A Multiple Dose Study of Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ABT-288 in Stable Subjects With Schizophrenia

Study Overview
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Brief Summary
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Evaluate the safety, tolerability and pharmacokinetics of ABT-288 in order to determine the maximum tolerated dose of ABT-288 in stable schizophrenic volunteers receiving treatment with an atypical antipsychotic.

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: ABT-288
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has signed informed consent; Current DSM-IV-TR diagnosis of schizophrenia; Clinically stable on the same single second-generation antipsychotic for the past 8 weeks; Meets study-specific PANSS criteria; Willing and able to cooperate with cognitive testing Females are not pregnant, not breast-feeding; Females are post-menopausal or surgically sterile or practicing birth control; Males are surgically sterile or agree to be sexually inactive or use barrier method of birth control Exclusion Criteria: Subject has a substance dependence disorder that has not been in sustained remission for at least 1 year; Diagnosis of schizoaffective disorder; Bipolar disorder, manic episode, dementia, OCD, or drug-induced psychosis or current major depressive disorder; Diagnoses with mental retardation; acute psychosis hospitalization within past 6 months; Current clozapine treatment; suicidal ideation or behavior; BMI of 39 or greater; current homicidal or violent ideation; Medical or CNS condition other than schizophrenia that could affect cognitive performance or testing; relevant drug sensitivity or allergy; positive urine screen for alcohol or drugs of abuse; Positive hepatitis or HIV test result; Recent clinically significant illness/infection or surgery; Recent blood product transfusion, donation or loss of 5 mL/kg of blood; Visual, hearing or communication disability

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>ABT-288 vs placebo capsules administered orally once daily for 14 days | Drug: ABT-288<br>* See Arm Description for details.<br>Drug: Placebo<br>* See Arm Description for details.<br>|
| Experimental: 2<br>ABT-288 vs placebo capsules administered orally once daily for 14 days | Drug: ABT-288<br>* See Arm Description for details.<br>Drug: Placebo<br>* See Arm Description for details.<br>|
| Experimental: 3<br>ABT-288 vs placebo capsules administered orally once daily for 14 days | Drug: ABT-288<br>* See Arm Description for details.<br>Drug: Placebo<br>* See Arm Description for details.<br>|
| Experimental: 4<br>ABT288 vs placebo administered orally once daily for 14 days | Drug: ABT-288<br>* See Arm Description for details.<br>Drug: Placebo<br>* See Arm Description for details.<br>|
| Experimental: 5<br>ABT-288 vs placebo administered orally once daily for 14 days | Drug: ABT-288<br>* See Arm Description for details.<br>Drug: Placebo<br>* See Arm Description for details.<br>|
| Experimental: 6<br>ABT-288 vs placebo administered orally once daily for 14 days | Drug: ABT-288<br>* See Arm Description for details.<br>Drug: Placebo<br>* See Arm Description for details.<br>|
| Experimental: 7<br>ABT-288 vs placebo administered orally once daily for 14 days | Drug: ABT-288<br>* See Arm Description for details.<br>Drug: Placebo<br>* See Arm Description for details.<br>|
| Experimental: 8<br>ABT-288 vs placebo administered orally once daily for 14 days | Drug: ABT-288<br>* See Arm Description for details.<br>Drug: Placebo<br>* See Arm Description for details.<br>|
| Experimental: 9<br>ABT-288 vs placebo administered orally once daily for 14 days | Drug: ABT-288<br>* See Arm Description for details.<br>Drug: Placebo<br>* See Arm Description for details.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical Exams, Brief Neurological Exams, Vitals, Orthostatic Vitals, ECG, Laboratory tests, |  | Days -1 to 21 | 
| Pharmacokinetics; optional CSF for arms 7, 8 & 9 |  | Days -1 to 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extrapyramidal Symptom Rating Scale |  | Day -1, Day 14 | 
| Columbia Suicide Severity Rating Scale |  | Screening, Day 15 | 
| Pharmacodynamics: CANTAB & PANSS |  | Screening, Day -1, Day 14 | 
| Pharmacodynamics: Pittsburgh Sleep Quality Index-Modified |  | Day -1, Day 15 |