-Ǻsberg Depression Rating Scale (MADRS) Total Score From Augmentation Baseline (Week 8) to Week 16 (Double-blind Phase, Dose Response Evaluable Set)	MADRS is a validated, 10-item rating scale with each item being scored on a scale from 0-6 with a total score ranging from 0-60. Lower scores indicate a decreased severity of depression. CHange in MADRS total score in Augmentsion Baseline to Week 16.	Augmentation Baseline (Week 8) to Week 16

Secondary Outcomes

Measure	Description	Time Frame
Change in Average Systolic Blood Pressure From Augmentation Baseline (Week 8) to Week 16		From Augmentation Baseline (Week 8) to Week 16
Change in Average Diastolic Blood Pressure From Augmentation Baseline (Week 8) to Week 16		From Augmentation Baseline (Week 8) to Week 16

Eligibility Module

Eligibility Criteria

Inclusion Criteria

Subject is able to provide written, personally signed and dated informed consent to participate in the study before completing any study-related procedures.
Subject is between 18-65 years of age.
Subject has a primary diagnosis of non-psychotic MDD.
Subject has a MADRS total score 24
Subject is willing and has an understanding and ability to fully comply with study procedures and restrictions defined in this protocol.
Subject, who is female, must have a negative serum beta human chorionic gonadotropin (HCG) pregnancy test and a negative urine pregnancy test and agrees to comply with any applicable contraceptive requirements.
Subject is able to swallow a capsule.

Exclusion Criteria

Subject whose current episode of MDD has not responded to an adequate treatment regimen.
Subject who has a lifetime history of treatment resistant depression, defined as having not responded to adequate treatment with 2 or more treatment regimens.
Subject has a current comorbid psychiatric disorder that is either controlled with medications prohibited in this study or is uncontrolled and associated with significant symptoms.
Subject has been hospitalized (within the last 12 months) for their current MDD episode.
Subject has a current or lifetime history of attention-deficit/hyperactivity disorder (ADHD).
Subject has a first degree relative that has been diagnosed with bipolar I disorder.
Subject has a recent history (within the last 6 months) of suspected substance abuse or dependence disorder.
Subject is considered a suicide risk, has previously made a suicide attempt within the past 3 years, or is currently demonstrating active suicidal ideation.
Subject has a concurrent chronic or acute illness or unstable medical condition.
Subject has a history of seizures (other than infantile febrile seizures), any tic disorder, or a current diagnosis and/or a known family history of Tourette's Disorder, serious neurological disease, history of significant head trauma, dementia, cerebrovascular disease, Parkinson's disease, or intracranial lesions.
Subject has known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant medication.
Subject has a history of thyroid disorder that has not been stabilized on thyroid medication or treatment within 3 months prior to the Screening Visit.
Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
Subject has glaucoma.
Subject has any clinically significant ECG or clinical laboratory abnormalities at the Screening Visit.
Subject has a history of moderate to severe hypertension.
Current use of any other medication (including over-the-counter [OTC], herbal or homeopathic preparations) that has central nervous system effects.
Subject has the potential to need to initiate or modify frequency of psychotherapy or to continue or initiate other treatments for depression, outside of those allowed in this protocol.
Subject has had electroconvulsive therapy for the current depressive episode 3 months prior to the Lead-in Baseline Visit.
The subject has a known or suspected intolerance or hypersensitivity to the investigational product.
The subject has a known or suspected intolerance or hypersensitivity to any of the possible antidepressant treatments (escitalopram oxalate or venlafaxine HCL extended release.
Subject has a positive urine drug result.
Subject has a body mass index of <18.5 or >40.
Subject is female and is pregnant or nursing.
Subject has participated in another clinical study involving SPD489/NRP104 or has previously used commercial lisdexamfetamine dimesylate.

Contacts/Locations Module

Name	Affiliation	Role
Study Director	Takeda	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Arkansas Psychiatric Clinic Clinical Research Trials		Little Rock	Arkansas	72223	United States
South Coast Clinical Trials

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
28857719	Result	Richards C, Iosifescu DV, Mago R, Sarkis E, Reynolds J, Geibel B, Dauphin M. A randomized, double-blind, placebo-controlled, dose-ranging study of lisdexamfetamine dimesylate augmentation for major depressive disorder in adults with inadequate response to antidepressant therapy. J Psychopharmacol. 2017 Sep;31(9):1190-1203. doi: 10.1177/0269881117722998. Epub 2017 Aug 31.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Antidepressant + Single-blind Placebo	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily single-blind placebo (matching SPD489).
FG001	Antidepressant + Double-blind Placebo

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

FG0001197 subjectsOf these 1197 subjects, 19 subjects were not dosed.
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects

Safety Analysis Set: All subjects who took at least 1 dose of randomized investigational product and who had at least 1 post-augmentation baseline safety assessment (e.g. coming back for any visit, reporting of an adverse event [AE] or reporting the absence of AEs). Subjects who received only single-blind placebo were not included in this group.

Arm/Group Information

ID	Title	Description
BG000	Antidepressant + Double-blind Placebo	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily double-blind placebo (matching SPD489).
BG001	Antidepressant + Double-blind SPD489 10mg	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily over-encapsulated SPD489 as a 10mg dose.
BG002	Antidepressant + Double-blind SPD489 30mg	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily over-encapsulated SPD489 as a 30mg dose.
BG003	Antidepressant + Double-blind SPD489 50mg	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily over-encapsulated SPD489 as a 50mg dose.
BG004	Antidepressant + Double-blind SPD489 70mg	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily over-encapsulated SPD489 as a 70mg dose.
BG005	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00043.7± 10.48 BG00139.1± 11.83 BG00243.4± 12.06 BG003

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

18-55

Title	Measurements
	BG00069 BG00170 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00053 BG00153 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

ARGENTINA

Title	Measurements
	BG0002 BG0013 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Secondary

Change in Average Systolic Blood Pressure From Augmentation Baseline (Week 8) to Week 16

Vital Signs Evaluable Set: All randomized subjects who had at least 1 valid vital signs measurement during the Dose Maintenance Period while on the target dose level of investigational product.

Posted

Mean

Standard Deviation

mmHg

From Augmentation Baseline (Week 8) to Week 16

ID	Title	Description
OG000	Antidepressant + Double-blind Placebo	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily double-blind placebo (matching SPD489).
OG001	Antidepressant + Double-blind SPD489 10mg	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily over-encapsulated SPD489 as a 10mg dose.
OG002	Antidepressant + Double-blind SPD489 30mg	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily over-encapsulated SPD489 as a 30mg dose.
OG003	Antidepressant + Double-blind SPD489 50mg	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily over-encapsulated SPD489 as a 50mg dose.
OG004	Antidepressant + Double-blind SPD489 70mg	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily over-encapsulated SPD489 as a 70mg dose.

Units	Counts
Participants	OG00067 OG00168 OG00265 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.2± 9.55 OG0010.2± 8.58 OG0020.5± 9.17 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002 OG003 OG004		MCP-Mod Analysis	The systolic blood pressure p-value was based on a critical value of 1.99 from a multivariate-t distribution with 341 degrees of freedom.	0.004		Least Squares Mean	3.16	Standard Error of the Mean	1.01	2-Sided						The t-statistic used for this analysis, 3.14, was based on MCP-Mod Analysis for the candidate model EMax.		Superiority or Other (legacy)

Secondary

Change in Average Diastolic Blood Pressure From Augmentation Baseline (Week 8) to Week 16

Vital Signs Evaluable Set: All randomized subjects who had at least 1 valid vital signs measurement during the Dose Maintenance Period while on the target dose level of investigational product.

Posted

Mean

Standard Deviation

mmHg

From Augmentation Baseline (Week 8) to Week 16

ID	Title	Description
OG000	Antidepressant + Double-blind Placebo	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily double-blind placebo (matching SPD489).
OG001	Antidepressant + Double-blind SPD489 10mg	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily over-encapsulated SPD489 as a 10mg dose.
OG002	Antidepressant + Double-blind SPD489 30mg	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily over-encapsulated SPD489 as a 30mg dose.

Secondary

Change in Average Pulse Rate From Augmentation Baseline (Week 8) to Week 16

Vital Signs Evaluable Set: All randomized subjects who had at least 1 valid vital signs measurement during the Dose Maintenance Period while on the target dose level of investigational product.

Posted

Mean

Standard Deviation

bpm

From Augmentation Baseline (Week 8) to Week 16

ID	Title	Description
OG000	Antidepressant + Double-blind Placebo	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily double-blind placebo (matching SPD489).
OG001	Antidepressant + Double-blind SPD489 10mg	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily over-encapsulated SPD489 as a 10mg dose.
OG002	Antidepressant + Double-blind SPD489 30mg	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily over-encapsulated SPD489 as a 30mg dose.

Primary

Change in Montgomery-Ǻsberg Depression Rating Scale (MADRS) Total Score From Augmentation Baseline (Week 8) to Week 16 (Double-blind Phase, Dose Response Evaluable Set)

MADRS is a validated, 10-item rating scale with each item being scored on a scale from 0-6 with a total score ranging from 0-60. Lower scores indicate a decreased severity of depression. CHange in MADRS total score in Augmentsion Baseline to Week 16.

Dose Response Evaluable Set (DRES): All randomized subjects who had at least 1 valid primary efficacy measurement (MADRS total score) during the Dose Maintenance Period (Weeks 11-16) while on the target dose level of investigational product.

Posted

Least Squares Mean

90% Confidence Interval

units on a scale

Augmentation Baseline (Week 8) to Week 16

ID	Title	Description
OG000	Antidepressant + Double-blind Placebo	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily double-blind placebo (matching SPD489).
OG001	Antidepressant + Double-blind SPD489 10mg	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily over-encapsulated SPD489 as a 10mg dose.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Antidepressant + Double-blind Placebo	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily double-blind placebo (matching SPD489).	0	78	20	78
EG001	Antidepressant + Double-blind SPD489 10mg	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily over-encapsulated SPD489 as a 10mg dose.	0	77	30	77
EG002	Antidepressant + Double-blind SPD489 30mg	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily over-encapsulated SPD489 as a 30mg dose.	0	76	29	76
EG003	Antidepressant + Double-blind SPD489 50mg	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily over-encapsulated SPD489 as a 50mg dose.	0	78	36	78
EG004	Antidepressant + Double-blind SPD489 70mg	Subjects received unblinded standard antidepressant therapy (either escitalopram oxalate or venlafaxine hydrochloride extended-release titrated to the maximum tolerated dose) plus oral, once daily over-encapsulated SPD489 as a 70mg dose.	1	80	44	80

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Cholecystitis	Hepatobiliary disorders				EG0000 events0 affected78 at risk EG0010 events0 affected77 at risk EG0020 events0 affected76 at risk EG0030 events0 affected78 at risk EG0041 events1 affected80 at risk

Other Adverse Events

Term	Organ System	Statistical Information
Diarrhoea	Gastrointestinal disorders	EG0005 events4 affected78 at risk EG0012 events2 affected77 at risk EG0023 events3 affected76 at risk EG0032 events2 affected78 at risk EG0045 events5 affected80 at risk
Dry mouth	Gastrointestinal disorders	EG0001 events1 affected78 at risk EG0012 events2 affected77 at risk EG0022 events2 affected76 at risk EG003
Nausea	Gastrointestinal disorders	EG0001 events1 affected78 at risk EG0015 events5 affected77 at risk EG0026 events6 affected76 at risk EG003
Fatigue	General disorders	EG0001 events1 affected78 at risk EG0010 events0 affected77 at risk EG0022 events2 affected76 at risk EG003
Influenza	Infections and infestations	EG0003 events2 affected78 at risk EG0011 events1 affected77 at risk EG0024 events4 affected76 at risk EG003
Nasopharyngitis	Infections and infestations	EG0000 events0 affected78 at risk EG0015 events5 affected77 at risk EG0025 events4 affected76 at risk EG003
Upper respiratory tract infection	Infections and infestations	EG0000 events0 affected78 at risk EG0013 events3 affected77 at risk EG0023 events3 affected76 at risk EG003
Urinary tract infection	Infections and infestations	EG0005 events5 affected78 at risk EG0011 events1 affected77 at risk EG0022 events2 affected76 at risk EG003
Blood pressure increased	Investigations	EG0000 events0 affected78 at risk EG0011 events1 affected77 at risk EG0020 events0 affected76 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	EG0001 events1 affected78 at risk EG0014 events4 affected77 at risk EG0026 events5 affected76 at risk EG003
Dizziness	Nervous system disorders	EG0002 events2 affected78 at risk EG0012 events2 affected77 at risk EG0022 events2 affected76 at risk EG003
Headache	Nervous system disorders	EG00012 events10 affected78 at risk EG0018 events7 affected77 at risk EG0029 events5 affected76 at risk EG003
Bruxism	Psychiatric disorders	EG0001 events1 affected78 at risk EG0010 events0 affected77 at risk EG0021 events1 affected76 at risk EG003
Insomnia	Psychiatric disorders	EG0002 events2 affected78 at risk EG0019 events7 affected77 at risk EG0022 events2 affected76 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	EG0001 events1 affected78 at risk EG0014 events4 affected77 at risk EG0020 events0 affected76 at risk EG003

ID	Term
D003865	Depressive Disorder, Major

ID	Term
D000928	Antidepressive Agents
D000069478	Lisdexamfetamine Dimesylate

Ancestor Terms

ID	Term
D011619	Psychotropic Drugs
D002491	Central Nervous System Agents
D045506	Therapeutic Uses
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses
D003913	Dextroamphetamine
D000661	Amphetamine
D000662	Amphetamines
D010627	Phenethylamines
D005021	Ethylamines
D000588	Amines
D009930	Organic Chemicals

EG00410 events10 affected80 at risk

EG0047 events6 affected80 at risk

EG0044 events4 affected80 at risk

EG0041 events1 affected80 at risk

EG0048 events7 affected80 at risk

EG0043 events3 affected80 at risk

EG0042 events2 affected80 at risk

EG0044 events4 affected80 at risk

EG0046 events4 affected80 at risk

EG0041 events1 affected80 at risk

EG0049 events8 affected80 at risk

EG0047 events6 affected80 at risk

EG00411 events9 affected80 at risk

EG0043 events3 affected80 at risk

ID	Term
D003866	Depressive Disorder
D019964	Mood Disorders
D001523	Mental Disorders