Assess the Safety and Pharmacokinetics of Ascending, Multiple Oral Doses of SPD489 in Adults With Schizophrenia

Schizophrenia Clinical Trial

Official title:

A Phase 1, Randomized, Double-blind, Placebo Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ascending, Multiple Oral Doses of SPD489 (Lisdexamfetamine Dimesylate) in Clinically Stable Adults With Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01457339
• Other study ID #: SPD489-119
• Status: Completed
• Phase: Phase 1
• Start date: October 21, 2011
• Est. completion date: January 20, 2012

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multiple ascending dose study; the purpose of this study is to examine the safety, tolerability and pharmacokinetics (levels of drug in the blood) of SPD489 in Schizophrenic Patients who are currently maintained on a stable dose of an antipsychotic medication.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: January 20, 2012
• Est. primary completion date: January 20, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Subjects must be diagnosed with schizophrenia, on a stable dose of an antipsychotic and not have any cardiac risk factors

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• SPD489 (Lisdexamfetamine dimesylate)
SPD489 administered orally in ascending doses (50mg, 70mg, 100mg, 150mg, 200mg, 250mg). Each of these doses will be administered once daily for 5 days. Total number of days dosed is 30 days.
• Placebo
Placebo Capsule(s) for oral use taken once daily for 30 days

Locations

Country	Name	City	State
United States	California Clinical Trials	Glendale	California
United States	Collaborative Neuroscience Network, Inc	Long Beach	California

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Systolic Blood Pressure at Day 5: 50 mg	Blood pressure and pulse measurements were taken using an automated blood pressure monitoring device (ideally using the same device, the same arm and in the same position throughout the study). Measurements of vital signs were performed in triplicate (3 measurements) after the subject had been in a sitting position for at least 5 minutes. Each of the 3 triplicate readings were performed in succession, at least 1-2 minutes apart, with the cuff fully deflated between measurements. It was expected that the triplicate measurements be obtained within a 5-6 minute period.	Baseline and day 5
Primary	Change From Baseline in Systolic Blood Pressure at Day 5: 70 mg	Blood pressure and pulse measurements were taken using an automated blood pressure monitoring device (ideally using the same device, the same arm and in the same position throughout the study). Measurements of vital signs were performed in triplicate (3 measurements) after the subject had been in a sitting position for at least 5 minutes. Each of the 3 triplicate readings were performed in succession, at least 1-2 minutes apart, with the cuff fully deflated between measurements. It was expected that the triplicate measurements be obtained within a 5-6 minute period.	Baseline and day 5
Primary	Change From Baseline in Systolic Blood Pressure at Day 5: 100 mg	Blood pressure and pulse measurements were taken using an automated blood pressure monitoring device (ideally using the same device, the same arm and in the same position throughout the study). Measurements of vital signs were performed in triplicate (3 measurements) after the subject had been in a sitting position for at least 5 minutes. Each of the 3 triplicate readings were performed in succession, at least 1-2 minutes apart, with the cuff fully deflated between measurements. It was expected that the triplicate measurements be obtained within a 5-6 minute period.	Baseline and day 5
Primary	Change From Baseline in Systolic Blood Pressure at Day 5: 150 mg	Blood pressure and pulse measurements were taken using an automated blood pressure monitoring device (ideally using the same device, the same arm and in the same position throughout the study). Measurements of vital signs were performed in triplicate (3 measurements) after the subject had been in a sitting position for at least 5 minutes. Each of the 3 triplicate readings were performed in succession, at least 1-2 minutes apart, with the cuff fully deflated between measurements. It was expected that the triplicate measurements be obtained within a 5-6 minute period.	Baseline and day 5
Primary	Change From Baseline in Systolic Blood Pressure at Day 5: 200 mg	Blood pressure and pulse measurements were taken using an automated blood pressure monitoring device (ideally using the same device, the same arm and in the same position throughout the study). Measurements of vital signs were performed in triplicate (3 measurements) after the subject had been in a sitting position for at least 5 minutes. Each of the 3 triplicate readings were performed in succession, at least 1-2 minutes apart, with the cuff fully deflated between measurements. It was expected that the triplicate measurements be obtained within a 5-6 minute period.	Baseline and day 5
Primary	Change From Baseline in Systolic Blood Pressure at Day 5: 250 mg	Blood pressure and pulse measurements were taken using an automated blood pressure monitoring device (ideally using the same device, the same arm and in the same position throughout the study). Measurements of vital signs were performed in triplicate (3 measurements) after the subject had been in a sitting position for at least 5 minutes. Each of the 3 triplicate readings were performed in succession, at least 1-2 minutes apart, with the cuff fully deflated between measurements. It was expected that the triplicate measurements be obtained within a 5-6 minute period.	Baseline and day 5
Primary	Change From Baseline in Diastolic Blood Pressure at Day 5: 50 mg	Blood pressure and pulse measurements were taken using an automated blood pressure monitoring device (ideally using the same device, the same arm and in the same position throughout the study). Measurements of vital signs were performed in triplicate (3 measurements) after the subject had been in a sitting position for at least 5 minutes. Each of the 3 triplicate readings were performed in succession, at least 1-2 minutes apart, with the cuff fully deflated between measurements. It was expected that the triplicate measurements be obtained within a 5-6 minute period.	Baseline and day 5
Primary	Change From Baseline in Diastolic Blood Pressure at Day 5: 70 mg	Blood pressure and pulse measurements were taken using an automated blood pressure monitoring device (ideally using the same device, the same arm and in the same position throughout the study). Measurements of vital signs were performed in triplicate (3 measurements) after the subject had been in a sitting position for at least 5 minutes. Each of the 3 triplicate readings were performed in succession, at least 1-2 minutes apart, with the cuff fully deflated between measurements. It was expected that the triplicate measurements be obtained within a 5-6 minute period.	Baseline and day 5
Primary	Change From Baseline in Diastolic Blood Pressure at Day 5: 100 mg	Blood pressure and pulse measurements were taken using an automated blood pressure monitoring device (ideally using the same device, the same arm and in the same position throughout the study). Measurements of vital signs were performed in triplicate (3 measurements) after the subject had been in a sitting position for at least 5 minutes. Each of the 3 triplicate readings were performed in succession, at least 1-2 minutes apart, with the cuff fully deflated between measurements. It was expected that the triplicate measurements be obtained within a 5-6 minute period.	Baseline and day 5
Primary	Change From Baseline in Diastolic Blood Pressure at Day 5: 150 mg	Blood pressure and pulse measurements were taken using an automated blood pressure monitoring device (ideally using the same device, the same arm and in the same position throughout the study). Measurements of vital signs were performed in triplicate (3 measurements) after the subject had been in a sitting position for at least 5 minutes. Each of the 3 triplicate readings were performed in succession, at least 1-2 minutes apart, with the cuff fully deflated between measurements. It was expected that the triplicate measurements be obtained within a 5-6 minute period.	Baseline and day 5
Primary	Change From Baseline in Diastolic Blood Pressure at Day 5: 200 mg	Blood pressure and pulse measurements were taken using an automated blood pressure monitoring device (ideally using the same device, the same arm and in the same position throughout the study). Measurements of vital signs were performed in triplicate (3 measurements) after the subject had been in a sitting position for at least 5 minutes. Each of the 3 triplicate readings were performed in succession, at least 1-2 minutes apart, with the cuff fully deflated between measurements. It was expected that the triplicate measurements be obtained within a 5-6 minute period.	Baseline and day 5
Primary	Change From Baseline in Diastolic Blood Pressure at Day 5: 250 mg	Blood pressure and pulse measurements were taken using an automated blood pressure monitoring device (ideally using the same device, the same arm and in the same position throughout the study). Measurements of vital signs were performed in triplicate (3 measurements) after the subject had been in a sitting position for at least 5 minutes. Each of the 3 triplicate readings were performed in succession, at least 1-2 minutes apart, with the cuff fully deflated between measurements. It was expected that the triplicate measurements be obtained within a 5-6 minute period.	Baseline and day 5
Primary	Change From Baseline in Pulse Rate at Day 5: 50 mg	Blood pressure and pulse measurements were taken using an automated blood pressure monitoring device (ideally using the same device, the same arm and in the same position throughout the study). Measurements of vital signs were performed in triplicate (3 measurements) after the subject had been in a sitting position for at least 5 minutes. Each of the 3 triplicate readings were performed in succession, at least 1-2 minutes apart, with the cuff fully deflated between measurements. It was expected that the triplicate measurements be obtained within a 5-6 minute period.	Baseline and day 5
Primary	Change From Baseline in Pulse Rate at Day 5: 70 mg	Blood pressure and pulse measurements were taken using an automated blood pressure monitoring device (ideally using the same device, the same arm and in the same position throughout the study). Measurements of vital signs were performed in triplicate (3 measurements) after the subject had been in a sitting position for at least 5 minutes. Each of the 3 triplicate readings were performed in succession, at least 1-2 minutes apart, with the cuff fully deflated between measurements. It was expected that the triplicate measurements be obtained within a 5-6 minute period.	Baseline and day 5
Primary	Change From Baseline in Pulse Rate at Day 5: 100 mg	Blood pressure and pulse measurements were taken using an automated blood pressure monitoring device (ideally using the same device, the same arm and in the same position throughout the study). Measurements of vital signs were performed in triplicate (3 measurements) after the subject had been in a sitting position for at least 5 minutes. Each of the 3 triplicate readings were performed in succession, at least 1-2 minutes apart, with the cuff fully deflated between measurements. It was expected that the triplicate measurements be obtained within a 5-6 minute period.	Baseline and day 5
Primary	Change From Baseline in Pulse Rate at Day 5: 150 mg	Blood pressure and pulse measurements were taken using an automated blood pressure monitoring device (ideally using the same device, the same arm and in the same position throughout the study). Measurements of vital signs were performed in triplicate (3 measurements) after the subject had been in a sitting position for at least 5 minutes. Each of the 3 triplicate readings were performed in succession, at least 1-2 minutes apart, with the cuff fully deflated between measurements. It was expected that the triplicate measurements be obtained within a 5-6 minute period.	Baseline and day 5
Primary	Change From Baseline in Pulse Rate at Day 5: 200 mg	Blood pressure and pulse measurements were taken using an automated blood pressure monitoring device (ideally using the same device, the same arm and in the same position throughout the study). Measurements of vital signs were performed in triplicate (3 measurements) after the subject had been in a sitting position for at least 5 minutes. Each of the 3 triplicate readings were performed in succession, at least 1-2 minutes apart, with the cuff fully deflated between measurements. It was expected that the triplicate measurements be obtained within a 5-6 minute period.	Baseline and day 5
Primary	Change From Baseline in Pulse Rate at Day 5: 250 mg	Blood pressure and pulse measurements were taken using an automated blood pressure monitoring device (ideally using the same device, the same arm and in the same position throughout the study). Measurements of vital signs were performed in triplicate (3 measurements) after the subject had been in a sitting position for at least 5 minutes. Each of the 3 triplicate readings were performed in succession, at least 1-2 minutes apart, with the cuff fully deflated between measurements. It was expected that the triplicate measurements be obtained within a 5-6 minute period.	Baseline and day 5
Secondary	Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Lisdexamfetamine Dimesylate on Day 5: 50 mg	AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.	Day 5 (12-hour sampling period post-dose)
Secondary	Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Lisdexamfetamine Dimesylate on Day 5: 70 mg	AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.	Day 5 (12-hour sampling period post-dose)
Secondary	Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Lisdexamfetamine Dimesylate on Day 5: 100 mg	AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.	Day 5 (12-hour sampling period post-dose)
Secondary	Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Lisdexamfetamine Dimesylate on Day 5: 150 mg	AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.	Day 5 (12-hour sampling period post-dose)
Secondary	Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Lisdexamfetamine Dimesylate on Day 5: 200 mg	AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.	Day 5 (12-hour sampling period post-dose)
Secondary	Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Lisdexamfetamine Dimesylate on Day 5: 250 mg	AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.	Day 5 (12-hour sampling period post-dose)
Secondary	Maximum Plasma Concentration (Cmax) of Lisdexamfetamine Dimesylate on Day 5: 50 mg	Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated.	Day 5 (12-hour sampling period post-dose)
Secondary	Maximum Plasma Concentration (Cmax) of Lisdexamfetamine Dimesylate on Day 5: 70 mg	Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated.	Day 5 (12-hour sampling period post-dose)
Secondary	Maximum Plasma Concentration (Cmax) of Lisdexamfetamine Dimesylate on Day 5: 100 mg	Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated.	Day 5 (12-hour sampling period post-dose)
Secondary	Maximum Plasma Concentration (Cmax) of Lisdexamfetamine Dimesylate on Day 5: 150 mg	Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated.	Day 5 (12-hour sampling period post-dose)
Secondary	Maximum Plasma Concentration (Cmax) of Lisdexamfetamine Dimesylate on Day 5: 200 mg	Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated.	Day 5 (12-hour sampling period post-dose)
Secondary	Maximum Plasma Concentration (Cmax) of Lisdexamfetamine Dimesylate on Day 5: 250 mg	Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated.	Day 5 (12-hour sampling period post-dose)
Secondary	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 5: 50 mg	The PANSS is a validated measure that evaluates the presence, absence, and severity of 30 symptoms of schizophrenia including both positive and negative symptoms and general psychopathology. Each of the 30-items are rated on a scale of 1 (absent) to 7 (extreme) with a total scoring range of 30 to 210. Higher scores indicate more impairment.	Baseline and Day 5
Secondary	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 5: 70 mg	The PANSS is a validated measure that evaluates the presence, absence, and severity of 30 symptoms of schizophrenia including both positive and negative symptoms and general psychopathology. Each of the 30-items are rated on a scale of 1 (absent) to 7 (extreme) with a total scoring range of 30 to 210. Higher scores indicate more impairment.	Baseline and Day 5
Secondary	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 5: 100 mg	The PANSS is a validated measure that evaluates the presence, absence, and severity of 30 symptoms of schizophrenia including both positive and negative symptoms and general psychopathology. Each of the 30-items are rated on a scale of 1 (absent) to 7 (extreme) with a total scoring range of 30 to 210. Higher scores indicate more impairment.	Baseline and Day 5
Secondary	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 5: 150 mg	The PANSS is a validated measure that evaluates the presence, absence, and severity of 30 symptoms of schizophrenia including both positive and negative symptoms and general psychopathology. Each of the 30-items are rated on a scale of 1 (absent) to 7 (extreme) with a total scoring range of 30 to 210. Higher scores indicate more impairment.	Baseline and Day 5
Secondary	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 5: 200 mg	The PANSS is a validated measure that evaluates the presence, absence, and severity of 30 symptoms of schizophrenia including both positive and negative symptoms and general psychopathology. Each of the 30-items are rated on a scale of 1 (absent) to 7 (extreme) with a total scoring range of 30 to 210. Higher scores indicate more impairment.	Baseline and Day 5
Secondary	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 5: 250 mg	The PANSS is a validated measure that evaluates the presence, absence, and severity of 30 symptoms of schizophrenia including both positive and negative symptoms and general psychopathology. Each of the 30-items are rated on a scale of 1 (absent) to 7 (extreme) with a total scoring range of 30 to 210. Higher scores indicate more impairment.	Baseline and Day 5
Secondary	Change From Baseline in Scale for the Assessment of Negative Symptoms (SANS-18) Total Score at Day 5: 50 mg	The SANS was modified by eliminating the global and attention items; the score of the remaining non-global items is referred to as the SANS-18 total score. Each of the 18-items is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 90. Higher scores indicate more impairment.	Baseline and Day 5
Secondary	Change From Baseline in Scale for the Assessment of Negative Symptoms (SANS-18) Total Score at Day 5: 70 mg	The SANS was modified by eliminating the global and attention items; the score of the remaining non-global items is referred to as the SANS-18 total score. Each of the 18-items is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 90. Higher scores indicate more impairment.	Baseline and Day 5
Secondary	Change From Baseline in Scale for the Assessment of Negative Symptoms (SANS-18) Total Score at Day 5: 100 mg	The SANS was modified by eliminating the global and attention items; the score of the remaining non-global items is referred to as the SANS-18 total score. Each of the 18-items is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 90. Higher scores indicate more impairment.	Baseline and Day 5
Secondary	Change From Baseline in Scale for the Assessment of Negative Symptoms (SANS-18) Total Score at Day 5: 150 mg	The SANS was modified by eliminating the global and attention items; the score of the remaining non-global items is referred to as the SANS-18 total score. Each of the 18-items is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 90. Higher scores indicate more impairment.	Baseline and Day 5
Secondary	Change From Baseline in Scale for the Assessment of Negative Symptoms (SANS-18) Total Score at Day 5: 200 mg	The SANS was modified by eliminating the global and attention items; the score of the remaining non-global items is referred to as the SANS-18 total score. Each of the 18-items is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 90. Higher scores indicate more impairment.	Baseline and Day 5
Secondary	Change From Baseline in Scale for the Assessment of Negative Symptoms (SANS-18) Total Score at Day 5: 250 mg	The SANS was modified by eliminating the global and attention items; the score of the remaining non-global items is referred to as the SANS-18 total score. Each of the 18-items is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 90. Higher scores indicate more impairment.	Baseline and Day 5
Secondary	Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Total Score at Day 5: 50 mg	CDSS is a 9-item scale to evaluate depression in subjects who have schizophrenia rated from 0 (absence of symptoms) to 3 (severe symptoms) with a total score range of 0 to 27. Lower scores indicate less depression.	Baseline and Day 5
Secondary	Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Total Score at Day 5: 70 mg	CDSS is a 9-item scale to evaluate depression in subjects who have schizophrenia rated from 0 (absence of symptoms) to 3 (severe symptoms) with a total score range of 0 to 27. Lower scores indicate less depression.	Baseline and Day 5
Secondary	Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Total Score at Day 5: 100 mg	CDSS is a 9-item scale to evaluate depression in subjects who have schizophrenia rated from 0 (absence of symptoms) to 3 (severe symptoms) with a total score range of 0 to 27. Lower scores indicate less depression.	Baseline and Day 5
Secondary	Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Total Score at Day 5: 150 mg	CDSS is a 9-item scale to evaluate depression in subjects who have schizophrenia rated from 0 (absence of symptoms) to 3 (severe symptoms) with a total score range of 0 to 27. Lower scores indicate less depression.	Baseline and Day 5
Secondary	Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Total Score at Day 5: 200 mg	CDSS is a 9-item scale to evaluate depression in subjects who have schizophrenia rated from 0 (absence of symptoms) to 3 (severe symptoms) with a total score range of 0 to 27. Lower scores indicate less depression.	Baseline and Day 5
Secondary	Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Total Score at Day 5: 250 mg	CDSS is a 9-item scale to evaluate depression in subjects who have schizophrenia rated from 0 (absence of symptoms) to 3 (severe symptoms) with a total score range of 0 to 27. Lower scores indicate less depression.	Baseline and Day 5
Secondary	Change From Baseline in Simpson Angus Scale (SAS) Total Score at Day 5: 50 mg	SAS is a 10-item scale used to evaluate the presence and severity of extrapyramidal symptoms. The items are scored on a scale from 0 to 4 with item-specific definitions given for each point. Total scores range from 0 to 40. Lower scores indicate less impairment.	Baseline and Day 5
Secondary	Change From Baseline in Simpson Angus Scale (SAS) Total Score at Day 5: 70 mg	SAS is a 10-item scale used to evaluate the presence and severity of extrapyramidal symptoms. The items are scored on a scale from 0 to 4 with item-specific definitions given for each point. Total scores range from 0 to 40. Lower scores indicate less impairment.	Baseline and Day 5
Secondary	Change From Baseline in Simpson Angus Scale (SAS) Total Score at Day 5: 100 mg	SAS is a 10-item scale used to evaluate the presence and severity of extrapyramidal symptoms. The items are scored on a scale from 0 to 4 with item-specific definitions given for each point. Total scores range from 0 to 40. Lower scores indicate less impairment.	Baseline and Day 5
Secondary	Change From Baseline in Simpson Angus Scale (SAS) Total Score at Day 5: 150 mg	SAS is a 10-item scale used to evaluate the presence and severity of extrapyramidal symptoms. The items are scored on a scale from 0 to 4 with item-specific definitions given for each point. Total scores range from 0 to 40. Lower scores indicate less impairment.	Baseline and Day 5
Secondary	Change From Baseline in Simpson Angus Scale (SAS) Total Score at Day 5: 200 mg	SAS is a 10-item scale used to evaluate the presence and severity of extrapyramidal symptoms. The items are scored on a scale from 0 to 4 with item-specific definitions given for each point. Total scores range from 0 to 40. Lower scores indicate less impairment.	Baseline and Day 5
Secondary	Change From Baseline in Simpson Angus Scale (SAS) Total Score at Day 5: 250 mg	SAS is a 10-item scale used to evaluate the presence and severity of extrapyramidal symptoms. The items are scored on a scale from 0 to 4 with item-specific definitions given for each point. Total scores range from 0 to 40. Lower scores indicate less impairment.	Baseline and Day 5
Secondary	Change From Baseline in Barnes Akathisia Scale (BAS) Total Score at Day 5: 50 mg	BAS scale has objective, subjective, and global impression components of akathisia (motor restlessness that manifests itself with an inability to sit still or remain motionless). Objective and subjective components are rated on a scale from 0 (normal/absence) to 3 (severe) and are summed yielding a total score of 0 to 9. Global impression is rated on a scale from 0 (absent) to 5 (severe) with a total score ranging from 0 to 5. Lower scores indicate reduced restlessness.	Baseline and Day 5
Secondary	Change From Baseline in Barnes Akathisia Scale (BAS) Total Score at Day 5: 70 mg	BAS scale has objective, subjective, and global impression components of akathisia (motor restlessness that manifests itself with an inability to sit still or remain motionless). Objective and subjective components are rated on a scale from 0 (normal/absence) to 3 (severe) and are summed yielding a total score of 0 to 9. Global impression is rated on a scale from 0 (absent) to 5 (severe) with a total score ranging from 0 to 5. Lower scores indicate reduced restlessness.	Baseline and Day 5
Secondary	Change From Baseline in Barnes Akathisia Scale (BAS) Total Score at Day 5: 100 mg	BAS scale has objective, subjective, and global impression components of akathisia (motor restlessness that manifests itself with an inability to sit still or remain motionless). Objective and subjective components are rated on a scale from 0 (normal/absence) to 3 (severe) and are summed yielding a total score of 0 to 9. Global impression is rated on a scale from 0 (absent) to 5 (severe) with a total score ranging from 0 to 5. Lower scores indicate reduced restlessness.	Baseline and Day 5
Secondary	Change From Baseline in Barnes Akathisia Scale (BAS) Total Score at Day 5: 150 mg	BAS scale has objective, subjective, and global impression components of akathisia (motor restlessness that manifests itself with an inability to sit still or remain motionless). Objective and subjective components are rated on a scale from 0 (normal/absence) to 3 (severe) and are summed yielding a total score of 0 to 9. Global impression is rated on a scale from 0 (absent) to 5 (severe) with a total score ranging from 0 to 5. Lower scores indicate reduced restlessness.	Baseline and Day 5
Secondary	Change From Baseline in Barnes Akathisia Scale (BAS) Total Score at Day 5: 200 mg	BAS scale has objective, subjective, and global impression components of akathisia (motor restlessness that manifests itself with an inability to sit still or remain motionless). Objective and subjective components are rated on a scale from 0 (normal/absence) to 3 (severe) and are summed yielding a total score of 0 to 9. Global impression is rated on a scale from 0 (absent) to 5 (severe) with a total score ranging from 0 to 5. Lower scores indicate reduced restlessness.	Baseline and Day 5
Secondary	Change From Baseline in Barnes Akathisia Scale (BAS) Total Score at Day 5: 250 mg	BAS scale has objective, subjective, and global impression components of akathisia (motor restlessness that manifests itself with an inability to sit still or remain motionless). Objective and subjective components are rated on a scale from 0 (normal/absence) to 3 (severe) and are summed yielding a total score of 0 to 9. Global impression is rated on a scale from 0 (absent) to 5 (severe) with a total score ranging from 0 to 5. Lower scores indicate reduced restlessness.	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: Groton Maze Learning Test, 50 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: Groton Maze Learning Test, 70 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: Groton Maze Learning Test, 100 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: Groton Maze Learning Test, 150 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: Groton Maze Learning Test, 200 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: Groton Maze Learning Test, 250 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: Detection Task, 50 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: Detection Task, 70 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: Detection Task, 100 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: Detection Task, 150 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: Detection Task, 200 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: Detection Task, 250 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: Identification Task, 50 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: Identification Task, 70 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: Identification Task, 100 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: Identification Task, 150 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: Identification Task, 200 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: Identification Task, 250 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: One Card Learning Task, 50 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: One Card Learning Task, 70 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: One Card Learning Task, 100 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: One Card Learning Task, 150 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: One Card Learning Task, 200 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5
Secondary	Change From Baseline in Cognitive Test Battery (CogState Battery) Score at Day 5: One Card Learning Task, 250 mg	This battery is a series of 4 computerized cognition tests (Groton Maze Learning Test, Detection Task, Identification Task, and One Card Learning Task) designed to measure reaction time, visual learning and reasoning, and problem solving. The entire battery takes approximately 12 minutes to complete. CogState scores are measured on a linear scale (no maximum score). The Groton Maze Learning Test measures total number of errors made in problem solving (lower score = better performance). The Detection Task is measured by speed of performance (lower score = better performance). The Identification Task is measured by speed of performance (lower score = better performance). One Card Learning Task measures the accuracy of performance (higher score = better performance).	Baseline and Day 5