Trial Outcomes & Findings for Antipsychotic Discontinuation in Alzheimer's Disease (NCT NCT00417482)
NCT ID: NCT00417482
Last Updated: 2013-04-24
Results Overview
A relapse occurred in Phase B (post-randomization) if both of the following criteria were met: 1. Increase in the Neuropsychiatric Inventory (NPI) core score of 30% or more OR a 5-point increase from the baseline NPI score at the end of Phase A 2. A score of 6 (much worse) or 7 (very much worse) on the Clinical Global Impression-Change (CGI-C) at any visit.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
180 participants
Primary outcome timeframe
0-16 weeks in Phase B (16-32 weeks in study)
Results posted on
2013-04-24
Participant Flow
Patients were recruited from memory clinics including Alzheimer Research Centers, geriatric psychiatry clinics, VA clinics, physician referrals and advertising.
180 Patients with Alzheimer's disease (AD) \& psychosis or agitation-aggression received open treatment with risperidone for 16 weeks in Phase A. Of 180 patients, 112 were responders and 110 were randomized in Phase B. Phase B: 110 responders were randomized, double-blind, to one of three arms in Phase B.
Participant milestones
| Measure |
Arm 1: Risperidone-Risperidone
Phase A involved open flexible dose risperidone treatment for 16 weeks. At 16 weeks, non-responders exited the study. Responders were randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for 32 weeks (Arm 1), (2) risperidone for 16 weeks followed by placebo for 16 weeks (Arm 2), (3) placebo for 32 weeks (Arm 3).
Phase B Arm 1: Risperidone for 16 weeks followed by risperidone for 16 weeks; Risperidone open label flexible dose was administered at a dose of 0.25 to 3 mg daily for first 16 weeks; dose at 16 weeks then fixed for the randomized trial
|
Phase B Arm 2: Risperidone-Placebo
Phase A involved open flexible dose risperidone treatment for 16 weeks. At 16 weeks, non-responders exited the study. Responders were randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for 32 weeks (Arm 1), (2) risperidone for 16 weeks followed by placebo for 16 weeks (Arm 2), (3) placebo for 32 weeks (Arm 3).
Phase B Arm 2: Risperidone for 16 weeks followed by placebo for 16 weeks;
|
Phase B Arm 3: Placebo-Placebo
Phase A involved open flexible dose risperidone treatment for 16 weeks. At 16 weeks, non-responders exited the study. Responders were randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for 32 weeks (Arm 1), (2) risperidone for 16 weeks followed by placebo for 16 weeks (Arm 2), (3) placebo for 32 weeks (Arm 3).
Phase B Arm 3: Patients were randomized to placebo for 32 weeks.
|
|---|---|---|---|
|
Phase B 1st 16 Weeks
STARTED
|
32
|
38
|
40
|
|
Phase B 1st 16 Weeks
COMPLETED
|
13
|
27
|
13
|
|
Phase B 1st 16 Weeks
NOT COMPLETED
|
19
|
11
|
27
|
|
Phase B 2nd 16 Weeks
STARTED
|
13
|
27
|
13
|
|
Phase B 2nd 16 Weeks
COMPLETED
|
10
|
14
|
10
|
|
Phase B 2nd 16 Weeks
NOT COMPLETED
|
3
|
13
|
3
|
Reasons for withdrawal
| Measure |
Arm 1: Risperidone-Risperidone
Phase A involved open flexible dose risperidone treatment for 16 weeks. At 16 weeks, non-responders exited the study. Responders were randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for 32 weeks (Arm 1), (2) risperidone for 16 weeks followed by placebo for 16 weeks (Arm 2), (3) placebo for 32 weeks (Arm 3).
Phase B Arm 1: Risperidone for 16 weeks followed by risperidone for 16 weeks; Risperidone open label flexible dose was administered at a dose of 0.25 to 3 mg daily for first 16 weeks; dose at 16 weeks then fixed for the randomized trial
|
Phase B Arm 2: Risperidone-Placebo
Phase A involved open flexible dose risperidone treatment for 16 weeks. At 16 weeks, non-responders exited the study. Responders were randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for 32 weeks (Arm 1), (2) risperidone for 16 weeks followed by placebo for 16 weeks (Arm 2), (3) placebo for 32 weeks (Arm 3).
Phase B Arm 2: Risperidone for 16 weeks followed by placebo for 16 weeks;
|
Phase B Arm 3: Placebo-Placebo
Phase A involved open flexible dose risperidone treatment for 16 weeks. At 16 weeks, non-responders exited the study. Responders were randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for 32 weeks (Arm 1), (2) risperidone for 16 weeks followed by placebo for 16 weeks (Arm 2), (3) placebo for 32 weeks (Arm 3).
Phase B Arm 3: Patients were randomized to placebo for 32 weeks.
|
|---|---|---|---|
|
Phase B 1st 16 Weeks
Lack of Efficacy
|
14
|
8
|
24
|
|
Phase B 1st 16 Weeks
Adverse Event
|
2
|
0
|
1
|
|
Phase B 1st 16 Weeks
Moved, Unclear reasons
|
2
|
3
|
2
|
|
Phase B 1st 16 Weeks
Death
|
1
|
0
|
0
|
|
Phase B 2nd 16 Weeks
Lack of Efficacy
|
1
|
12
|
2
|
|
Phase B 2nd 16 Weeks
Adverse Event
|
0
|
0
|
1
|
|
Phase B 2nd 16 Weeks
Moved; unclear reason
|
1
|
0
|
0
|
|
Phase B 2nd 16 Weeks
Death
|
1
|
1
|
0
|
Baseline Characteristics
Antipsychotic Discontinuation in Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
Phase B Arm 1: Risperidone-Risperidone
n=32 Participants
Phase A involved open flexible dose risperidone treatment for 16 weeks. At 16 weeks, non-responders exited the study. Responders were randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for 32 weeks (Arm 1), (2) risperidone for 16 weeks followed by placebo for 16 weeks (Arm 2), (3) placebo for 32 weeks (Arm 3). For patients receiving risperidone ≥ 2 mg daily at end-Phase A, assignment to placebo in Phase B required an initial one-week taper with sequential double-blind placebo substitution (e.g., one 2 mg tablet switched to one 1 mg tablet and then to one placebo tablet) to reduce antipsychotic physical withdrawal effects.
|
Phase B Arm 2: Risperidone -Placebo
n=38 Participants
Phase A involved open flexible dose risperidone treatment for 16 weeks. At 16 weeks, non-responders exited the study. Responders were randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for 32 weeks (Arm 1), (2) risperidone for 16 weeks followed by placebo for 16 weeks (Arm 2), (3) placebo for 32 weeks (Arm 3). For patients receiving risperidone ≥ 2 mg daily at end-Phase A, assignment to placebo in Phase B required an initial one-week taper with sequential double-blind placebo substitution (e.g., one 2 mg tablet switched to one 1 mg tablet and then to one placebo tablet) to reduce antipsychotic physical withdrawal effects.
|
Phase B Arm 3: Placebo-Placebo
n=40 Participants
Phase A involved open flexible dose risperidone treatment for 16 weeks. At 16 weeks, non-responders exited the study. Responders were randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for 32 weeks (Arm 1), (2) risperidone for 16 weeks followed by placebo for 16 weeks (Arm 2), (3) placebo for 32 weeks (Arm 3). For patients receiving risperidone ≥ 2 mg daily at end-Phase A, assignment to placebo in Phase B required an initial one-week taper with sequential double-blind placebo substitution (e.g., one 2 mg tablet switched to one 1 mg tablet and then to one placebo tablet) to reduce antipsychotic physical withdrawal effects.
|
Total
n=110 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
30 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
103 Participants
n=4 Participants
|
|
Age Continuous
|
80.7 years
STANDARD_DEVIATION 7.9 • n=5 Participants
|
79.1 years
STANDARD_DEVIATION 8.0 • n=7 Participants
|
80.3 years
STANDARD_DEVIATION 7.7 • n=5 Participants
|
80.0 years
STANDARD_DEVIATION 7.8 • n=4 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
66 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
44 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
32 participants
n=5 Participants
|
38 participants
n=7 Participants
|
40 participants
n=5 Participants
|
110 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 0-16 weeks in Phase B (16-32 weeks in study)Population: Analysis was performed as per intention to treat (ITT) principles.
A relapse occurred in Phase B (post-randomization) if both of the following criteria were met: 1. Increase in the Neuropsychiatric Inventory (NPI) core score of 30% or more OR a 5-point increase from the baseline NPI score at the end of Phase A 2. A score of 6 (much worse) or 7 (very much worse) on the Clinical Global Impression-Change (CGI-C) at any visit.
Outcome measures
| Measure |
Phase B Arm 1: Risperidone-Risperidone
n=32 Participants
32 patients randomized to Phase B Arm 1 received continuation risperidone for another 32 weeks.
|
Phase B Arm 2: Risperidone -Placebo
n=38 Participants
38 patients randomized to Phase B Arm 2 received risperidone therapy for 16 weeks followed by placebo for 16 weeks.
In Phase B, relapse required ≥ 30% increase or 5-point increase in NPI core scores from end-Phase A and a score of 6 (much worse) or 7 (very much worse) on the CGI-C.
|
Phase B Arm 3: Placebo-Placebo
n=40 Participants
40 patients randomized to Phase B Arm 3 received placebo for 32 weeks. For patients receiving risperidone ≥ 2 mg daily at end-Phase A, assignment to placebo in Phase B required an initial one-week taper with sequential double-blind placebo substitution (e.g., one 2 mg tablet switched to one 1 mg tablet and then to one placebo tablet) to reduce antipsychotic physical withdrawal effects.
In Phase B, relapse required ≥ 30% increase or 5-point increase in NPI core scores from end-Phase A and a score of 6 (much worse) or 7 (very much worse) on the CGI-C.
|
|---|---|---|---|
|
Relapse by Study Week 32
|
15 participants
|
8 participants
|
24 participants
|
SECONDARY outcome
Timeframe: 16-32 weeks in Phase B (32-48 weeks in study)Population: Randomized subjects in each Arm who had not relapsed or terminated the study by the end of the first 16 weeks of Phase B were analyzed in the second 16 weeks of Phase B using intent to treat (ITT) principles.
Same definition and criteria as the primary outcome
Outcome measures
| Measure |
Phase B Arm 1: Risperidone-Risperidone
n=13 Participants
32 patients randomized to Phase B Arm 1 received continuation risperidone for another 32 weeks.
|
Phase B Arm 2: Risperidone -Placebo
n=27 Participants
38 patients randomized to Phase B Arm 2 received risperidone therapy for 16 weeks followed by placebo for 16 weeks.
In Phase B, relapse required ≥ 30% increase or 5-point increase in NPI core scores from end-Phase A and a score of 6 (much worse) or 7 (very much worse) on the CGI-C.
|
Phase B Arm 3: Placebo-Placebo
40 patients randomized to Phase B Arm 3 received placebo for 32 weeks. For patients receiving risperidone ≥ 2 mg daily at end-Phase A, assignment to placebo in Phase B required an initial one-week taper with sequential double-blind placebo substitution (e.g., one 2 mg tablet switched to one 1 mg tablet and then to one placebo tablet) to reduce antipsychotic physical withdrawal effects.
In Phase B, relapse required ≥ 30% increase or 5-point increase in NPI core scores from end-Phase A and a score of 6 (much worse) or 7 (very much worse) on the CGI-C.
|
|---|---|---|---|
|
Relapse by Study Week 48
|
2 participants
|
13 participants
|
—
|
SECONDARY outcome
Timeframe: Phase B, weeks 1-16 (study weeks 16-32)Population: MMSE data were missing for 2 subjects in the placebo group and 1 subject in the risperidone group, so the number of subjects in this analysis were 38 (placebo) and 69 (risperidone), for a total of 107.
The MMSE assesses cognition. Scores range from 0-30, with higher scores indicating better cognition. For each subject, the change in MMSE between week 16 and baseline (randomization) was calculated by subtraction, so that a positive value indicates an increase in MMSE over time.
Outcome measures
| Measure |
Phase B Arm 1: Risperidone-Risperidone
n=38 Participants
32 patients randomized to Phase B Arm 1 received continuation risperidone for another 32 weeks.
|
Phase B Arm 2: Risperidone -Placebo
n=69 Participants
38 patients randomized to Phase B Arm 2 received risperidone therapy for 16 weeks followed by placebo for 16 weeks.
In Phase B, relapse required ≥ 30% increase or 5-point increase in NPI core scores from end-Phase A and a score of 6 (much worse) or 7 (very much worse) on the CGI-C.
|
Phase B Arm 3: Placebo-Placebo
40 patients randomized to Phase B Arm 3 received placebo for 32 weeks. For patients receiving risperidone ≥ 2 mg daily at end-Phase A, assignment to placebo in Phase B required an initial one-week taper with sequential double-blind placebo substitution (e.g., one 2 mg tablet switched to one 1 mg tablet and then to one placebo tablet) to reduce antipsychotic physical withdrawal effects.
In Phase B, relapse required ≥ 30% increase or 5-point increase in NPI core scores from end-Phase A and a score of 6 (much worse) or 7 (very much worse) on the CGI-C.
|
|---|---|---|---|
|
Mini Mental State Exam (MMSE)
|
-0.13 units on a scale
Standard Deviation 1.49
|
-0.77 units on a scale
Standard Deviation 2.23
|
—
|
SECONDARY outcome
Timeframe: Phase B, weeks 1-16 (study weeks 16-32)Population: All randomized subjects were included in this analysis (N=110)
The Treatment Emergent Symptom Scale (TESS) assesses 26 somatic symptoms. Total scores range from 0-26, with a score of 0 or 1 for each item. Higher scores indicate more somatic symptoms. For each subject, the change in TESS between week 16 and baseline (randomization) was calculated by subtraction, so that a positive value indicates an increase in TESS over time.
Outcome measures
| Measure |
Phase B Arm 1: Risperidone-Risperidone
n=40 Participants
32 patients randomized to Phase B Arm 1 received continuation risperidone for another 32 weeks.
|
Phase B Arm 2: Risperidone -Placebo
n=70 Participants
38 patients randomized to Phase B Arm 2 received risperidone therapy for 16 weeks followed by placebo for 16 weeks.
In Phase B, relapse required ≥ 30% increase or 5-point increase in NPI core scores from end-Phase A and a score of 6 (much worse) or 7 (very much worse) on the CGI-C.
|
Phase B Arm 3: Placebo-Placebo
40 patients randomized to Phase B Arm 3 received placebo for 32 weeks. For patients receiving risperidone ≥ 2 mg daily at end-Phase A, assignment to placebo in Phase B required an initial one-week taper with sequential double-blind placebo substitution (e.g., one 2 mg tablet switched to one 1 mg tablet and then to one placebo tablet) to reduce antipsychotic physical withdrawal effects.
In Phase B, relapse required ≥ 30% increase or 5-point increase in NPI core scores from end-Phase A and a score of 6 (much worse) or 7 (very much worse) on the CGI-C.
|
|---|---|---|---|
|
Treatment Emergent Symptoms Scale (TESS)
|
0.18 units on a scale
Standard Deviation 2.4
|
0.21 units on a scale
Standard Deviation 2.5
|
—
|
SECONDARY outcome
Timeframe: Phase B, weeks 1-16 (study weeks 16-32)Population: All randomized subjects were included in the analysis (N=110).
Extrapyramidal signs, also known as Parkinsonian signs, refer to signs of tremor, rigidity, and bradykinesia (slowed movement) that are seen in Parkinson's disease. Assessment of extrapyramidal signs (EPS) were made with the use of the Simpson-Angus scale (which ranges from 1-40) with higher scores indicating more extrapyramidal signs. For each subject, the change in EPS between week 16 and baseline (randomization) was calculated by subtraction, so that a positive value indicates an increase in EPS over time.
Outcome measures
| Measure |
Phase B Arm 1: Risperidone-Risperidone
n=40 Participants
32 patients randomized to Phase B Arm 1 received continuation risperidone for another 32 weeks.
|
Phase B Arm 2: Risperidone -Placebo
n=70 Participants
38 patients randomized to Phase B Arm 2 received risperidone therapy for 16 weeks followed by placebo for 16 weeks.
In Phase B, relapse required ≥ 30% increase or 5-point increase in NPI core scores from end-Phase A and a score of 6 (much worse) or 7 (very much worse) on the CGI-C.
|
Phase B Arm 3: Placebo-Placebo
40 patients randomized to Phase B Arm 3 received placebo for 32 weeks. For patients receiving risperidone ≥ 2 mg daily at end-Phase A, assignment to placebo in Phase B required an initial one-week taper with sequential double-blind placebo substitution (e.g., one 2 mg tablet switched to one 1 mg tablet and then to one placebo tablet) to reduce antipsychotic physical withdrawal effects.
In Phase B, relapse required ≥ 30% increase or 5-point increase in NPI core scores from end-Phase A and a score of 6 (much worse) or 7 (very much worse) on the CGI-C.
|
|---|---|---|---|
|
Extrapyramidal Signs (EPS)
|
-0.20 units on a scale
Standard Deviation 1.91
|
0.34 units on a scale
Standard Deviation 2.68
|
—
|
SECONDARY outcome
Timeframe: Phase B, weeks 1-16 (study weeks 16-32)Population: All randomized subjects were included in this analysis (N=110).
The Abnormal Involuntary Movement Scale (AIMS) assesses signs of tardive dyskinesia, a movement disorder that can occur with prolonged use of antipsychotic medication. The AIMS score ranges from 0 to 35, with higher scores indicating more severe symptoms. For each subject, the change in AIMS score between week 16 and randomization was calculated by subtraction, so that a positive value indicates an increase in AIMS over time.
Outcome measures
| Measure |
Phase B Arm 1: Risperidone-Risperidone
n=40 Participants
32 patients randomized to Phase B Arm 1 received continuation risperidone for another 32 weeks.
|
Phase B Arm 2: Risperidone -Placebo
n=70 Participants
38 patients randomized to Phase B Arm 2 received risperidone therapy for 16 weeks followed by placebo for 16 weeks.
In Phase B, relapse required ≥ 30% increase or 5-point increase in NPI core scores from end-Phase A and a score of 6 (much worse) or 7 (very much worse) on the CGI-C.
|
Phase B Arm 3: Placebo-Placebo
40 patients randomized to Phase B Arm 3 received placebo for 32 weeks. For patients receiving risperidone ≥ 2 mg daily at end-Phase A, assignment to placebo in Phase B required an initial one-week taper with sequential double-blind placebo substitution (e.g., one 2 mg tablet switched to one 1 mg tablet and then to one placebo tablet) to reduce antipsychotic physical withdrawal effects.
In Phase B, relapse required ≥ 30% increase or 5-point increase in NPI core scores from end-Phase A and a score of 6 (much worse) or 7 (very much worse) on the CGI-C.
|
|---|---|---|---|
|
AIMS
|
0.03 units on a scale
Standard Deviation 0.48
|
0.24 units on a scale
Standard Deviation 1.01
|
—
|
SECONDARY outcome
Timeframe: Phase B, weeks 1-16 (study weeks 16-32)Population: All randomized subjects were included in this analysis, with the exception of one placebo subject for whom PSMS data was not available at one time point
Physical Self-Maintenance Scale, which ranges from 1 to 30, with higher scores indicating WORSE functioning. For each subject, the change in PSMS between week 16 and randomization was calculated by subtraction, so that a positive value indicates an increase in PSMS (worse functioning) over time.
Outcome measures
| Measure |
Phase B Arm 1: Risperidone-Risperidone
n=39 Participants
32 patients randomized to Phase B Arm 1 received continuation risperidone for another 32 weeks.
|
Phase B Arm 2: Risperidone -Placebo
n=70 Participants
38 patients randomized to Phase B Arm 2 received risperidone therapy for 16 weeks followed by placebo for 16 weeks.
In Phase B, relapse required ≥ 30% increase or 5-point increase in NPI core scores from end-Phase A and a score of 6 (much worse) or 7 (very much worse) on the CGI-C.
|
Phase B Arm 3: Placebo-Placebo
40 patients randomized to Phase B Arm 3 received placebo for 32 weeks. For patients receiving risperidone ≥ 2 mg daily at end-Phase A, assignment to placebo in Phase B required an initial one-week taper with sequential double-blind placebo substitution (e.g., one 2 mg tablet switched to one 1 mg tablet and then to one placebo tablet) to reduce antipsychotic physical withdrawal effects.
In Phase B, relapse required ≥ 30% increase or 5-point increase in NPI core scores from end-Phase A and a score of 6 (much worse) or 7 (very much worse) on the CGI-C.
|
|---|---|---|---|
|
Physical Self-Maintenance Scale (PSMS)
|
0.18 units on a scale
Standard Deviation 1.73
|
0.80 units on a scale
Standard Deviation 2.72
|
—
|
SECONDARY outcome
Timeframe: Phase B, weeks 1-16 (study weeks 16-32)Population: Available data from all randomized subject (N=110) was used in this analysis. Weight measurements were unavailable at one or more time points for 3 subjects in the placebo group and for 6 subjects in the risperidone group.
For each subject, the change in weight in pounds between week 16 and randomization was calculated by subtraction, so that a positive value indicates an increase in weight over time.
Outcome measures
| Measure |
Phase B Arm 1: Risperidone-Risperidone
n=37 Participants
32 patients randomized to Phase B Arm 1 received continuation risperidone for another 32 weeks.
|
Phase B Arm 2: Risperidone -Placebo
n=64 Participants
38 patients randomized to Phase B Arm 2 received risperidone therapy for 16 weeks followed by placebo for 16 weeks.
In Phase B, relapse required ≥ 30% increase or 5-point increase in NPI core scores from end-Phase A and a score of 6 (much worse) or 7 (very much worse) on the CGI-C.
|
Phase B Arm 3: Placebo-Placebo
40 patients randomized to Phase B Arm 3 received placebo for 32 weeks. For patients receiving risperidone ≥ 2 mg daily at end-Phase A, assignment to placebo in Phase B required an initial one-week taper with sequential double-blind placebo substitution (e.g., one 2 mg tablet switched to one 1 mg tablet and then to one placebo tablet) to reduce antipsychotic physical withdrawal effects.
In Phase B, relapse required ≥ 30% increase or 5-point increase in NPI core scores from end-Phase A and a score of 6 (much worse) or 7 (very much worse) on the CGI-C.
|
|---|---|---|---|
|
Weight
|
0.32 pounds
Standard Deviation 7.18
|
0.73 pounds
Standard Deviation 8.71
|
—
|
Adverse Events
Wk0-16 Phase B Arm 1 (Risp-Risp) & Arm 2 (Risp-Pla)
Serious events: 5 serious events
Other events: 36 other events
Deaths: 0 deaths
Wk 0-16 Phase B Arm 3: Placebo -Placebo
Serious events: 8 serious events
Other events: 24 other events
Deaths: 0 deaths
Wk 17-32 Phase B Arm 1: Risperdone-Risperdone
Serious events: 2 serious events
Other events: 9 other events
Deaths: 0 deaths
Wk 17-32 Phase B Arm 2: Risperdone-Placebo
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Wek 17-32 Phase B Arm 3: Placebo -Placebo
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Wk0-16 Phase B Arm 1 (Risp-Risp) & Arm 2 (Risp-Pla)
n=70 participants at risk
32 patients randomized to Phase B Arm 1 received continuation risperidone for another 32 weeks; 38 patients randomized to Phase B Arm 2 received risperidone for 16 weeks followed by placebo for 16 weeks. Therefore there were a total of 70 patients in this group.
|
Wk 0-16 Phase B Arm 3: Placebo -Placebo
n=40 participants at risk
40 patients randomized to Phase B Arm 3 received placebo for 32 weeks.
|
Wk 17-32 Phase B Arm 1: Risperdone-Risperdone
n=13 participants at risk
13 patients completed Wk 0-16 of Phase 2 Arm 1 and entered Wk 17-32 where they received risperidone for another 16 weeks.
|
Wk 17-32 Phase B Arm 2: Risperdone-Placebo
n=27 participants at risk
27 patients completed Wk 0-16 of Phase B Arm 2 and entered Week 17-32 of Phase B Arm 2 where they receive placebo for 16 weeks.
|
Wek 17-32 Phase B Arm 3: Placebo -Placebo
n=13 participants at risk
13 patients completed Week 0-16 of Phase B Arm 3 and entered Week 17-32 were they were given placebo for another 16 weeks.
|
|---|---|---|---|---|---|
|
Cardiac disorders
Death
|
1.4%
1/70 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
2.5%
1/40 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
7.7%
1/13 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/27 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/13 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
|
Cardiac disorders
Cardiovascular Event
|
1.4%
1/70 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
2.5%
1/40 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
7.7%
1/13 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/27 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/13 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
|
Nervous system disorders
Neurologic Event
|
0.00%
0/70 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
2.5%
1/40 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/13 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/27 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/13 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
|
Psychiatric disorders
Agitation-Aggression
|
0.00%
0/70 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
5.0%
2/40 • Number of events 2 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/13 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/27 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/13 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Event
|
1.4%
1/70 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
2.5%
1/40 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/13 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/27 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/13 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
|
Musculoskeletal and connective tissue disorders
Fall or Fracture
|
4.3%
3/70 • Number of events 3 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/40 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/13 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/27 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/13 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
|
General disorders
Other
|
2.9%
2/70 • Number of events 2 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
5.0%
2/40 • Number of events 2 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/13 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/27 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/13 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
Other adverse events
| Measure |
Wk0-16 Phase B Arm 1 (Risp-Risp) & Arm 2 (Risp-Pla)
n=70 participants at risk
32 patients randomized to Phase B Arm 1 received continuation risperidone for another 32 weeks; 38 patients randomized to Phase B Arm 2 received risperidone for 16 weeks followed by placebo for 16 weeks. Therefore there were a total of 70 patients in this group.
|
Wk 0-16 Phase B Arm 3: Placebo -Placebo
n=40 participants at risk
40 patients randomized to Phase B Arm 3 received placebo for 32 weeks.
|
Wk 17-32 Phase B Arm 1: Risperdone-Risperdone
n=13 participants at risk
13 patients completed Wk 0-16 of Phase 2 Arm 1 and entered Wk 17-32 where they received risperidone for another 16 weeks.
|
Wk 17-32 Phase B Arm 2: Risperdone-Placebo
n=27 participants at risk
27 patients completed Wk 0-16 of Phase B Arm 2 and entered Week 17-32 of Phase B Arm 2 where they receive placebo for 16 weeks.
|
Wek 17-32 Phase B Arm 3: Placebo -Placebo
n=13 participants at risk
13 patients completed Week 0-16 of Phase B Arm 3 and entered Week 17-32 were they were given placebo for another 16 weeks.
|
|---|---|---|---|---|---|
|
Nervous system disorders
Extrapyramidal signs
|
18.6%
13/70 • Number of events 13 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
10.0%
4/40 • Number of events 4 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
30.8%
4/13 • Number of events 4 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
14.8%
4/27 • Number of events 4 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
15.4%
2/13 • Number of events 2 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
|
Nervous system disorders
akathisia or restlessness
|
5.7%
4/70 • Number of events 4 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
15.0%
6/40 • Number of events 6 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
7.7%
1/13 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
11.1%
3/27 • Number of events 3 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
7.7%
1/13 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
|
Nervous system disorders
sedation
|
10.0%
7/70 • Number of events 7 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
12.5%
5/40 • Number of events 5 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
7.7%
1/13 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
3.7%
1/27 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
7.7%
1/13 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
|
Nervous system disorders
insomnia
|
4.3%
3/70 • Number of events 3 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
2.5%
1/40 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/13 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
3.7%
1/27 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/13 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
|
Nervous system disorders
confusion
|
5.7%
4/70 • Number of events 4 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
10.0%
4/40 • Number of events 4 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
7.7%
1/13 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
11.1%
3/27 • Number of events 3 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
7.7%
1/13 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
|
Nervous system disorders
Agitation-Aggression
|
1.4%
1/70 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
2.5%
1/40 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/13 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
3.7%
1/27 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
7.7%
1/13 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
|
Nervous system disorders
fall
|
2.9%
2/70 • Number of events 2 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
2.5%
1/40 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/13 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/27 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/13 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
|
Gastrointestinal disorders
nausea or vomiting
|
2.9%
2/70 • Number of events 2 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
5.0%
2/40 • Number of events 2 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
15.4%
2/13 • Number of events 2 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
0.00%
0/27 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
7.7%
1/13 • Number of events 1 • Adverse event data were collected for the duration of the trial, in both the open treatment Phase A (study week 1-16) and in the post-randomization Phase B (study weeks 16-48)
|
Additional Information
Davangere P. Devanand, MD
New York State Psychiatric Institute
Phone: 212-543-5612
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place