Trial Outcomes & Findings for Efficacy and Safety Study of SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder (NCT NCT01436162)

NCT ID: NCT01436162

Last Updated: 2021-06-09

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1105 participants
• Primary outcome timeframe: 8 weeks
• Results posted on: 2021-06-09

Participant Flow

Participant milestones

Measure	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).	Antidepressant + Double-blind 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).	Antidepressant + Double-blind Placebo 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).
Single-blind Lead-in Phase STARTED	1105	0	0
Single-blind Lead-in Phase COMPLETED	823	0	0
Single-blind Lead-in Phase NOT COMPLETED	282	0	0
Randomized Phase STARTED	397	212	214
Randomized Phase COMPLETED	353	181	189
Randomized Phase NOT COMPLETED	44	31	25

Reasons for withdrawal

Measure	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).	Antidepressant + Double-blind 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).	Antidepressant + Double-blind Placebo 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).
Single-blind Lead-in Phase Adverse Event	26	0	0
Single-blind Lead-in Phase Protocol Violation	24	0	0
Single-blind Lead-in Phase Withdrawal by Subject	69	0	0
Single-blind Lead-in Phase Lost to Follow-up	43	0	0
Single-blind Lead-in Phase Met BP or Pulse Withdrawal Criteria	13	0	0
Single-blind Lead-in Phase Other	107	0	0
Randomized Phase Adverse Event	1	5	6
Randomized Phase Protocol Violation	4	4	2
Randomized Phase Withdrawal by Subject	16	9	8
Randomized Phase Lost to Follow-up	17	5	4
Randomized Phase Lack of Efficacy	0	1	1
Randomized Phase Met BP Or Pulse Withdrawal Criteria	4	2	0
Randomized Phase Other	2	5	4

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Antidepressant + Double-blind SPD489 n=211 Participants 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.	Antidepressant + Double-blind Placebo n=213 Participants 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 n=424 Participants Total of all reporting groups
Age, Continuous	42 Years STANDARD_DEVIATION 11.63 • n=5 Participants	42.6 Years STANDARD_DEVIATION 11.41 • n=7 Participants	42.3 Years STANDARD_DEVIATION 11.51 • n=5 Participants
Age, Customized 18-55 years	181 Participants n=5 Participants	184 Participants n=7 Participants	365 Participants n=5 Participants
Age, Customized 56-65 years	30 Participants n=5 Participants	29 Participants n=7 Participants	59 Participants n=5 Participants
Sex: Female, Male Female	141 Participants n=5 Participants	143 Participants n=7 Participants	284 Participants n=5 Participants
Sex: Female, Male Male	70 Participants n=5 Participants	70 Participants n=7 Participants	140 Participants n=5 Participants

PRIMARY outcome

Timeframe: 8 weeks

Population: 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).

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.

Outcome measures

Measure	Antidepressant + SPD489 n=209 Participants 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 n=213 Participants 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.
Mean Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at 8 Weeks	-7.3 units on a scale Interval -8.6 to -6.0	-6.8 units on a scale Interval -8.1 to -5.5

SECONDARY outcome

Timeframe: 8 weeks

Population: 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).

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.

Outcome measures

Measure	Antidepressant + SPD489 n=209 Participants 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 n=213 Participants 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.
Mean Change From Baseline in Sheehan Disability Scale (SDS) Total Score at 8 Weeks	-4.9 units on a scale Interval -5.8 to -4.0	-4.3 units on a scale Interval -5.2 to -3.4

SECONDARY outcome

Timeframe: Up to 8 weeks

Population: 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).

The percentage of subjects who achieved a 25% response (i.e. ≥25% reduction in MADRS total score from the Lead-in Baseline, Visit 2).

Outcome measures

Measure	Antidepressant + SPD489 n=209 Participants 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 n=213 Participants 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.
Percentage of Participants Achieving a 25% Response on the MADRS	68.9 percentage of participants	74.2 percentage of participants

SECONDARY outcome

Timeframe: Up to 8 weeks

Population: 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).

The percentage of subjects who achieved a 50% response (i.e. ≥50% reduction in MADRS total score from the Lead-in Baseline, Visit 2).

Outcome measures

Measure	Antidepressant + SPD489 n=209 Participants 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 n=213 Participants 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.
Percentage of Participants Achieving a 50% Response on the MADRS	41.6 percentage of participants	37.1 percentage of participants

SECONDARY outcome

Timeframe: Up to 8 weeks

Population: 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).

MADRS remission was defined as a MADRS total score of ≤10.

Outcome measures

Measure	Antidepressant + SPD489 n=209 Participants 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 n=213 Participants 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.
Percent of Participants Achieving Remission on the MADRS	23.0 percentage of participants	17.8 percentage of participants

SECONDARY outcome

Timeframe: Up to 8 weeks

Population: 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.

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.

Outcome measures

Measure	Antidepressant + SPD489 n=209 Participants 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 n=213 Participants 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.
Mean Change From Baseline Over Time in MADRS Total Score Week 9 (Visit 9)	-2.9 units on a scale Interval -3.9 to -2.0	-2.1 units on a scale Interval -3.0 to -1.1
Mean Change From Baseline Over Time in MADRS Total Score Week 10 (Visit 10)	-4.4 units on a scale Interval -5.5 to -3.3	-4.3 units on a scale Interval -5.4 to -3.2
Mean Change From Baseline Over Time in MADRS Total Score Week 11 (Visit 11)	-5.9 units on a scale Interval -7.1 to -4.7	-5.0 units on a scale Interval -6.2 to -3.8
Mean Change From Baseline Over Time in MADRS Total Score Week 12 (Visit 12)	-6.3 units on a scale Interval -7.6 to -5.1	-5.3 units on a scale Interval -6.5 to -4.1
Mean Change From Baseline Over Time in MADRS Total Score Week 14 (Visit 13)	-6.9 units on a scale Interval -8.2 to -5.5	-6.4 units on a scale Interval -7.7 to -5.1
Mean Change From Baseline Over Time in MADRS Total Score Week 16 (Visit 14)	-7.3 units on a scale Interval -8.6 to -6.0	-6.8 units on a scale Interval -8.1 to -5.5

SECONDARY outcome

Timeframe: up to 8 weeks

Population: 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).

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.

Outcome measures

Measure	Antidepressant + SPD489 n=194 Participants 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 n=198 Participants 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.
Mean Change From Baseline in Abbreviated Brief Assessment of Cognition Affective Disorders (ABAC-A) Composite T-Scores	3.0 t-score Interval 2.1 to 4.0	2.5 t-score Interval 1.5 to 3.5

SECONDARY outcome

Timeframe: Up to 8 weeks

Population: 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).

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.

Outcome measures

Measure	Antidepressant + SPD489 n=196 Participants 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 n=205 Participants 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.
Mean Change From Baseline in the Short Form-12 Health Survey V2 (SF-12V2) Physical	1.07 units on a scale Interval 0.04 to 2.1	0.90 units on a scale Interval -0.11 to 1.91
Mean Change From Baseline in the Short Form-12 Health Survey V2 (SF-12V2) Mental	6.63 units on a scale Interval 5.03 to 8.23	5.16 units on a scale Interval 3.6 to 6.73

SECONDARY outcome

Timeframe: Up to 8 weeks

Population: 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).

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.

Outcome measures

Measure	Antidepressant + SPD489 n=64 Participants 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 n=67 Participants 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.
Mean Change in Sexual Functioning Questionnaire - 14 Item Scale (CSFQ-14) Total Score Male	2.1 units on a scale Standard Deviation 6.22	1.0 units on a scale Standard Deviation 6.02

SECONDARY outcome

Timeframe: Up to 8 weeks

Population: 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).

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.

Outcome measures

Measure	Antidepressant + SPD489 n=125 Participants 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 n=133 Participants 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.
Mean Change in Sexual Functioning Questionnaire - 14 Item Scale (CSFQ-14) Total Score Female	3.0 units on a scale Standard Deviation 7.11	1.9 units on a scale Standard Deviation 5.82

SECONDARY outcome

Timeframe: Up to 8 weeks

Population: 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).

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.

Outcome measures

Measure	Antidepressant + SPD489 n=209 Participants 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 n=213 Participants 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.
Clinical Global Impressions - Global Improvement (CGI-I) Improved	56.9 percentage of participants	53.5 percentage of participants
Clinical Global Impressions - Global Improvement (CGI-I) Not Improved	43.1 percentage of participants	46.5 percentage of participants
Clinical Global Impressions - Global Improvement (CGI-I) Not Assessed	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Up to 8 weeks

Population: 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).

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.

Outcome measures

Measure	Antidepressant + SPD489 n=197 Participants 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 n=205 Participants 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.
Mean Change From Baseline in the Multidimensional Assessment of Fatigue (MAF) Global Fatigue Index (GFI)	-6.6 units on a scale Standard Error 0.74	-4.4 units on a scale Standard Error 0.73

SECONDARY outcome

Timeframe: Up to 8 weeks

Population: 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).

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.

Outcome measures

Measure	Antidepressant + SPD489 n=211 Participants 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 n=213 Participants 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.
Columbia Suicide Severity Rating Scale (C-SSRS) ≥1 positive suicidal ideation	9.0 percentage of participants	9.4 percentage of participants
Columbia Suicide Severity Rating Scale (C-SSRS) ≥1 suicidal attempt	0 percentage of participants	0.5 percentage of participants

SECONDARY outcome

Timeframe: 8 weeks

Population: 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).

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.

Outcome measures

Measure	Antidepressant + SPD489 n=194 Participants 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 n=199 Participants 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.
Amphetamine Cessation Symptom Assessment (ACSA) - Total Aggregate Score	17.0 Score Standard Deviation 10.80	17.2 Score Standard Deviation 10.56

Adverse Events

SPD489

Serious events: 1 serious events

Other events: 72 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Measure	SPD489 n=211 participants at risk 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	Placebo n=213 participants at risk 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
Psychiatric disorders Suicidal ideation	0.00% 0/211	0.47% 1/213 • Number of events 1
Vascular disorders Accelerated hypertension	0.47% 1/211 • Number of events 1	0.00% 0/213

Other adverse events

Measure	SPD489 n=211 participants at risk 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	Placebo n=213 participants at risk 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
Gastrointestinal disorders Dry mouth	11.8% 25/211 • Number of events 29	2.8% 6/213 • Number of events 6
Infections and infestations Nasopharyngitis	6.6% 14/211 • Number of events 14	8.9% 19/213 • Number of events 20
Metabolism and nutrition disorders Decreased appetite	6.2% 13/211 • Number of events 14	2.3% 5/213 • Number of events 5
Nervous system disorders Headache	11.8% 25/211 • Number of events 32	7.5% 16/213 • Number of events 22
Psychiatric disorders Insomnia	5.2% 11/211 • Number of events 14	3.3% 7/213 • Number of events 7
Skin and subcutaneous tissue disorders Hyperhidrosis	5.2% 11/211 • Number of events 16	0.47% 1/213 • Number of events 1

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER