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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3 Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, 26-week, Dose-optimization Study to Evaluate the Efficacy, Safety, and Tolerability of SPD489 Low Dose Range (40mg, 80mg, 100mg) and High Dose Range (120mg, 140mg, 160mg) as Adjunctive Treatment to Established Maintenance Doses of Antipsychotic Medications on Negative Symptoms in Clinically Stable Adults Who Have Persistent Predominant Negative Symptoms of Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: SPD489 low dose range (40mg, 80mg, and 100mg)
* Drug: SPD489 high dose range (120mg, 140mg and 160mg)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPD489 Low Dose Range<br> | Drug: SPD489 low dose range (40mg, 80mg, and 100mg)<br>* 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<br>* Other names: lisdexamfetamine dimesylate, LDX, Vyvanse;|
| Experimental: SPD489 High Dose Range<br> | Drug: SPD489 high dose range (120mg, 140mg and 160mg)<br>* 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<br>* Other names: lisdexamfetamine dimesylate, LDX, Vyvanse;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* One capsule a day for 26 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Negative Symptom Assessment (NSA-16) Total Score at 26 Weeks |  | Baseline and 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Personal and Social Performance (PSP) Scale Score at 26 Weeks |  | Baseline and 26 weeks | 
| Change From Baseline in Simpson Angus Scale (SAS) Total Score at 26 Weeks |  | Baseline and 26 weeks | 
| Change From Baseline in Barnes Akathisia Scale (BAS) Total Score at 26 Weeks |  | Baseline and 26 weeks | 
| Change From Baseline in the Abnormal Involuntary Movement Scale (AIMS) at 26 Weeks |  | Baseline and 26 weeks | 
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Scores at 26 Weeks |  | Baseline and 26 weeks | 
| Change From Baseline in Cognitive Test Battery (CogState Battery) Score at 26 Weeks |  | Baseline and 26 weeks | 
| Change From Baseline in Social Functioning Scale (SFS) at 26 Weeks |  | Baseline and 26 weeks | 
| Clinical Global Impression-Schizophrenia Severity of Illness (CGI-SCH-S) Scale |  | Baseline and week 26 | 
| Clinical Global Impression-Schizophrenia Degree of Change (CGI-SCH-C) Scale |  | Up to 26 weeks | 
| Change From Baseline in Amphetamine Cessation Symptom Assessment (ACSA) Total Score at 26 Weeks |  | Baseline and 26 weeks | 
| Change From Baseline in Clinical Evaluation of Harmful Behavior (CEHB) Scale at 26 Weeks |  | Baseline and 26 weeks | 
| Columbia-Suicide Severity Rating Scale (C-SSRS) |  | Up to 26 weeks | 
| Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) at 26 Weeks |  | Baseline and 26 weeks |