Asenapine in the Treatment of Older Adults With Bipolar Disorder

• Sponsor: University Hospitals Cleveland Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01460290
• Collaborator: Case Western Reserve University (Other)
• Enrollment: 15
• Location: 1
• Arm: 1
• Duration (Months): 29
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Objectives: The investigators propose a first-ever, prospective trial of asenapine in older adults with bipolar disorder (BD) to evaluate effects on mood symptoms, tolerability and functional/general health status. Given the dearth of treatment data on older adults with BD, findings are likely to be of substantial clinical interest, may inform larger future studies and will assist in refining bipolar treatment recommendations.

Hypotheses:

Primary: Asenapine therapy will be associated with reduced bipolar manic and depressive symptoms in older adults with BD.

Secondary: Asenapine therapy will be associated with improved functional and general health status, improved global psychopathology, and good tolerability in older adults with BD.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Drug: Asenapine	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Asenapine in the Treatment of Older Adults With Bipolar Disorder
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Asenapine 12-weeks of open-label asenapine treatment

Drug: Asenapine; Asenapine will be administered open-label in pill form. Asenapine will be initiated at 5 mg twice a day and increased as tolerated to a maximum of 20 mg/day. It is anticipated that maximum stable dosing will be achieved by 4 weeks of treatment, although dosage may be reduced due to tolerability concerns at the discretion of the treating research psychiatrist.; Other Names: Saphris

Outcome Measures

Primary Outcome Measures

1. Change in Depressive Symptoms as Measured by the Hamilton Depression Rating Scale (HAM-D) [Baseline and 12 weeks]

   The minimum possible score is 0 and the maximum score is 52. A higher score implies a worse condition.

2. Change in Manic Symptoms as Measured by the Young Mania Rating Scale (YMRS) [Baseline and 12 weeks]

   The minimum possible score is 0 and the maximum score is 60. A higher score implies a worse condition.

Secondary Outcome Measures

1. Change in Global Psychopathology as Measured by the Clinical Global Impression Scale for Use in Bipolar Illness (CGI-BP) [Baseline and 12 weeks]

   The minimum possible score is 1 and the maximum score is 7. A higher score implies a worse condition. The CGI-BP has three scores - Mania Severity, Depression Severity, and Overall Bipolar Illness Severity.

2. Change in Perception of Physical Health as Measured by the Short Form General Health Survey (SF-12) [Baseline and 12 weeks]

   The minimum possible score is 1 and the maximum score is 99. A higher score implies a better perceived condition.

3. Change in Perception of Mental Health as Measured by the Short Form General Health Survey (SF-12) [Baseline and 12 weeks]

   The minimum possible score is 1 and the maximum score is 99. A higher score implies a better perceived condition.

4. Change in Depressive Symptoms as Measured by the Montgomery Asberg Depression Rating Scale (MADRS) [Baseline and 12 weeks]

   The minimum possible score is 0 and the maximum score is 60. A higher score implies a worse condition.

5. Change in Bipolar Disorder Symptoms as Measured by the Brief Psychiatric Rating Scale (BPRS) [Baseline and 12 weeks]

   The minimum possible score is 18 and the maximum score is 126. A higher score implies a worse condition.

6. Change in Cognitive Status as Measured by the Stroop Task [Baseline and 12 weeks]

   The Stroop evaluates patients for cognitive functioning. Patients are to read words aloud or name colors as quickly as possible in a 45-second period. The measure contains three tasks, each associated with a subscale as follows: Word, Color, and Color-Word. Each subscale contains 100 items. The raw score range for each of the subscales is 0-100. Each raw subscale score is converted to a T-Score. The possible T-Score range for the Word subscale is 15 to 85. The possible T-Score range for the Color subscale is 8 to 92. The possible T-Score range for the Color-Word subscale is 3 to 98. Higher scores on the subscales indicate better cognitive functioning. Subscales are scored independently and are not added to produce a total score.

7. Change in Cognitive Status as Measured by the Trail Making Test [Baseline and 12 weeks]

   The Trails test is a measure of cognitive functioning. The measure consists of two parts: A and B. In part A, participants are asked to draw a trail connecting a series of numbers in sequential order. In Part B, participants are asked to draw a trail connecting a combination of letters and numbers. The time taken to complete each task is noted as the score (e.g., 78 seconds). For Trails A, there is no upper limit on the score, as subjects are given as much time as is needed for them to complete the task. Higher scores indicate poorer cognitive functioning. In Trails B, the task is timed with an upper limit of five minutes. If, at four minutes, it is determined that the subject will not likely complete the task in the time allotted, then the task can be called off. Higher scores indicate poorer cognitive functioning.

8. Change in Cognitive Status as Measured by the Hopkins Verbal Learning Test (HVLT) [Baseline and 12 weeks]

   Evaluates cognitive functioning across domains: recall, delayed recall, retention, recognition (each scored separately). The scores given are titled: recall score, delayed recall score, retention score, recognition discrimination index. Total Recall score = items correctly recalled (0-36). Delayed Recall score = items correctly recalled following delay (0-12). Retention score = percent items recalled that were also recalled after delay (0-100). The Recognition Discrimination score = true positives minus false positives (0-12). Recall task has 12 words and involves to recall of words after all of them are read aloud to the patient. Delayed recall tasks involves the same twelve words, except recall is tasked after a 20-25 minute delay. Recognition task has 24 words. Patient evaluated on how many from original list he or she is able to recognize. Higher scores = better outcomes. Total recall scores appear in this entry below.

9. Change in Cognitive Status as Measured by the Dementia Rating Scale (DRS) [Baseline and 12 weeks]

   The DRS contains items that evaluate cognitive function across 5 subscales: attention, initiation/perseveration, construction, conceptualization, and memory. Subscale raw score ranges are: attention (0-37), initiation/perseveration (0-37), construction (0-6), conceptualization (0-39), and memory (0-25). Raw subscale scores are added for a total raw score with range 0-144. For each raw subscale score, scaled scores are looked up from a battery of 13 tables. Age of the participant determines which table is to be used. Total raw subscale score also has its own scaled score in the tables. In addition to use in determining scaled scores for each of the subscales, these tables are used to look up the scaled score for the total raw score. The tables are contained in the article Robust and Expanded Norms for the Dementia Rating Scale (Pedraza, Lucas, et al. 2010); Archives of Clinical Neuropsychology 25; 347-358. Higher scores, raw and scaled, indicate better cognitive functioning.

10. World Health Organization Disability Assessment Scale (WHO-DAS) [12 weeks]

    The WHO-DAS II is used to assess patients for difficulties that they experience due to health conditions. Six subscales are represented which cover the following domains: Getting Around (range 1-10), Self Care (range 1-10), Life Activities (range 1-20), Understand/Communicate (range 1-10), Participation in Society (range 1-10), and Getting Along with People (range 1-10). Lower scores represent more positive outcomes, while higher scores represent worse outcomes. Total summary scores were not computed for our analyses and is optional for the measure.

11. Barnes Drug-induced Akathisia Rating Scale (BARS) [Baseline and 12 weeks]

    This scale is used to measure the presence of akathisia, as may result from use of certain psychotropic medications. The scale contains four items and the score for each item is added to produce the total score. Total scores range from 0 to 14. Higher scores indicate more adverse outcomes.

12. Assessment of Motor Control Abnormality as Measured by the Simpson Angus Scale (SAS) [Baseline and 12 weeks]

    The Simpson-Angus Scale is used to monitor for neurological and musculoskeletal side effects that may be a result of certain psychotropic medications. The scale consists of 10 questions which each can be rated on a scale of 0 to 4. Scores for each item are added to produce a total score. The highest possible total score is 40. Higher scores indicate more adverse outcomes.

13. Change in Cognitive Status as Measured by the Hopkins Verbal Learning Test (HVLT) [Baseline and 12 weeks]

    Evaluates cognitive functioning across domains: recall, delayed recall, retention, recognition (each scored separately). The scores given are titled: recall score, delayed recall score, retention score, recognition discrimination index. Total Recall score = items correctly recalled (0-12). Delayed Recall score = items correctly recalled following delay (0-12). Retention score = percent items recalled that were also recalled after delay (0-100). The Recognition Discrimination score = true positives minus false positives (0-12). Recall task has 12 words and involves to recall of words after all of them are read aloud to the patient. Delayed recall tasks involves the same twelve words, except recall is tasked after a 20-25 minute delay. Recognition task has 24 words. Patient evaluated on how many from original list he or she is able to recognize. Higher scores = better outcomes. Delayed recall scores appear in this entry below.

14. Change in Cognitive Status as Measured by the Hopkins Verbal Learning Test (HVLT) [Baseline and 12 weeks]

    Evaluates cognitive functioning across domains: recall, delayed recall, retention, recognition (each scored separately). The scores given are titled: recall score, delayed recall score, retention score, recognition discrimination index. Total Recall score = items correctly recalled (0-12). Delayed Recall score = items correctly recalled following delay (0-12). Retention score = percent items recalled that were also recalled after delay (0-100). The Recognition Discrimination score = true positives minus false positives (0-12). Recall task has 12 words and involves to recall of words after all of them are read aloud to the patient. Delayed recall tasks involves the same twelve words, except recall is tasked after a 20-25 minute delay. Recognition task has 24 words. Patient evaluated on how many from original list he or she is able to recognize. Higher scores = better outcomes. Retention scores appear in this entry below.

15. Change in Cognitive Status as Measured by the Hopkins Verbal Learning Test (HVLT) [Baseline and 12 weeks]

    Evaluates cognitive functioning across domains: recall, delayed recall, retention, recognition (each scored separately). The scores given are titled: recall score, delayed recall score, retention score, recognition discrimination index. Total Recall score = items correctly recalled (0-12). Delayed Recall score = items correctly recalled following delay (0-12). Retention score = percent items recalled that were also recalled after delay (0-100). The Recognition Discrimination score = true positives minus false positives (0-12). Recall task has 12 words and involves to recall of words after all of them are read aloud to the patient. Delayed recall tasks involves the same twelve words, except recall is tasked after a 20-25 minute delay. Recognition task has 24 words. Patient evaluated on how many from original list he or she is able to recognize. Higher scores = better outcomes. Recognition Discrimination Index appears in this entry below

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must have type I Bipolar disorder by DSM-IV criteria confirmed on the Mini Neuropsychiatric Interview (MINI)

• Subjects must be age 60 or older

• Subjects must have sub-optimal response to current psychotropic management including at least one of the following:

1. Behaviors and symptoms of irritability, agitation, mood lability or diminished ability to interact with others in their place of residence

2. Diminished ability to take care of basic personal needs in their place of residence due to symptoms of BD

Exclusion Criteria:

• History of intolerance or resistance to asenapine

• Clinical diagnosis of dementia or Mini-mental state (MMSE) < 24

• History of TIA, stroke or MI within the past 12 months

• Medical illness that is the clear, underlying etiology of BD

• Unstable medical illness or condition including prolonged QT interval, which in the opinion of the study investigators, is likely to affect the outcome of the study or the subject's safety

• DSM-IV substance dependence (except nicotine or caffeine) within the past 3 months.

• Rapid cycling BD defined as 4 or more discrete mood episodes within the previous 12 months.

• At high risk for self-harm or suicide

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106

Sponsors and Collaborators

• University Hospitals Cleveland Medical Center
• Case Western Reserve University

Investigators

• Principal Investigator: Martha Sajatovic, M.D., University Hospitals Cleveland Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Martha Sajatovic, Professor of Psychiatry, University Hospitals Cleveland Medical Center
• ClinicalTrials.gov Identifier: NCT01460290
• Other Study ID Numbers: 39358
• First Posted: Oct 26, 2011
• Last Update Posted: Dec 30, 2014
• Last Verified: Dec 1, 2014

• Additional relevant MeSH terms: Bipolar Disorder; Asenapine

Study Results

Participant Flow

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment. Asenapine was administered open-label in pill form. Asenapine was initiated at 5 mg and increased as tolerated to a maximum of 20 mg/day. A control group was not used for this study.
Period Title: Overall Study
STARTED	15
COMPLETED	11
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment Asenapine was administered open-label in pill form. Asenapine was initiated at 5 mg/day and increased as tolerated to a maximum of 20 mg/day. A control group was not used for this study.
Overall Participants	15
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.6 (6.1)
Sex: Female, Male (Count of Participants)
Female	8 53.3%
Male	7 46.7%

Outcome Measures

1. Primary Outcome

Title	Change in Depressive Symptoms as Measured by the Hamilton Depression Rating Scale (HAM-D)
Description	The minimum possible score is 0 and the maximum score is 52. A higher score implies a worse condition.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Participants with baseline HAM-D score of 8 or greater were analyzed. Last Observational Carried Forward (LOCF).

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment. Asenapine was administered open-label in pill form. Asenapine was initiated at 5 mg and increased as tolerated to a maximum of 20 mg/day. A control group was not used for this study.
Measure Participants	11
Baseline HAM-D	17.5 (4.8)
12 Week HAM-D	10.3 (6.3)

2. Primary Outcome

Title	Change in Manic Symptoms as Measured by the Young Mania Rating Scale (YMRS)
Description	The minimum possible score is 0 and the maximum score is 60. A higher score implies a worse condition.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Participants with a baseline YMRS score of 12 or greater were analyzed. LOCF

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment. Asenapine was administered open-label in pill form. Asenapine was initiated at 5 mg and increased as tolerated to a maximum of 20 mg/day. A control group was not used for this study.
Measure Participants	5
Baseline YMRS	27.9 (4.4)
12 Week YMRS	18.1 (14.2)

3. Secondary Outcome

Title	Change in Global Psychopathology as Measured by the Clinical Global Impression Scale for Use in Bipolar Illness (CGI-BP)
Description	The minimum possible score is 1 and the maximum score is 7. A higher score implies a worse condition. The CGI-BP has three scores - Mania Severity, Depression Severity, and Overall Bipolar Illness Severity.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Intention To Treat (ITT) and LOCF

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment. Asenapine was administered open-label in pill form. Asenapine was initiated at 5 mg and increased as tolerated to a maximum of 20 mg/day. A control group was not used for this study.
Measure Participants	15
Baseline Overall Severity	4.4 (1.0)
12 Week Overall Severity	2.2 (1.0)
Baseline Mania Severity	2.7 (1.7)
12 Week Mania Severity	1.9 (1.1)
Baseline Depression Severity	3.6 (1.5)
12 Week Depression Severity	1.7 (0.7)

4. Secondary Outcome

Title	Change in Perception of Physical Health as Measured by the Short Form General Health Survey (SF-12)
Description	The minimum possible score is 1 and the maximum score is 99. A higher score implies a better perceived condition.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

ITT and LOCF.

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment Asenapine: Asenapine will be administered open-label in pill form. Asenapine will be initiated at 5 mg twice a day and increased as tolerated to a maximum of 20 mg/day. It is anticipated that maximum stable dosing will be achieved by 4 weeks of treatment, although dosage may be reduced due to tolerability concerns at the discretion of the treating research psychiatrist.
Measure Participants	15
Baseline on Physical Health Subscale of SF-12	46.8 (11.3)
12 week on Physical Health Subscale of SF-12	46.4 (12.1)

5. Secondary Outcome

Title	Change in Perception of Mental Health as Measured by the Short Form General Health Survey (SF-12)
Description	The minimum possible score is 1 and the maximum score is 99. A higher score implies a better perceived condition.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

ITT and LOCF.

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment Asenapine: Asenapine will be administered open-label in pill form. Asenapine will be initiated at 5 mg twice a day and increased as tolerated to a maximum of 20 mg/day. It is anticipated that maximum stable dosing will be achieved by 4 weeks of treatment, although dosage may be reduced due to tolerability concerns at the discretion of the treating research psychiatrist.
Measure Participants	15
Baseline Mental Health Subscore of SF-12	38.7 (15.3)
12 Week Mental Health Subscore of SF-12	43.1 (13.1)

6. Secondary Outcome

Title	Change in Depressive Symptoms as Measured by the Montgomery Asberg Depression Rating Scale (MADRS)
Description	The minimum possible score is 0 and the maximum score is 60. A higher score implies a worse condition.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Participants with a baseline MADRS score of 16 or greater were analyzed. LOCF

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment Asenapine: Asenapine will be administered open-label in pill form. Asenapine will be initiated at 5 mg twice a day and increased as tolerated to a maximum of 20 mg/day. It is anticipated that maximum stable dosing will be achieved by 4 weeks of treatment, although dosage may be reduced due to tolerability concerns at the discretion of the treating research psychiatrist.
Measure Participants	9
Baseline MADRS	27.9 (4.4)
12 Week MADRS	18.1 (14.2)

7. Secondary Outcome

Title	Change in Bipolar Disorder Symptoms as Measured by the Brief Psychiatric Rating Scale (BPRS)
Description	The minimum possible score is 18 and the maximum score is 126. A higher score implies a worse condition.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

ITT and LOCF.

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment Asenapine: Asenapine will be administered open-label in pill form. Asenapine will be initiated at 5 mg twice a day and increased as tolerated to a maximum of 20 mg/day. It is anticipated that maximum stable dosing will be achieved by 4 weeks of treatment, although dosage may be reduced due to tolerability concerns at the discretion of the treating research psychiatrist.
Measure Participants	15
Baseline BPRS	35.1 (9.2)
12 Week BPRS	28.6 (9.4)

8. Secondary Outcome

Title	Change in Cognitive Status as Measured by the Stroop Task
Description	The Stroop evaluates patients for cognitive functioning. Patients are to read words aloud or name colors as quickly as possible in a 45-second period. The measure contains three tasks, each associated with a subscale as follows: Word, Color, and Color-Word. Each subscale contains 100 items. The raw score range for each of the subscales is 0-100. Each raw subscale score is converted to a T-Score. The possible T-Score range for the Word subscale is 15 to 85. The possible T-Score range for the Color subscale is 8 to 92. The possible T-Score range for the Color-Word subscale is 3 to 98. Higher scores on the subscales indicate better cognitive functioning. Subscales are scored independently and are not added to produce a total score.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Participants who completed cognitive scales at baseline and at Week 12 visit were analyzed.

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment Asenapine: Asenapine will be administered open-label in pill form. Asenapine will be initiated at 5 mg twice a day and increased as tolerated to a maximum of 20 mg/day. It is anticipated that maximum stable dosing will be achieved by 4 weeks of treatment, although dosage may be reduced due to tolerability concerns at the discretion of the treating research psychiatrist.
Measure Participants	9
Baseline Word Subscale	75.7 (12.0)
12 Week Word Subscale	75.9 (11.5)
Baseline Color Subscale	53.6 (9.2)
12 Week Color Subscale	58.6 (7.7)
Baseline Color-Word Subscale	30.3 (11.4)
12 Week Color-Word Subscale	30.6 (10.1)

9. Secondary Outcome

Title	Change in Cognitive Status as Measured by the Trail Making Test
Description	The Trails test is a measure of cognitive functioning. The measure consists of two parts: A and B. In part A, participants are asked to draw a trail connecting a series of numbers in sequential order. In Part B, participants are asked to draw a trail connecting a combination of letters and numbers. The time taken to complete each task is noted as the score (e.g., 78 seconds). For Trails A, there is no upper limit on the score, as subjects are given as much time as is needed for them to complete the task. Higher scores indicate poorer cognitive functioning. In Trails B, the task is timed with an upper limit of five minutes. If, at four minutes, it is determined that the subject will not likely complete the task in the time allotted, then the task can be called off. Higher scores indicate poorer cognitive functioning.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Participants who completed cognitive scales at baseline and at Week 12 visit were analyzed.

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment Asenapine: Asenapine will be administered open-label in pill form. Asenapine will be initiated at 5 mg twice a day and increased as tolerated to a maximum of 20 mg/day. It is anticipated that maximum stable dosing will be achieved by 4 weeks of treatment, although dosage may be reduced due to tolerability concerns at the discretion of the treating research psychiatrist.
Measure Participants	9
Baseline Trails - Part A	57.7 (30.9)
12 Week Trails - Part A	47.3 (10.4)
Baseline Trails - Part B	189.0 (103.8)
12 Week Trails - Part B	126.3 (52.4)

10. Secondary Outcome

Title	Change in Cognitive Status as Measured by the Hopkins Verbal Learning Test (HVLT)
Description	Evaluates cognitive functioning across domains: recall, delayed recall, retention, recognition (each scored separately). The scores given are titled: recall score, delayed recall score, retention score, recognition discrimination index. Total Recall score = items correctly recalled (0-36). Delayed Recall score = items correctly recalled following delay (0-12). Retention score = percent items recalled that were also recalled after delay (0-100). The Recognition Discrimination score = true positives minus false positives (0-12). Recall task has 12 words and involves to recall of words after all of them are read aloud to the patient. Delayed recall tasks involves the same twelve words, except recall is tasked after a 20-25 minute delay. Recognition task has 24 words. Patient evaluated on how many from original list he or she is able to recognize. Higher scores = better outcomes. Total recall scores appear in this entry below.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Participants who completed cognitive scales at baseline and at Week 12 visit were analyzed.

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment Asenapine: Asenapine will be administered open-label in pill form. Asenapine will be initiated at 5 mg twice a day and increased as tolerated to a maximum of 20 mg/day. It is anticipated that maximum stable dosing will be achieved by 4 weeks of treatment, although dosage may be reduced due to tolerability concerns at the discretion of the treating research psychiatrist.
Measure Participants	9
Baseline HVLT Total Recall	15.8 (5.7)
12 Week HVLT Total Recall	18.2 (5.4)

11. Secondary Outcome

Title	Change in Cognitive Status as Measured by the Dementia Rating Scale (DRS)
Description	The DRS contains items that evaluate cognitive function across 5 subscales: attention, initiation/perseveration, construction, conceptualization, and memory. Subscale raw score ranges are: attention (0-37), initiation/perseveration (0-37), construction (0-6), conceptualization (0-39), and memory (0-25). Raw subscale scores are added for a total raw score with range 0-144. For each raw subscale score, scaled scores are looked up from a battery of 13 tables. Age of the participant determines which table is to be used. Total raw subscale score also has its own scaled score in the tables. In addition to use in determining scaled scores for each of the subscales, these tables are used to look up the scaled score for the total raw score. The tables are contained in the article Robust and Expanded Norms for the Dementia Rating Scale (Pedraza, Lucas, et al. 2010); Archives of Clinical Neuropsychology 25; 347-358. Higher scores, raw and scaled, indicate better cognitive functioning.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Participants who completed cognitive scales at baseline and at Week 12 visit were analyzed.

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment Asenapine: Asenapine will be administered open-label in pill form. Asenapine will be initiated at 5 mg twice a day and increased as tolerated to a maximum of 20 mg/day. It is anticipated that maximum stable dosing will be achieved by 4 weeks of treatment, although dosage may be reduced due to tolerability concerns at the discretion of the treating research psychiatrist.
Measure Participants	9
Baseline DRS	131.2 (6.6)
12 Week DRS	135.6 (6.6)

12. Secondary Outcome

Title	World Health Organization Disability Assessment Scale (WHO-DAS)
Description	The WHO-DAS II is used to assess patients for difficulties that they experience due to health conditions. Six subscales are represented which cover the following domains: Getting Around (range 1-10), Self Care (range 1-10), Life Activities (range 1-20), Understand/Communicate (range 1-10), Participation in Society (range 1-10), and Getting Along with People (range 1-10). Lower scores represent more positive outcomes, while higher scores represent worse outcomes. Total summary scores were not computed for our analyses and is optional for the measure.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

ITT and LOCF.

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment Asenapine: Asenapine will be administered open-label in pill form. Asenapine will be initiated at 5 mg twice a day and increased as tolerated to a maximum of 20 mg/day. It is anticipated that maximum stable dosing will be achieved by 4 weeks of treatment, although dosage may be reduced due to tolerability concerns at the discretion of the treating research psychiatrist.
Measure Participants	15
Baseline WHO-DAS Getting Around Subscale	4.3 (2.7)
12 Week WHO-DAS Getting Around Subscale	4.7 (2.9)
Baseline WHO-DAS Self Care Subscale	2.6 (1.3)
12 Week WHO-DAS Self Care Subscale	2.4 (0.7)
Baseline WHO-DAS Life Activities Subscale	9.1 (4.9)
12 Week WHO-DAS Life Activities Subscale	7.1 (3.5)
Baseline WHO-DAS Understand/Communicate Subscale	3.6 (1.8)
12 Week WHO-DAS Understand/Communicate Subscale	3.1 (1.2)
Baseline WHO-DAS Participation in Society Subscale	4.3 (2.6)
12 Week WHO-DAS Participation in Society Subscale	3.8 (2.0)
Baseline WHO-DAS Getting Along w/ People Subscale	3.0 (1.5)
12 Week WHO-DAS Getting Along w/ People Subscale	2.9 (1.9)

13. Secondary Outcome

Title	Barnes Drug-induced Akathisia Rating Scale (BARS)
Description	This scale is used to measure the presence of akathisia, as may result from use of certain psychotropic medications. The scale contains four items and the score for each item is added to produce the total score. Total scores range from 0 to 14. Higher scores indicate more adverse outcomes.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

ITT and LOCF.

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment Asenapine: Asenapine will be administered open-label in pill form. Asenapine will be initiated at 5 mg twice a day and increased as tolerated to a maximum of 20 mg/day. It is anticipated that maximum stable dosing will be achieved by 4 weeks of treatment, although dosage may be reduced due to tolerability concerns at the discretion of the treating research psychiatrist.
Measure Participants	15
Baseline BARS	0.0 (0.0)
12 Week BARS	0.1 (0.5)

14. Secondary Outcome

Title	Assessment of Motor Control Abnormality as Measured by the Simpson Angus Scale (SAS)
Description	The Simpson-Angus Scale is used to monitor for neurological and musculoskeletal side effects that may be a result of certain psychotropic medications. The scale consists of 10 questions which each can be rated on a scale of 0 to 4. Scores for each item are added to produce a total score. The highest possible total score is 40. Higher scores indicate more adverse outcomes.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

ITT and LOCF.

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment Asenapine: Asenapine will be administered open-label in pill form. Asenapine will be initiated at 5 mg twice a day and increased as tolerated to a maximum of 20 mg/day. It is anticipated that maximum stable dosing will be achieved by 4 weeks of treatment, although dosage may be reduced due to tolerability concerns at the discretion of the treating research psychiatrist.
Measure Participants	15
Baseline SAS	0.4 (0.8)
12 Week SAS	0.5 (0.7)

15. Secondary Outcome

Title	Change in Cognitive Status as Measured by the Hopkins Verbal Learning Test (HVLT)
Description	Evaluates cognitive functioning across domains: recall, delayed recall, retention, recognition (each scored separately). The scores given are titled: recall score, delayed recall score, retention score, recognition discrimination index. Total Recall score = items correctly recalled (0-12). Delayed Recall score = items correctly recalled following delay (0-12). Retention score = percent items recalled that were also recalled after delay (0-100). The Recognition Discrimination score = true positives minus false positives (0-12). Recall task has 12 words and involves to recall of words after all of them are read aloud to the patient. Delayed recall tasks involves the same twelve words, except recall is tasked after a 20-25 minute delay. Recognition task has 24 words. Patient evaluated on how many from original list he or she is able to recognize. Higher scores = better outcomes. Delayed recall scores appear in this entry below.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Participants who completed cognitive scales at baseline and at Week 12 visit were analyzed.

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment Asenapine: Asenapine will be administered open-label in pill form. Asenapine will be initiated at 5 mg twice a day and increased as tolerated to a maximum of 20 mg/day. It is anticipated that maximum stable dosing will be achieved by 4 weeks of treatment, although dosage may be reduced due to tolerability concerns at the discretion of the treating research psychiatrist.
Measure Participants	9
Baseline HVLT Delayed Recall	5.2 (3.0)
12 Week HVLT Delayed Recall	5.3 (2.7)

16. Secondary Outcome

Title	Change in Cognitive Status as Measured by the Hopkins Verbal Learning Test (HVLT)
Description	Evaluates cognitive functioning across domains: recall, delayed recall, retention, recognition (each scored separately). The scores given are titled: recall score, delayed recall score, retention score, recognition discrimination index. Total Recall score = items correctly recalled (0-12). Delayed Recall score = items correctly recalled following delay (0-12). Retention score = percent items recalled that were also recalled after delay (0-100). The Recognition Discrimination score = true positives minus false positives (0-12). Recall task has 12 words and involves to recall of words after all of them are read aloud to the patient. Delayed recall tasks involves the same twelve words, except recall is tasked after a 20-25 minute delay. Recognition task has 24 words. Patient evaluated on how many from original list he or she is able to recognize. Higher scores = better outcomes. Retention scores appear in this entry below.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Participants who completed cognitive scales at baseline and at Week 12 visit were analyzed.

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment Asenapine: Asenapine will be administered open-label in pill form. Asenapine will be initiated at 5 mg twice a day and increased as tolerated to a maximum of 20 mg/day. It is anticipated that maximum stable dosing will be achieved by 4 weeks of treatment, although dosage may be reduced due to tolerability concerns at the discretion of the treating research psychiatrist.
Measure Participants	9
Baseline HVLT Retention	73.9 (32.7)
12 Week HVLT Retention	71.8 (34.4)

17. Secondary Outcome

Title	Change in Cognitive Status as Measured by the Hopkins Verbal Learning Test (HVLT)
Description	Evaluates cognitive functioning across domains: recall, delayed recall, retention, recognition (each scored separately). The scores given are titled: recall score, delayed recall score, retention score, recognition discrimination index. Total Recall score = items correctly recalled (0-12). Delayed Recall score = items correctly recalled following delay (0-12). Retention score = percent items recalled that were also recalled after delay (0-100). The Recognition Discrimination score = true positives minus false positives (0-12). Recall task has 12 words and involves to recall of words after all of them are read aloud to the patient. Delayed recall tasks involves the same twelve words, except recall is tasked after a 20-25 minute delay. Recognition task has 24 words. Patient evaluated on how many from original list he or she is able to recognize. Higher scores = better outcomes. Recognition Discrimination Index appears in this entry below
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Participants who completed cognitive scales at baseline and at Week 12 visit were analyzed.

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment Asenapine: Asenapine will be administered open-label in pill form. Asenapine will be initiated at 5 mg twice a day and increased as tolerated to a maximum of 20 mg/day. It is anticipated that maximum stable dosing will be achieved by 4 weeks of treatment, although dosage may be reduced due to tolerability concerns at the discretion of the treating research psychiatrist.
Measure Participants	9
Baseline HVLT Recognition Discrimation Index	8.6 (2.5)
12 Week HVLT Recognition Discrimination Index	9.6 (2.0)

Adverse Events

Arm/Group Title	Asenapine
Arm/Group Description	12-weeks of open-label asenapine treatment Asenapine: Asenapine will be administered open-label in pill form. Asenapine will be initiated at 5 mg twice a day and increased as tolerated to a maximum of 20 mg/day. It is anticipated that maximum stable dosing will be achieved by 4 weeks of treatment, although dosage may be reduced due to tolerability concerns at the discretion of the treating research psychiatrist.
All Cause Mortality
	Asenapine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Asenapine
	Affected / at Risk (%)	# Events
Total	3/15 (20%)
Psychiatric disorders
emergence of manic symptoms	1/15 (6.7%)	1
recurrence of suicidal ideation	1/15 (6.7%)	1
reported dizziness/refusal to take additional mood stabilizer	1/15 (6.7%)	1
Other (Not Including Serious) Adverse Events
	Asenapine
	Affected / at Risk (%)	# Events
Total	13/15 (86.7%)
Gastrointestinal disorders
gastrointestinal discomfort	5/15 (33.3%)	5
General disorders
restlessness	2/15 (13.3%)	2
tremors	2/15 (13.3%)	2
cognitive difficulties	2/15 (13.3%)	2
sluggishness/sedation	2/15 (13.3%)	2
Hepatobiliary disorders
elevated liver functions	1/15 (6.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.