Efficacy and Safety Study of SPD489 in Combination With a... | NCT01436149

ID	Type	Description	Link
2011-003018-17	EudraCT Number

Status Module

Description Module

Label	Type	Description	Intervention Names
Antidepressant + SPD489	Experimental		Drug: SPD489 (Lisdexamfetamine dimesylate )
Antidepressant + Placebo	Placebo Comparator		Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
SPD489 (Lisdexamfetamine dimesylate )	Drug	Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release or duloxetine hydrochloride) oral, once daily + SPD489 (oral, 20, 30, 50 or 70 mg, once daily) for 8 weeks

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mean Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at up to 8 Weeks	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.	8 weeks

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at up to 8 Weeks	Designed to evaluate the extent to which illness symptoms impact a subject's life in 3 areas: work/school, social, and family/home. Each area is scored on a scale from 0 (no impairment) to 10 (highly impaired) with a total score ranging from 0 (unimpaired) to 30 (highly impaired). Lower scores translate into less impairment.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subject is able to provide written, personally signed, and dated informed consent to participate in the study.
Subject is between 18 and 65 years of age.
Subject has a primary diagnosis of non-psychotic MDD (single or recurrent).
Subject has a MADRS total score 24.
Subject who is female, must have a negative serum beta human chorionic gonadotropin (HCG) pregnancy test and a negative urine pregnancy test at the and agrees to comply with any applicable contraceptive requirements of the protocol.
Subject is able to swallow a capsule.

Exclusion Criteria:

Subject whose current episode of MDD has not responded to an adequate treatment regimen with 2 or more approved single antidepressant agents.
Subject who has a lifetime history of treatment resistant depression.
Subject has a current co-morbid psychiatric disorder. Excluded are: any significant Axis II disorder (including borderline personality disorder), any bipolar disorder, any current or lifetime psychosis, post traumatic stress disorder, obsessive compulsive disorder, any pervasive development disorder, anorexia nervosa and bulimia nervosa.
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 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 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.
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 a history of moderate to severe hypertension.
Current use of any other medications (including over-the-counter [OTC], herbal or homeopathic preparations) that have central nervous system effects.
Subject has had electroconvulsive therapy (ECT) for the current depressive episode 3 months prior.
The subject has a known or suspected intolerance, hypersensitivity, or contraindications to their assigned antidepressant treatments (escitalopram oxalate, sertraline HCl, venlafaxine HCl extended release, or duloxetine HCl).
Subject has a positive urine drug result.
Subject has a body mass index (BMI) of <18.5 or >40.
Subject is female and is pregnant or nursing.

Name	Affiliation	Role
Study Director	Takeda	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Birmingham Research Group		Birmingham	Alabama	35216	United States
AV Institue, Inc.

PubMed Identifier	Type	Citation	Retractions
27474961	Result	Richards C, McIntyre RS, Weisler R, Sambunaris A, Brawman-Mintzer O, Gao J, Geibel B, Dauphin M, Madhoo M. Lisdexamfetamine dimesylate augmentation for adults with major depressive disorder and inadequate response to antidepressant monotherapy: Results from 2 phase 3, multicenter, randomized, double-blind, placebo-controlled studies. J Affect Disord. 2016 Dec;206:151-160. doi: 10.1016/j.jad.2016.07.006. Epub 2016 Jul 5.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Antidepressant + Single-blind Placebo	Subjects received unblinded oral, once daily standard antidepressant therapy (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended-release, or duloxetine hydrochloride) plus oral, once daily placebo (matching SPD489).
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Antidepressant + Double-blind Placebo	Oral, once daily antidepressant therapy (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) plus oral, once daily, double-blind placebo (matching SPD489) for 8 weeks.
BG001	Antidepressant + Double-blind SPD489	Oral, once daily antidepressant therapy (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) plus oral, once daily SPD489 (Lisdexamfetamine dimesylate optimized among 20, 30, 50, or 70 mg dose) for 8 weeks.
BG002	Total	Total of all reporting groups

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

Primary

Mean Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at up to 8 Weeks

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.

Full Analysis Set: Subjects who took at least 1 dose of randomized investigational product and who had at least 1 valid primary efficacy measurement of the MADRS total score after the Augmentation Baseline Visit (Visit 8).

Posted

Least Squares Mean

95% Confidence Interval

units on a scale

8 weeks

ID	Title	Description
OG000	Antidepressant + Placebo	Antidepressant + Placebo: Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + Placebo (oral, once daily) for 8 weeks.
OG001	Antidepressant + SPD489	Antidepressant + SPD489 (Lisdexamfetamine dimesylate): Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + SPD489 (optimized as a 20, 30, 50, or 70 mg dose, oral, once daily), for 8 weeks.

Units	Counts
Participants	OG000200 OG001200

Title

Denominators

Categories

Title	Measurements
	OG000-6.3(-7.6 to -4.9) OG001-6.1(-7.5 to -4.8)

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		Mixed- effects Model for Repeat Measures		0.883		Difference in LS Mean	0.1	Standard Error of the Mean	0.96	2-Sided	95	-1.7	2.0					Superiority or Other (legacy)

Secondary

Change From Baseline in Sheehan Disability Scale (SDS) Total Score at up to 8 Weeks

Designed to evaluate the extent to which illness symptoms impact a subject's life in 3 areas: work/school, social, and family/home. Each area is scored on a scale from 0 (no impairment) to 10 (highly impaired) with a total score ranging from 0 (unimpaired) to 30 (highly impaired). Lower scores translate into less impairment.

Posted

Least Squares Mean

95% Confidence Interval

units on a scale

8 weeks

ID	Title	Description
OG000	Antidepressant + Placebo	Antidepressant + Placebo: Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + Placebo (oral, once daily) for 8 weeks.
OG001	Antidepressant + SPD489	Antidepressant + SPD489 (Lisdexamfetamine dimesylate): Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + SPD489 (optimized as a 20, 30, 50, or 70 mg dose, oral, once daily), for 8 weeks.

Secondary

Percentage of Participants Achieving a 25% Response on the MADRS

The percentage of subjects who achieved a 25% response (i.e., ≥25% reduction in MADRS total score from Lead-in Baseline, Visit 2; Week 0). A comparison was performed at Visit 14/Early Termination (ET) (Week 16/ET).

Posted

Number

percentage of participants

up to 8 weeks

ID	Title	Description
OG000	Antidepressant + Placebo	Antidepressant + Placebo: Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + Placebo (oral, once daily) for 8 weeks.
OG001	Antidepressant + SPD489	Antidepressant + SPD489 (Lisdexamfetamine dimesylate): Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + SPD489 (optimized as a 20, 30, 50, or 70 mg dose, oral, once daily), for 8 weeks.

Units	Counts

Secondary

Percentage of Participants Achieving a 50% Response on the MADRS

The percentage of subjects who achieved a 50% response (i.e., ≥50% reduction in MADRS total score from Lead-in Baseline, Visit 2; Week 0). A comparison was performed at Visit 14/ET (Week 16/ET).

Posted

Number

percentage of participants

up to 8 weeks

ID	Title	Description
OG000	Antidepressant + Placebo	Antidepressant + Placebo: Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + Placebo (oral, once daily) for 8 weeks.
OG001	Antidepressant + SPD489	Antidepressant + SPD489 (Lisdexamfetamine dimesylate): Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + SPD489 (optimized as a 20, 30, 50, or 70 mg dose, oral, once daily), for 8 weeks.

Units	Counts

Secondary

Percentage of Participants Achieving Remission on the MADRS

MADRS remission was defined as a MADRS total score of ≤10. A comparison was performed at Visit 14/ET (Week 16/ET).

Posted

Number

percentage of participants

up to 8 weeks

ID	Title	Description
OG000	Antidepressant + Placebo	Antidepressant + Placebo: Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + Placebo (oral, once daily) for 8 weeks.
OG001	Antidepressant + SPD489	Antidepressant + SPD489 (Lisdexamfetamine dimesylate): Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + SPD489 (optimized as a 20, 30, 50, or 70 mg dose, oral, once daily), for 8 weeks.

Units	Counts
Participants

Secondary

Mean Change From Baseline Over Time in MADRS Total Score

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.

Posted

Least Squares Mean

95% Confidence Interval

units on a scale

Baseline and up to 8 weeks

ID	Title	Description
OG000	Antidepressant + Placebo	Antidepressant + Placebo: Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + Placebo (oral, once daily) for 8 weeks.
OG001	Antidepressant + SPD489	Antidepressant + SPD489 (Lisdexamfetamine dimesylate): Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + SPD489 (optimized as a 20, 30, 50, or 70 mg dose, oral, once daily), for 8 weeks.

Units

Secondary

Mean Change From Baseline in the Quick Inventory of Depressive Symptomatology - Self Report (QIDS SR)

The QIDS-SR is a self-administered questionnaire designed to rate depressive symptoms. The scale contains 16 items, each scored using a 4-point scale ranging from 0 (representing the most favorable response [low amount of symptom]) to 3 (representing the least favorable response [frequent/intense symptom]). The total score could range from 0 (no depression) to 27 (very severe depression). Higher scores represent more severe depressive symptoms.

Posted

Least Squares Mean

95% Confidence Interval

units on a scale

up to 8 weeks

ID	Title	Description
OG000	Antidepressant + Placebo	Antidepressant + Placebo: Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + Placebo (oral, once daily) for 8 weeks.
OG001	Antidepressant + SPD489	Antidepressant + SPD489 (Lisdexamfetamine dimesylate): Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + SPD489 (optimized as a 20, 30, 50, or 70 mg dose, oral, once daily), for 8 weeks.

Secondary

Mean Change From Baseline in the Short Form-12 Health Survey V2 (SF-12V2)

Total score ranges from 0 (lowest level of health) - 100 (highest level of health) on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability (i.e. a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability). Higher scores are associated with better quality of life.

Posted

Least Squares Mean

95% Confidence Interval

units on a scale

up to 8 weeks

ID	Title	Description
OG000	Antidepressant + Placebo	Antidepressant + Placebo: Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + Placebo (oral, once daily) for 8 weeks.
OG001	Antidepressant + SPD489	Antidepressant + SPD489 (Lisdexamfetamine dimesylate): Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + SPD489 (optimized as a 20, 30, 50, or 70 mg dose, oral, once daily), for 8 weeks.

Secondary

Mean Change From Baseline in the Quality of Life Enjoyment Satisfaction Questionnaire Short Form (Q-LES-Q-SF)

The short form is a 16-item self-report questionnaire which evaluates general subject satisfaction with health, mood, relationships, functioning in daily life, and the treatment being taken. Overall level of satisfaction is evaluated on a 5-point scale from 1 (very poor) to 5 (very good). The total score ranges from 14-70 (last two items on the form are not included in the total score). A higher score indicates a better quality of life.

Posted

Least Squares Mean

95% Confidence Interval

units on a scale

up to 8 weeks

ID	Title	Description
OG000	Antidepressant + Placebo	Antidepressant + Placebo: Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + Placebo (oral, once daily) for 8 weeks.
OG001	Antidepressant + SPD489	Antidepressant + SPD489 (Lisdexamfetamine dimesylate): Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + SPD489 (optimized as a 20, 30, 50, or 70 mg dose, oral, once daily), for 8 weeks.

Secondary

Clinical Global Impressions - Global Improvement (CGI-I)

Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.

Posted

Number

percentage of participants

up to 8 weeks

ID	Title	Description
OG000	Antidepressant + Placebo	Antidepressant + Placebo: Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + Placebo (oral, once daily) for 8 weeks.
OG001	Antidepressant + SPD489	Antidepressant + SPD489 (Lisdexamfetamine dimesylate): Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + SPD489 (optimized as a 20, 30, 50, or 70 mg dose, oral, once daily), for 8 weeks.

Units

Secondary

Columbia Suicide Severity Rating Scale (C-SSRS)

C-SSRS is a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behavior occurred. The assessment is done by the nature of the responses, not by a numbered scale.

Posted

Number

percentage of participants

up to 8 weeks

ID	Title	Description
OG000	Antidepressant + Placebo	Antidepressant + Placebo: Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + Placebo (oral, once daily) for 8 weeks.
OG001	Antidepressant + SPD489	Antidepressant + SPD489 (Lisdexamfetamine dimesylate): Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + SPD489 (optimized as a 20, 30, 50, or 70 mg dose, oral, once daily), for 8 weeks.

Secondary

Amphetamine Cessation Symptom Assessment (ACSA)

ACSA scale has 16 symptom items rated on a scale from 0 (not at all) to 4 (extremely) with a possible total score range of 0 to 64. Higher scores indicate greater withdrawal symptom severity.

Posted

Mean

Standard Deviation

units on a scale

up to 8 weeks

ID	Title	Description
OG000	Antidepressant + Placebo	Antidepressant + Placebo: Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + Placebo (oral, once daily) for 8 weeks.
OG001	Antidepressant + SPD489	Antidepressant + SPD489 (Lisdexamfetamine dimesylate): Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) oral, once daily + SPD489 (optimized as a 20, 30, 50, or 70 mg dose, oral, once daily), for 8 weeks.

Units	Counts

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Antidepressant + Placebo	Oral, once daily antidepressant therapy (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release, or duloxetine hydrochloride) plus oral, once daily, double-blind placebo (matching SPD489).			5	201	54	201
EG001	Antidepressant + SPD489	Oral, once daily antidepressant therapy (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release or duloxetine hydrochloride), plus oral, once daily SPD489 (Lisdexamfetamine dimesylate optimized among 20, 30, 50 or 70 mg dose).			3	201	70	201

Serious Adverse Events

Term	Organ System	Statistical Information
Vertigo	Ear and labyrinth disorders	EG0001 events1 affected201 at risk EG0010 events0 affected201 at risk
Appendicitis	Infections and infestations	EG0000 events0 affected201 at risk EG0011 events1 affected201 at risk
Wound infection	Infections and infestations	EG0001 events1 affected201 at risk EG0010 events0 affected201 at risk
Accidental overdose	Injury, poisoning and procedural complications	EG0000 events0 affected201 at risk EG0011 events1 affected201 at risk
Laceration	Injury, poisoning and procedural complications	EG0001 events1 affected201 at risk EG0010 events0 affected201 at risk
Syncope	Nervous system disorders	EG0001 events1 affected201 at risk EG0011 events1 affected201 at risk
Major depression	Psychiatric disorders	EG0001 events1 affected201 at risk EG0010 events0 affected201 at risk
Suicide attempt	Psychiatric disorders	EG0001 events1 affected201 at risk EG0010 events0 affected201 at risk
Appendicectomy	Surgical and medical procedures	EG0001 events1 affected201 at risk EG0010 events0 affected201 at risk

Other Adverse Events

Term	Organ System	Statistical Information
Dry mouth	Gastrointestinal disorders	EG0006 events6 affected201 at risk EG00119 events19 affected201 at risk
Nausea	Gastrointestinal disorders	EG00011 events10 affected201 at risk EG00113 events13 affected201 at risk
Nasopharyngitis	Infections and infestations	EG0004 events4 affected201 at risk EG00112 events11 affected201 at risk
Decreased appetite	Metabolism and nutrition disorders	EG0008 events8 affected201 at risk EG00117 events15 affected201 at risk
Headache	Nervous system disorders	EG00028 events21 affected201 at risk EG00114 events13 affected201 at risk
Insomnia	Psychiatric disorders	EG00016 events15 affected201 at risk EG00120 events19 affected201 at risk

ID	Term
D003866	Depressive Disorder
D019964	Mood Disorders
D001523	Mental Disorders

ID	Term
D003913	Dextroamphetamine
D000661	Amphetamine
D000662	Amphetamines
D010627	Phenethylamines
D005021	Ethylamines
D000588	Amines
D009930	Organic Chemicals