Trial Outcomes & Findings for Efficacy, Safety, and Tolerability of SPD489 in Adults With Schizophrenia and Predominant Negative Symptoms (NCT NCT00922272)

Last Updated: 2021-06-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

92 participants

Primary outcome timeframe

Open-label Baseline and Week 10 Open-label Phase

Results posted on

2021-06-09

Participant Flow

The study consisted of a 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20 to 70 mg of SPD489 (Lisdexamfetamine dimesylate) once-daily. They were then randomized into the Double-Blind Phase receiving either their optimal dose of SPD489 or placebo once-daily for 4 weeks.

Participant milestones

Participant milestones
Measure	SPD489 The study consisted of a 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication. They were then randomized into the Double-Blind Phase receiving either their optimal dose of adjunctive SPD489 or placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.	Placebo Subjects received placebo once-daily for 4 weeks during the Double-blind Phase to a stable dose of atypical antipsychotic medication.
Open-label Phase STARTED	92	0
Open-label Phase COMPLETED	69	0
Open-label Phase NOT COMPLETED	23	0
Double-blind Phase STARTED	34	35
Double-blind Phase COMPLETED	27	29
Double-blind Phase NOT COMPLETED	7	6

Reasons for withdrawal

Reasons for withdrawal
Measure	SPD489 The study consisted of a 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication. They were then randomized into the Double-Blind Phase receiving either their optimal dose of adjunctive SPD489 or placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.	Placebo Subjects received placebo once-daily for 4 weeks during the Double-blind Phase to a stable dose of atypical antipsychotic medication.
Open-label Phase Adverse Event	5	0
Open-label Phase Protocol Violation	1	0
Open-label Phase Withdrawal by Subject	11	0
Open-label Phase Failure to meet randomization criteria	1	0
Open-label Phase Withdrawal criteria met	5	0
Double-blind Phase Adverse Event	1	1
Double-blind Phase Withdrawal by Subject	1	1
Double-blind Phase Lost to Follow-up	2	1
Double-blind Phase Withdrawal criteria met	1	1
Double-blind Phase Noncompliance	1	1
Double-blind Phase Positive urine drug screen	1	1

Baseline Characteristics

Efficacy, Safety, and Tolerability of SPD489 in Adults With Schizophrenia and Predominant Negative Symptoms

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall n=92 Participants Constitutes all subjects contained in the Safety Analysis Set defined as all subjects who took at least 1 dose of open-label investigational product and for whom at least 1 follow-up safety assessment was made.
Age, Continuous	42.3 years STANDARD_DEVIATION 9.11 • n=5 Participants
Age, Customized <18 years	0 Participants n=5 Participants
Age, Customized Between 18 and 55 years	92 Participants n=5 Participants
Age, Customized >55 years	0 Participants n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants
Sex: Female, Male Male	62 Participants n=5 Participants
Region of Enrollment United States	92 Participants n=5 Participants

PRIMARY outcome

Timeframe: Open-label Baseline and Week 10 Open-label Phase

Population: Open-label Phase Full Analysis Set (FAS) defined as all enrolled subjects who took at least 1 dose of the investigational product and had 1 primary efficacy assessment after baseline in the Open-label Phase.

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=92 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Open-label Baseline in Modified Scale for the Assessment of Negative Symptoms (SANS-18) Total Score at Week 10 Open-label Phase, Last Observation Carried Forward (LOCF)	-12.9 Units on a scale Standard Deviation 10.04	—

PRIMARY outcome

Timeframe: Double-blind Randomization Baseline and Week 4 Double-blind Phase

Population: Randomized Evaluable Set (RES) defined as all randomized subjects who were responders (Response is defined as reduction in total SANS score of greater than or equal to 20%) at the Double-blind Randomization and had SANS-18 total scores at week 4 of the Double-blind Phase or the early termination visit.

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=15 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) n=20 Participants Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Double-blind Randomization Baseline in SANS-18 Total Score at Week 4 Double-blind Phase, Termination Observation Carried Forward (TOCF)	4.5 Units on a scale Standard Error 2.14	2.2 Units on a scale Standard Error 1.85

SECONDARY outcome

Timeframe: Week 10 Open-label Phase

Population: FAS

Response is defined as reduction in total SANS score of greater than or equal to 20%. 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.

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=70 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Percent of Participants In Open-label Phase Who Were SANS-18 Responders at Week 10 Open-label Phase	52.9 Percent of participants	—

SECONDARY outcome

Timeframe: Week 4 Double-blind Phase

Population: RES

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=14 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) n=17 Participants Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Percent of Participants In Double-blind Phase Who Maintained SANS-18 Response at Week 4 Double-blind Phase	71.4 Percent of participants	82.4 Percent of participants

SECONDARY outcome

Timeframe: Open-label Baseline and Week 10 Open-label Phase

Population: FAS

The SANS assesses 5 symptom complexes to rate the negative symptoms of subjects. 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.

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=70 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Open-label Baseline in SANS Global Scores at Week 10 Open-label Phase Affective Flattening	-0.9 Units on a scale Standard Deviation 0.80	—
Change From Open-label Baseline in SANS Global Scores at Week 10 Open-label Phase Alogia	-0.9 Units on a scale Standard Deviation 0.65	—
Change From Open-label Baseline in SANS Global Scores at Week 10 Open-label Phase Avolition-Apathy	-0.5 Units on a scale Standard Deviation 0.81	—
Change From Open-label Baseline in SANS Global Scores at Week 10 Open-label Phase Anhedonia-Asociality	-0.7 Units on a scale Standard Deviation 0.77	—
Change From Open-label Baseline in SANS Global Scores at Week 10 Open-label Phase Attention	-0.7 Units on a scale Standard Deviation 0.80	—

SECONDARY outcome

Timeframe: Double-blind Randomization Baseline and Week 4 Double-blind Phase

Population: RES

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=14 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) n=17 Participants Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Double-blind Randomization Baseline in SANS Global Scores at Week 4 Double-blind Phase Affective Flattening	0.2 Units on a scale Standard Error 0.17	0.2 Units on a scale Standard Error 0.15
Change From Double-blind Randomization Baseline in SANS Global Scores at Week 4 Double-blind Phase Alogia	0.5 Units on a scale Standard Error 0.21	0.0 Units on a scale Standard Error 0.19
Change From Double-blind Randomization Baseline in SANS Global Scores at Week 4 Double-blind Phase Avolition-Apathy	0.2 Units on a scale Standard Error 0.16	0.1 Units on a scale Standard Error 0.15
Change From Double-blind Randomization Baseline in SANS Global Scores at Week 4 Double-blind Phase Anhedonia-Asociality	0.3 Units on a scale Standard Error 0.18	0.1 Units on a scale Standard Error 0.16
Change From Double-blind Randomization Baseline in SANS Global Scores at Week 4 Double-blind Phase Attention	0.4 Units on a scale Standard Error 0.18	0.3 Units on a scale Standard Error 0.17

SECONDARY outcome

Timeframe: Open-label Baseline and Week 10 Open-label Phase

Population: FAS

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.

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=92 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Open-label Baseline in Positive and Negative Syndrome Scale (PANSS) Scores at Week 10 Open-label Phase, LOCF Positive subscale	-1.0 Units on a scale Standard Deviation 2.23	—
Change From Open-label Baseline in Positive and Negative Syndrome Scale (PANSS) Scores at Week 10 Open-label Phase, LOCF Negative subscale	-4.8 Units on a scale Standard Deviation 4.01	—
Change From Open-label Baseline in Positive and Negative Syndrome Scale (PANSS) Scores at Week 10 Open-label Phase, LOCF General Psychopathology subscale	-4.0 Units on a scale Standard Deviation 5.11	—

SECONDARY outcome

Timeframe: Double-blind Randomization Baseline and Week 4 Double-blind Phase

Population: Randomized FAS defined as all subjects who received randomized investigational product and had a SANS-18 total scores at week 4 or at the early termination visit.

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=34 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) n=35 Participants Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Double-blind Randomization Baseline in PANSS Scores at Week 4 Double-blind Phase, TOCF Positive subscale	0.5 Units on a scale Standard Error 0.31	-0.1 Units on a scale Standard Error 0.31
Change From Double-blind Randomization Baseline in PANSS Scores at Week 4 Double-blind Phase, TOCF Negative subscale	0.9 Units on a scale Standard Error 0.46	-0.1 Units on a scale Standard Error 0.45
Change From Double-blind Randomization Baseline in PANSS Scores at Week 4 Double-blind Phase, TOCF General Psychopathology subscale	0.9 Units on a scale Standard Error 0.78	-0.9 Units on a scale Standard Error 0.77

SECONDARY outcome

Timeframe: Open-label Baseline

Population: FAS

CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=92 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline Normal, not at all ill	0 Percent of participants	—
Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline Borderline mentally ill	0 Percent of participants	—
Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline Mildly ill	29.3 Percent of participants	—
Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline Moderately ill	55.4 Percent of participants	—
Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline Markedly ill	14.1 Percent of participants	—
Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline Severely ill	1.1 Percent of participants	—
Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline Among the most extremely ill	0 Percent of participants	—

SECONDARY outcome

Timeframe: Week 10 Open-label Phase

Population: FAS

CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=70 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Percent of Participants With CGI-S at Week 10 Open-label Phase Normal, not at all ill	0 Percent of participants	—
Percent of Participants With CGI-S at Week 10 Open-label Phase Borderline mentally ill	2.9 Percent of participants	—
Percent of Participants With CGI-S at Week 10 Open-label Phase Mildly ill	54.3 Percent of participants	—
Percent of Participants With CGI-S at Week 10 Open-label Phase Moderately ill	38.6 Percent of participants	—
Percent of Participants With CGI-S at Week 10 Open-label Phase Markedly ill	4.3 Percent of participants	—
Percent of Participants With CGI-S at Week 10 Open-label Phase Severely ill	0 Percent of participants	—
Percent of Participants With CGI-S at Week 10 Open-label Phase Among the most extremely ill	0 Percent of participants	—

SECONDARY outcome

Timeframe: Double-blind Randomization Baseline

Population: Randomized FAS

CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=34 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) n=35 Participants Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Percent of Participants With CGI-S at Double-blind Randomization Baseline Normal, not at all ill	0 Percent of participants	0 Percent of participants
Percent of Participants With CGI-S at Double-blind Randomization Baseline Borderline mentally ill	2.9 Percent of participants	2.9 Percent of participants
Percent of Participants With CGI-S at Double-blind Randomization Baseline Mildly ill	50.0 Percent of participants	60.0 Percent of participants
Percent of Participants With CGI-S at Double-blind Randomization Baseline Moderately ill	38.2 Percent of participants	37.1 Percent of participants
Percent of Participants With CGI-S at Double-blind Randomization Baseline Markedly ill	8.8 Percent of participants	0 Percent of participants
Percent of Participants With CGI-S at Double-blind Randomization Baseline Severely ill	0 Percent of participants	0 Percent of participants
Percent of Participants With CGI-S at Double-blind Randomization Baseline Among the most extremely ill	0 Percent of participants	0 Percent of participants

SECONDARY outcome

Timeframe: Week 4 Double-blind Phase

Population: Randomized FAS

CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=29 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) n=29 Participants Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Percent of Participants With CGI-S at Week 4 Double-blind Phase Normal, not at all ill	0 Percent of participants	0 Percent of participants
Percent of Participants With CGI-S at Week 4 Double-blind Phase Borderline mentally ill	3.4 Percent of participants	13.8 Percent of participants
Percent of Participants With CGI-S at Week 4 Double-blind Phase Mildly ill	34.5 Percent of participants	69.0 Percent of participants
Percent of Participants With CGI-S at Week 4 Double-blind Phase Moderately ill	48.3 Percent of participants	13.8 Percent of participants
Percent of Participants With CGI-S at Week 4 Double-blind Phase Markedly ill	13.8 Percent of participants	3.4 Percent of participants
Percent of Participants With CGI-S at Week 4 Double-blind Phase Severely ill	0 Percent of participants	0 Percent of participants
Percent of Participants With CGI-S at Week 4 Double-blind Phase Among the most extremely ill	0 Percent of participants	0 Percent of participants

SECONDARY outcome

Timeframe: Open-label Phase Week 10

Population: FAS

CGI-C permits a global evaluation of the change of the subject's overall schizophrenia condition over time. It 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

Outcome measures
Measure	SPD489 (Open-label Phase) n=70 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Percent of Participants With Improvement on Clinical Global Impression - Change (CGI-C) at Week 10 Open-label Phase	30.0 Percent of participants	—

SECONDARY outcome

Timeframe: Double-blind Phase Week 4

Population: Randomized FAS

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=29 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) n=29 Participants Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Percent of Participants With Improvement on CGI-C at Week 4 Double-blind Phase	17.2 Percent of participants	27.6 Percent of participants

SECONDARY outcome

Timeframe: Open-label Baseline and week 10 Open-label Phase

Population: FAS

BACS measures attention and speed of processing, and the test score is the total number correct. The measure of the test is the number of correct numerals where subjects write numerals 1-9 as matches to nonmeaningful symbols on a response sheet for 90 seconds, based upon a key provided to them.

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=73 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Open-label Baseline in the Brief Assessment of Cognition in Schizophrenia (BACS) Total Score at Week 10 Open-label Phase	2.3 correct numerals Standard Deviation 8.92	—

SECONDARY outcome

Timeframe: Double-blind Randomization Baseline and Week 4

Population: Randomized FAS

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=32 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) n=31 Participants Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Double-blind Randomization Baseline in BACS Total Score at Week 4 Double-blind Phase	0.1 correct numerals Standard Error 1.19	-2.7 correct numerals Standard Error 1.21

SECONDARY outcome

Timeframe: Open-label Baseline and week 10 Open-label Phase

Population: FAS

LNS is a test of verbal working memory. Subjects are presented with a sequence of numbers and letters aurally and then asked to tell the rater the numbers first from lowest to highest followed by the letters in alphabetical sequence. The measure is the number of correct sequences.

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=73 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Open-label Baseline in Letter-Number Span Test (LNS) Total Score at Week 10 Open-label Phase	0.8 correct sequences Standard Deviation 7.72	—

SECONDARY outcome

Timeframe: Double-blind Randomization Baseline and Week 4

Population: Randomized FAS

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=32 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) n=31 Participants Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Double-blind Randomization Baseline in LNS Total Score at Week 4 Double-blind Phase	-0.1 correct sequences Standard Error 1.26	1.3 correct sequences Standard Error 1.28

SECONDARY outcome

Timeframe: Open-label Baseline and Week 10

Population: FAS

HVLT-R measures verbal learning. Test scores are the total number of words recalled correctly over 3 trials. The test consists of 12 nouns read aloud for 3 consecutive trials and each trial is followed by a recall test.

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=73 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Open-label Baseline in Hopkins Verbal Learning Test - Revised (HVLT-R) Total Score at Week 10 Open-label Phase	0.7 words recalled Standard Deviation 7.54	—

SECONDARY outcome

Timeframe: Double-blind Randomization Baseline and week 4 Double-blind Phase

Population: Randomized FAS

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=31 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) n=31 Participants Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Double-blind Randomization Baseline in HVLT-R Total Scores at Week 4 Double-blind Phase	-1.5 words recalled Standard Error 1.01	1.0 words recalled Standard Error 1.01

SECONDARY outcome

Timeframe: Open-label Baseline and week 10 Open-label Phase

Population: FAS

UPSA-B assesses skills in 5 areas of life functioning. It contains 2 subscales. Percentages correct on these 2 subscales are multiplied by 50. Thus, scores can range from 0 to 50 on each of these 2 subscales, and total scores can range from 0 to 100. Scores of 75 or higher are associated with independent living.

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=83 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Open-label Baseline in University of California Performance-Based Skills Assessment, Brief Version (UPSA-B) Scores at Week 10 Open-label Phase, LOCF Total Skills	6.2 Scores on a scale Standard Deviation 12.20	—
Change From Open-label Baseline in University of California Performance-Based Skills Assessment, Brief Version (UPSA-B) Scores at Week 10 Open-label Phase, LOCF Communication Skills	3.7 Scores on a scale Standard Deviation 8.56	—
Change From Open-label Baseline in University of California Performance-Based Skills Assessment, Brief Version (UPSA-B) Scores at Week 10 Open-label Phase, LOCF Financial Skills	2.5 Scores on a scale Standard Deviation 7.45	—

SECONDARY outcome

Timeframe: Double-blind Randomization Baseline and Week 4 Double-blind Phase

Population: Randomized FAS

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=32 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) n=31 Participants Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Double-blind Randomization Baseline in UPSA-B Scores at Week 4 Double-blind Phase Total Skills	-1.5 Scores on a scale Standard Error 1.35	0.0 Scores on a scale Standard Error 1.37
Change From Double-blind Randomization Baseline in UPSA-B Scores at Week 4 Double-blind Phase Communication Skills	-1.5 Scores on a scale Standard Error 1.14	-0.6 Scores on a scale Standard Error 1.16
Change From Double-blind Randomization Baseline in UPSA-B Scores at Week 4 Double-blind Phase Financial Skills	-0.3 Scores on a scale Standard Error 0.83	0.9 Scores on a scale Standard Error 0.84

SECONDARY outcome

Timeframe: Open-label Baseline and Week 10 Open-label Phase

Population: FAS

BRIEF-A is a validated 75-item questionnaire composed of three indexes (Global Executive Composite, Behavioral Recognition Index, and Metacognition Index). Items are rated 1 (never), 2 (sometimes), and 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=70 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Open-label Baseline in Behavioral Rating Inventory of Executive Function - Adult Version (BRIEF-A) T-scores at Week 10 Open-label Phase Global Executive Composite	-3.9 T-scores Standard Deviation 13.29	—
Change From Open-label Baseline in Behavioral Rating Inventory of Executive Function - Adult Version (BRIEF-A) T-scores at Week 10 Open-label Phase Behavioral Recognition Index	-3.1 T-scores Standard Deviation 12.89	—
Change From Open-label Baseline in Behavioral Rating Inventory of Executive Function - Adult Version (BRIEF-A) T-scores at Week 10 Open-label Phase Metacognition Index	-3.9 T-scores Standard Deviation 13.12	—

SECONDARY outcome

Timeframe: Double-blind Randomization Baseline and Week 4 Double-blind Phase

Population: Randomized FAS

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=29 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) n=33 Participants Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Double-blind Randomization Baseline in BRIEF-A T-Scores at Week 4 Double-blind Phase Global Executive Composite	-1.7 T-scores Standard Error 1.19	-1.2 T-scores Standard Error 1.12
Change From Double-blind Randomization Baseline in BRIEF-A T-Scores at Week 4 Double-blind Phase Behavioral Recognition Index	-0.9 T-scores Standard Error 1.22	-1.6 T-scores Standard Error 1.14
Change From Double-blind Randomization Baseline in BRIEF-A T-Scores at Week 4 Double-blind Phase Metacognition Index	-2.0 T-scores Standard Error 1.26	-0.7 T-scores Standard Error 1.18

SECONDARY outcome

Timeframe: Open-label Baseline and Week 10 Open-label Phase

Population: SAS

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.

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=70 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Open-label Baseline in Simpson Angus Scale (SAS) Total Score at Week 10 Open-label Phase	-0.01 Units on a scale Standard Deviation 0.063	—

SECONDARY outcome

Timeframe: Open-label Baseline and Week 4 Double-blind Phase

Population: Randomized SAS

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=32 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) n=33 Participants Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Open-label Baseline in SAS Total Score at Week 4 of Double-blind Phase	0.00 Units on a scale Standard Deviation 0.093	0.00 Units on a scale Standard Deviation 0.043

SECONDARY outcome

Timeframe: Open-label Baseline and week 10 Open-label Phase

Population: SAS

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.

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=70 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Open-label Baseline in Barnes Akathisia Scale (BAS) Scores at Week 10 Open-label Phase Objective	0.0 Units on a scale Standard Deviation 0.17	—
Change From Open-label Baseline in Barnes Akathisia Scale (BAS) Scores at Week 10 Open-label Phase Subjective	0.0 Units on a scale Standard Deviation 0.56	—
Change From Open-label Baseline in Barnes Akathisia Scale (BAS) Scores at Week 10 Open-label Phase Global	0.0 Units on a scale Standard Deviation 0.36	—

SECONDARY outcome

Timeframe: Open-label Baseline and Week 4 Double-blind Phase

Population: Randomized SAS

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=32 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) n=33 Participants Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Open-label Baseline in BAS Scores at Week 4 of Double-blind Phase Objective	0.0 Units on a scale Standard Deviation 0.18	-0.1 Units on a scale Standard Deviation 0.24
Change From Open-label Baseline in BAS Scores at Week 4 of Double-blind Phase Subjective	0.0 Units on a scale Standard Deviation 0.31	-0.1 Units on a scale Standard Deviation 0.65
Change From Open-label Baseline in BAS Scores at Week 4 of Double-blind Phase Global	0.0 Units on a scale Standard Deviation 0.18	-0.2 Units on a scale Standard Deviation 0.44

SECONDARY outcome

Timeframe: Open-label Baseline and Week 10 Open-label Phase

Population: SAS

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

Outcome measures
Measure	SPD489 (Open-label Phase) n=85 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Open-label Baseline in Amphetamine Cessation Symptom Assessment (ACSA) Total Score at Week 10 Open-label Phase	-1.8 Units on a scale Standard Deviation 9.69	—

SECONDARY outcome

Timeframe: Double-blind Randomization Baseline and Week 4 Double-blind Phase

Population: Randomized SAS

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

Outcome measures
Measure	SPD489 (Open-label Phase) n=29 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) n=29 Participants Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Double-blind Randomization Baseline in ACSA Total Score at Week 4 Double-blind Phase	0.4 Units on a scale Standard Deviation 7.65	-2.9 Units on a scale Standard Deviation 8.75

SECONDARY outcome

Timeframe: Open-label Baseline and Week 10 Open-label Phase

Population: SAS

PSQI evaluates 7 areas of quality and pattern of sleep. Each area is rated on a scale from 0 (better) to 3 (worse) with a total score ranging from 0 to 21. Reduction in total scores are associated with better sleep quality.

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=69 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Open-label Baseline in Pittsburgh Sleep Quality Index (PSQI) Total Global Score at Week 10 Open-label Phase	-0.7 Units on a scale Standard Deviation 3.15	—

SECONDARY outcome

Timeframe: Open-label Baseline and Week 4 Double-blind Phase

Population: Randomized SAS

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=32 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) n=32 Participants Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Open-label Baseline in PSQI Total Global Score at Week 4 of Double-blind Phase	0.3 Units on a scale Standard Deviation 3.01	-1.7 Units on a scale Standard Deviation 3.00

SECONDARY outcome

Timeframe: Open-label Baseline and Week 10 Open-label Phase

Population: Safety Analysis Set (SAS) defined as all subjects who took at least 1 dose of open-label investigational product and for whom at least 1 follow-up safety assessment was made.

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.

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=70 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Open-label Baseline in Calgary Depression Scale for Schizophrenia (CDSS) at Week 10 Open-label Phase	-0.7 Units on a scale Standard Deviation 2.11	—

SECONDARY outcome

Timeframe: Open-label Baseline and Week 4 of Double-blind Phase

Population: Randomized SAS defined as all subjects who took at least 1 dose of randomized investigational product and for whom at least 1 follow-up safety assessment was made.

Outcome measures

Outcome measures
Measure	SPD489 (Open-label Phase) n=32 Participants A 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication.	Placebo (Double-blind Phase) n=33 Participants Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Change From Open-label Baseline in CDSS at Week 4 of Double-blind Phase	-0.1 Units on a scale Standard Deviation 2.34	-0.7 Units on a scale Standard Deviation 2.30

Adverse Events

SPD489 (Open-label Phase)

Serious events: 3 serious events

Other events: 56 other events

Deaths: 0 deaths

SPD489 (Double-blind Phase)

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo (Double-blind Phase)

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	SPD489 (Open-label Phase) n=92 participants at risk Subjects receive either 20, 30, 40, 50, 60 or 70 mg of SPD489 (Lisdexamfetamine dimesylate) once-daily	SPD489 (Double-blind Phase) n=34 participants at risk Subjects receive either 20, 30, 40, 50, 60 or 70 mg of SPD489 (Lisdexamfetamine dimesylate) once-daily	Placebo (Double-blind Phase) n=35 participants at risk Subjects receive placebo once-daily
Psychiatric disorders Schizophrenia	1.1% 1/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
General disorders Chest pain	1.1% 1/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Psychiatric disorders Hallucination	1.1% 1/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Psychiatric disorders Major depression	1.1% 1/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Gastrointestinal disorders Dyspepsia	0.00% 0/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.

Other adverse events

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

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

Measure	SPD489 (Open-label Phase) n=92 participants at risk Subjects receive either 20, 30, 40, 50, 60 or 70 mg of SPD489 (Lisdexamfetamine dimesylate) once-daily	SPD489 (Double-blind Phase) n=34 participants at risk Subjects receive either 20, 30, 40, 50, 60 or 70 mg of SPD489 (Lisdexamfetamine dimesylate) once-daily	Placebo (Double-blind Phase) n=35 participants at risk Subjects receive placebo once-daily
Gastrointestinal disorders Diarrhea	5.4% 5/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Gastrointestinal disorders Dry Mouth	6.5% 6/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Metabolism and nutrition disorders Decreased Appetite	10.9% 10/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Nervous system disorders Dizziness	8.7% 8/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Nervous system disorders Headache	14.1% 13/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	5.9% 2/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	5.7% 2/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Psychiatric disorders Insomnia	10.9% 10/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Gastrointestinal disorders Nausea	2.2% 2/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	5.9% 2/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
General disorders Fatigue	4.3% 4/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	5.9% 2/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Gastrointestinal disorders Abdominal distention	2.2% 2/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Gastrointestinal disorders Abdominal pain upper	2.2% 2/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Gastrointestinal disorders Dyspepsia	3.3% 3/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Gastrointestinal disorders Vomiting	4.3% 4/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
General disorders Nasopharyngitis	2.2% 2/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Injury, poisoning and procedural complications Skin laceration	2.2% 2/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Investigations Weight decreased	2.2% 2/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Investigations Weight increased	3.3% 3/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Metabolism and nutrition disorders Anorexia	2.2% 2/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Metabolism and nutrition disorders Increased appetite	3.3% 3/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Musculoskeletal and connective tissue disorders Back pain	2.2% 2/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Nervous system disorders Sedation	2.2% 2/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Nervous system disorders Somnolence	3.3% 3/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Psychiatric disorders Agitation	3.3% 3/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Psychiatric disorders Anxiety	4.3% 4/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Psychiatric disorders Depressed mood	4.3% 4/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Respiratory, thoracic and mediastinal disorders Cough	4.3% 4/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Respiratory, thoracic and mediastinal disorders Rhinorrhea	4.3% 4/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Skin and subcutaneous tissue disorders Rash erythematous	2.2% 2/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Gastrointestinal disorders Stomach discomfort	0.00% 0/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
General disorders Hernia	0.00% 0/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
General disorders Irritability	0.00% 0/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Infections and infestations Influenza	0.00% 0/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Injury, poisoning and procedural complications Animal bite	0.00% 0/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Investigations Blood pressure diastolic increased	0.00% 0/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Investigations Blood prolactin increased	0.00% 0/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Investigations Electrocardiogram T wave abnormal	0.00% 0/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Nervous system disorders Aphasia	0.00% 0/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Nervous system disorders Migraine	0.00% 0/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Psychiatric disorders Restlessness	0.00% 0/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Psychiatric disorders Schizophrenia	0.00% 0/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
Reproductive system and breast disorders Menstruation irregular	0.00% 0/92 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	0.00% 0/34 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.	2.9% 1/35 Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.