SPD489 Low Dose and High Dose Ranges When Added to Stable Doses of Antipsychotic Medications in Clinically Stable Adults With Negative Symptoms of Schizophrenia

• Change from Baseline in the Personal and Social Performance (PSP) Scale Score at 26 Weeks [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: No ]
• Change From Baseline in Simpson Angus Scale (SAS) Total Score at 26 Weeks [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: Yes ]
• Change From Baseline in Barnes Akathisia Scale (BAS) Total Score at 26 Weeks [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: Yes ]
• Change from Baseline in the Abnormal Involuntary Movement Scale (AIMS) at 26 Weeks [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: Yes ]
• Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Scores at 26 Weeks [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: No ]
• Change From Baseline in Cognitive Test Battery (CogState Battery) Score at 26 Weeks [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: No ]
• Change from Baseline in Social Functioning Scale (SFS) at 26 Weeks [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: No ]
• Clinical Global Impression-Schizophrenia Severity of Illness (CGI-SCH-S) Scale [ Time Frame: Baseline and week 26 ] [ Designated as safety issue: No ]
• Clinical Global Impression-Schizophrenia Degree of Change (CGI-SCH-C) Scale [ Time Frame: Up to 26 weeks ] [ Designated as safety issue: No ]
• Change From Baseline in Amphetamine Cessation Symptom Assessment (ACSA) Total Score at 26 Weeks [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: Yes ]
• Change from Baseline in Clinical Evaluation of Harmful Behavior (CEHB) Scale at 26 Weeks [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: Yes ]
• Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Up to 26 weeks ] [ Designated as safety issue: Yes ]
• Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) at 26 Weeks [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: Yes ]

The primary purpose of this study is to determine whether SPD489 low dose range (40, 80, or 100mg) and high dose range (120, 140, or 160mg) are effective in the treatment of Negative Symptoms.

• Drug: SPD489 low dose range (40mg, 80mg, and 100mg)

  Capsule, dose titration,

  • 40 mg capsule once-daily for 1 week; then
  • 80 mg capsule once-daily for 4 weeks; then,
  • 100 mg capsule once-daily (if unable to tolerate 100 mg dose between weeks 5 to 6, then dose to be decreased to 80 mg once-daily for the remaining 21 weeks;
  • if able to tolerate 100 mg dose then will continue on 100 mg capsule once-daily for 21 weeks
  Other Name: lisdexamfetamine dimesylate, LDX, Vyvanse
• Drug: SPD489 high dose range (120mg, 140mg and 160mg)

  Capsule, dose titration,

  • 40 mg capsule once-daily for 1 week; then
  • 80 mg capsule once daily for 1 week; then
  • 120 mg capsule once-daily for 1 week, then,
  • 140 mg capsule once-daily for 2 weeks, then
  • 160 mg once capsule once-daily (if unable to tolerate 160 mg dose between weeks 5 to 6, then dose to be decreased to 140 mg once-daily for the remaining 21 weeks;
  • if able to tolerate 160 mg dose then will continue on 160 mg capsule once-daily for 21 weeks
  Other Name: lisdexamfetamine dimesylate, LDX, Vyvanse
• Drug: Placebo
  One capsule a day for 26 weeks

• Experimental: SPD489 Low Dose Range
  Intervention: Drug: SPD489 low dose range (40mg, 80mg, and 100mg)
• Experimental: SPD489 High Dose Range
  Intervention: Drug: SPD489 high dose range (120mg, 140mg and 160mg)
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• - 18 to 65 years of age
• Has a reliable informant (eg, family member, social worker, caseworker, or nurse that spends >4 hours/week with the subject)
• Fixed home/place of residence and can be reached by telephone
• On a stable dose of antipsychotic medications
• Able to swallow capsules

Exclusion Criteria:

• Taking lithium, carbamazepine, lamotrigine, gabapentin, cholinesterase inhibitors, modafinil, or other stimulants such as methylphenidate and other amphetamine products
• Treated with clozapine in past 30 days
• Lifetime history of stimulant, cocaine, or amphetamine abuse or dependence
• History of seizures (other than infantile febrile seizures), any tic disorder, or 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
• Uncontrolled hypertension
• History of thyroid disorder that has not been stabilized on thyroid medication
• Glaucoma
• Pregnant or nursing
• Subject has received an investigational product or participated in a clinical study within 30 days