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Trial record 5 of 1020 for:    "Depressive Disorder" [DISEASE] AND Rating AND Major Depressive Disorder AND Antidepressive Agents

Efficacy and Safety Study of SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01436162
Recruitment Status : Completed
First Posted : September 19, 2011
Results First Posted : November 7, 2014
Last Update Posted : December 19, 2018
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: Antidepressant + SPD489 (Lisdexamfetamine dimesylate )
Drug: Antidepressant + Placebo
Enrollment 1105
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Antidepressant + Single-blind Placebo Antidepressant + Double-blind SPD489 Antidepressant + Double-blind Placebo
Hide Arm/Group Description 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). Subjects received assigned 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 a 20, 30, 50, or 70 mg dose). Subjects received assigned 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).
Period Title: Single-blind Lead-in Phase
Started 1105 [1] 0 0
Completed 823 0 0
Not Completed 282 0 0
Reason Not Completed
Adverse Event             26             0             0
Protocol Violation             24             0             0
Withdrawal by Subject             69             0             0
Lost to Follow-up             43             0             0
Met BP or Pulse Withdrawal Criteria             13             0             0
Not Specified             107             0             0
[1]
Ten subjects were enrolled but not dosed.
Period Title: Randomized Phase
Started 397 [1] 212 [2] 214 [2]
Completed 353 181 189
Not Completed 44 31 25
Reason Not Completed
Adverse Event             1             5             6
Protocol Violation             4             4             2
Withdrawal by Subject             16             9             8
Lost to Follow-up             17             5             4
Lack of Efficacy             0             1             1
Met BP Or Pulse Withdrawal Criteria             4             2             0
Not Specified             2             5             4
[1]
These subjects were not included in the Safety Analysis Set or Full Analysis Set.
[2]
One subject was randomized to this arm but did not receive at least 1 dose of double-blind treatment
Arm/Group Title Antidepressant + Double-blind SPD489 Antidepressant + Double-blind Placebo Total
Hide Arm/Group Description Subjects received assigned 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 a 20, 30, 50, or 70 mg dose) for 8 weeks. Subjects received assigned 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. Total of all reporting groups
Overall Number of Baseline Participants 211 213 424
Hide Baseline Analysis Population Description
Safety Analysis Set: All subjects who took at least 1 dose of randomized investigational product and who had at least 1 safety assessment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 211 participants 213 participants 424 participants
42  (11.63) 42.6  (11.41) 42.3  (11.51)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 211 participants 213 participants 424 participants
18-55 years 181 184 365
56-65 years 30 29 59
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 211 participants 213 participants 424 participants
Female
141
  66.8%
143
  67.1%
284
  67.0%
Male
70
  33.2%
70
  32.9%
140
  33.0%
1.Primary Outcome
Title Mean Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at 8 Weeks
Hide Description 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.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Antidepressant + SPD489 Antidepressant + Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 209 213
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-7.3
(-8.6 to -6.0)
-6.8
(-8.1 to -5.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Antidepressant + SPD489, Antidepressant + Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.583
Comments [Not Specified]
Method Mixed-effects Model for Repeat Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-2.3 to 1.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.92
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Mean Change From Baseline in Sheehan Disability Scale (SDS) Total Score at 8 Weeks
Hide Description 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.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Antidepressant + SPD489 Antidepressant + Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 209 213
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-4.9
(-5.8 to -4.0)
-4.3
(-5.2 to -3.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Antidepressant + SPD489, Antidepressant + Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.354
Comments [Not Specified]
Method Mixed-effects Model for Repeat Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.9 to 0.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.65
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants Achieving a 25% Response on the MADRS
Hide Description The percentage of subjects who achieved a 25% response (i.e. ≥25% reduction in MADRS total score from the Lead-in Baseline, Visit 2).
Time Frame Up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Antidepressant + SPD489 Antidepressant + Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 209 213
Measure Type: Number
Unit of Measure: percentage of participants
68.9 74.2
4.Secondary Outcome
Title Percentage of Participants Achieving a 50% Response on the MADRS
Hide Description The percentage of subjects who achieved a 50% response (i.e. ≥50% reduction in MADRS total score from the Lead-in Baseline, Visit 2).
Time Frame Up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Antidepressant + SPD489 Antidepressant + Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 209 213
Measure Type: Number
Unit of Measure: percentage of participants
41.6 37.1
5.Secondary Outcome
Title Percent of Participants Achieving Remission on the MADRS
Hide Description MADRS remission was defined as a MADRS total score of ≤10.
Time Frame Up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Antidepressant + SPD489 Antidepressant + Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 209 213
Measure Type: Number
Unit of Measure: percentage of participants
23.0 17.8
6.Secondary Outcome
Title Mean Change From Baseline Over Time in MADRS Total Score
Hide Description 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.
Time Frame Up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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 MADRS total score after the Augmentation Baseline Visit (Visit 8). Sample size (n) of MADRS total score at each visit differed from sample size (N) of the FAS.
Arm/Group Title Antidepressant + SPD489 Antidepressant + Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 209 213
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Week 9 (Visit 9)
-2.9
(-3.9 to -2.0)
-2.1
(-3.0 to -1.1)
Week 10 (Visit 10)
-4.4
(-5.5 to -3.3)
-4.3
(-5.4 to -3.2)
Week 11 (Visit 11)
-5.9
(-7.1 to -4.7)
-5.0
(-6.2 to -3.8)
Week 12 (Visit 12)
-6.3
(-7.6 to -5.1)
-5.3
(-6.5 to -4.1)
Week 14 (Visit 13)
-6.9
(-8.2 to -5.5)
-6.4
(-7.7 to -5.1)
Week 16 (Visit 14)
-7.3
(-8.6 to -6.0)
-6.8
(-8.1 to -5.5)
7.Secondary Outcome
Title Mean Change From Baseline in Abbreviated Brief Assessment of Cognition Affective Disorders (ABAC-A) Composite T-Scores
Hide Description The ABAC-A is a rater-administered series of activities designed to be sensitive to the critical cognitive deficits in affective disorders and schizophrenia. There are 6 subtests of the ABAC-A: List Learning (verbal memory); Digit Sequencing Task (working memory); Token Motor Task (motor speed); Verbal Fluency; Symbol Coding (attention and processing speed); and Tower of London Test (executive functions). The ABAC-A Composite T-score change from Augmentation Baseline Visit (Visit 8; Week 8) at Visit 14/Early Termination (ET) (Week 16/ET) was analyzed.
Time Frame up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Antidepressant + SPD489 Antidepressant + Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 194 198
Least Squares Mean (95% Confidence Interval)
Unit of Measure: t-score
3.0
(2.1 to 4.0)
2.5
(1.5 to 3.5)
8.Secondary Outcome
Title Mean Change From Baseline in the Short Form-12 Health Survey V2 (SF-12V2)
Hide Description 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.
Time Frame Up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Antidepressant + SPD489 Antidepressant + Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 196 205
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Physical
1.07
(0.04 to 2.10)
0.90
(-0.11 to 1.91)
Mental
6.63
(5.03 to 8.23)
5.16
(3.60 to 6.73)
9.Secondary Outcome
Title Mean Change in Sexual Functioning Questionnaire - 14 Item Scale (CSFQ-14) Total Score Male
Hide Description The CSFQ-14 is a short-form interview/questionnaire that measures illness- and medication-related changes in sexual functioning. A 5-point Likert scale is used ranging from 1 (never) to 5 (always). The CSFQ-14 total score can range from 14 to 70, with lower scores being associated with worsened sexual functioning.
Time Frame Up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: Male 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).
Arm/Group Title Antidepressant + SPD489 Antidepressant + Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 64 67
Mean (Standard Deviation)
Unit of Measure: units on a scale
2.1  (6.22) 1.0  (6.02)
10.Secondary Outcome
Title Mean Change in Sexual Functioning Questionnaire - 14 Item Scale (CSFQ-14) Total Score Female
Hide Description The CSFQ-14 is a short-form interview/questionnaire that measures illness- and medication-related changes in sexual functioning. A 5-point Likert scale is used ranging from 1 (never) to 5 (always). The CSFQ-14 total score can range from 14 to 70, with lower scores being associated with worsened sexual functioning.
Time Frame Up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: Female 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).
Arm/Group Title Antidepressant + SPD489 Antidepressant + Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 125 133
Mean (Standard Deviation)
Unit of Measure: units on a scale
3.0  (7.11) 1.9  (5.82)
11.Secondary Outcome
Title Clinical Global Impressions - Global Improvement (CGI-I)
Hide Description 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.
Time Frame Up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Antidepressant + SPD489 Antidepressant + Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 209 213
Measure Type: Number
Unit of Measure: percentage of participants
Improved 56.9 53.5
Not Improved 43.1 46.5
Not Assessed 0 0
12.Secondary Outcome
Title Mean Change From Baseline in the Multidimensional Assessment of Fatigue (MAF) Global Fatigue Index (GFI)
Hide Description MAF contains 16 items scored on a scale from 1 (not at all) to 10 (a great deal). Answers are converted to a Global Fatigue Index with total scores ranging from 1 (no fatigue) to 50 (severe fatigue). Lower scores indicate less fatigue.
Time Frame Up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Antidepressant + SPD489 Antidepressant + Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 197 205
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-6.6  (0.74) -4.4  (0.73)
13.Secondary Outcome
Title Columbia Suicide Severity Rating Scale (C-SSRS)
Hide Description C-SSRS is a semi-structured interview that captures the occurence, 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 behaviour occurred. The assessment is done by the nature of the responses, not by a numbered scale.
Time Frame Up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: All subjects who took at least 1 dose of randomized investigational product and who had at least 1 safety assessment (e.g., coming back for any visit, reporting of an adverse event [AE], or reporting the absence of AEs) after the Augmentation Baseline Visit (Visit 8).
Arm/Group Title Antidepressant + SPD489 Antidepressant + Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 211 213
Measure Type: Number
Unit of Measure: percentage of participants
≥1 positive suicidal ideation 9.0 9.4
≥1 suicidal attempt 0 0.5
14.Secondary Outcome
Title Amphetamine Cessation Symptom Assessment (ACSA) - Total Aggregate Score
Hide Description 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.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: All subjects who took at least 1 dose of randomized investigational product and who had at least 1 safety assessment (e.g., coming back for any visit, reporting of an AE, or reporting the absence of AEs) after the Augmentation Baseline Visit (Visit 8).
Arm/Group Title Antidepressant + SPD489 Antidepressant + Placebo
Hide Arm/Group Description:
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.
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
Overall Number of Participants Analyzed 194 199
Mean (Standard Deviation)
Unit of Measure: Score
17.0  (10.80) 17.2  (10.56)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title SPD489 Placebo
Hide Arm/Group Description Antidepressant + SPD489 (Lisdexamfetamine dimesylate ): 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 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
All-Cause Mortality
SPD489 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
SPD489 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/211 (0.47%)      1/213 (0.47%)    
Psychiatric disorders     
Suicidal ideation  0/211 (0.00%)  0 1/213 (0.47%)  1
Vascular disorders     
Accelerated hypertension  1/211 (0.47%)  1 0/213 (0.00%)  0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
SPD489 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   72/211 (34.12%)      46/213 (21.60%)    
Gastrointestinal disorders     
Dry mouth  25/211 (11.85%)  29 6/213 (2.82%)  6
Infections and infestations     
Nasopharyngitis  14/211 (6.64%)  14 19/213 (8.92%)  20
Metabolism and nutrition disorders     
Decreased appetite  13/211 (6.16%)  14 5/213 (2.35%)  5
Nervous system disorders     
Headache  25/211 (11.85%)  32 16/213 (7.51%)  22
Psychiatric disorders     
Insomnia  11/211 (5.21%)  14 7/213 (3.29%)  7
Skin and subcutaneous tissue disorders     
Hyperhidrosis  11/211 (5.21%)  16 1/213 (0.47%)  1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Physician
Organization: Shire Development LLC
Phone: +1 866 842 5335
Layout table for additonal information
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01436162     History of Changes
Other Study ID Numbers: SPD489-323
2011-003006-25 ( EudraCT Number )
First Submitted: September 15, 2011
First Posted: September 19, 2011
Results First Submitted: October 31, 2014
Results First Posted: November 7, 2014
Last Update Posted: December 19, 2018