Trial Outcomes & Findings for A Study of the Safety and Efficacy of Injectable Risperidone in the Prevention of Bipolar Mood Episodes (NCT NCT00132678)
NCT ID: NCT00132678
Last Updated: 2013-07-29
Results Overview
Mood Relapse was defined as: The subject met DSM-IV criteria for a manic, hypomanic, mixed, or depressive episode; or, the subject needed treatment intervention with any mood stabilizer, antipsychotic medication (other than study drug), benzodiazepine (beyond the dosage allowed), or antidepressant medication; or the subject required hospitalization for any bipolar mood episode; or the subject had a YMRS or MADRS score \>12 or a CGI-S score \>4; or a dose increase, or supplementation with oral risperidone or another antipsychotic or mood stabilizer, was needed in the opinion of the investigator.
COMPLETED
PHASE3
559 participants
24 months
2013-07-29
Participant Flow
A total of 559 (440 + 119) subjects received at least one dose of study drug. A total of 440 subjects (acute episode or stable on other antipsychotic) entered period II, 382 subjects completed and entered period III. An additional 119 subjects (stable on risperidone) entered period III directly. Overall 501 (382 + 119) subjects entered period III.
Subjects with an acute episode or who were stable on another antipsychotic entered Period II; Period II responders entered Period III. Subjects stable on RIS at screening entered Period III directly. Subjects who maintained response and had a stable dose of RIS LAI for the last 8 weeks of Period III were randomized to RIS LAI or placebo(Period IV).
Participant milestones
| Measure |
RISPERDAL CONSTA
risperidone long acting injectable (RIS LAI) 12.5, 25, 37.5 or 50 mg intramuscular (IM) injection every 2 weeks
|
Placebo
intramuscular (IM) injection every 2 weeks
|
Open-Label Oral Risperidone
(flexible dosage) 1 to 6 mg/day for the first 3 weeks
|
|---|---|---|---|
|
Period II (Open-Label Oral Risperidone)
STARTED
|
0
|
0
|
440
|
|
Period II (Open-Label Oral Risperidone)
COMPLETED
|
0
|
0
|
382
|
|
Period II (Open-Label Oral Risperidone)
NOT COMPLETED
|
0
|
0
|
58
|
|
Period III (Open-Label Stabilization)
STARTED
|
501
|
0
|
0
|
|
Period III (Open-Label Stabilization)
COMPLETED
|
303
|
0
|
0
|
|
Period III (Open-Label Stabilization)
NOT COMPLETED
|
198
|
0
|
0
|
|
Period IV (Double-Blind Treatment)
STARTED
|
154
|
149
|
0
|
|
Period IV (Double-Blind Treatment)
COMPLETED
|
117
|
109
|
0
|
|
Period IV (Double-Blind Treatment)
NOT COMPLETED
|
37
|
40
|
0
|
Reasons for withdrawal
| Measure |
RISPERDAL CONSTA
risperidone long acting injectable (RIS LAI) 12.5, 25, 37.5 or 50 mg intramuscular (IM) injection every 2 weeks
|
Placebo
intramuscular (IM) injection every 2 weeks
|
Open-Label Oral Risperidone
(flexible dosage) 1 to 6 mg/day for the first 3 weeks
|
|---|---|---|---|
|
Period II (Open-Label Oral Risperidone)
Death
|
0
|
0
|
1
|
|
Period II (Open-Label Oral Risperidone)
Adverse Event
|
0
|
0
|
13
|
|
Period II (Open-Label Oral Risperidone)
Non responder
|
0
|
0
|
6
|
|
Period II (Open-Label Oral Risperidone)
Ineligible to continue trial
|
0
|
0
|
7
|
|
Period II (Open-Label Oral Risperidone)
Lost to Follow-up
|
0
|
0
|
14
|
|
Period II (Open-Label Oral Risperidone)
Withdrawal by Subject
|
0
|
0
|
16
|
|
Period II (Open-Label Oral Risperidone)
Physician Decision
|
0
|
0
|
1
|
|
Period III (Open-Label Stabilization)
Death
|
2
|
0
|
0
|
|
Period III (Open-Label Stabilization)
Adverse Event
|
12
|
0
|
0
|
|
Period III (Open-Label Stabilization)
Non responder
|
107
|
0
|
0
|
|
Period III (Open-Label Stabilization)
Ineligible to continue trial
|
5
|
0
|
0
|
|
Period III (Open-Label Stabilization)
Lost to Follow-up
|
19
|
0
|
0
|
|
Period III (Open-Label Stabilization)
Withdrawal by Subject
|
49
|
0
|
0
|
|
Period III (Open-Label Stabilization)
Subject non-compliant
|
1
|
0
|
0
|
|
Period III (Open-Label Stabilization)
Physician Decision
|
1
|
0
|
0
|
|
Period III (Open-Label Stabilization)
Pregnancy
|
2
|
0
|
0
|
|
Period IV (Double-Blind Treatment)
Adverse Event
|
1
|
1
|
0
|
|
Period IV (Double-Blind Treatment)
Ineligible to continue the trial
|
4
|
4
|
0
|
|
Period IV (Double-Blind Treatment)
Lost to Follow-up
|
6
|
3
|
0
|
|
Period IV (Double-Blind Treatment)
Withdrawal by Subject
|
14
|
15
|
0
|
|
Period IV (Double-Blind Treatment)
Physician Decision
|
10
|
14
|
0
|
|
Period IV (Double-Blind Treatment)
Subject Non-compliant
|
2
|
1
|
0
|
|
Period IV (Double-Blind Treatment)
Pregnancy
|
0
|
2
|
0
|
Baseline Characteristics
A Study of the Safety and Efficacy of Injectable Risperidone in the Prevention of Bipolar Mood Episodes
Baseline characteristics by cohort
| Measure |
RISPERDAL CONSTA
n=154 Participants
risperidone long acting injectable (RIS LAI) 12.5, 25, 37.5 or 50 mg IM injection every 2 weeks
|
Placebo
n=149 Participants
IM injection every 2 weeks
|
Total
n=303 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
39.1 years
STANDARD_DEVIATION 11.81 • n=5 Participants
|
39.2 years
STANDARD_DEVIATION 12.40 • n=7 Participants
|
39.2 years
STANDARD_DEVIATION 12.08 • n=5 Participants
|
|
Sex: Female, Male
Female
|
79 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
147 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
75 Participants
n=5 Participants
|
81 Participants
n=7 Participants
|
156 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 monthsPopulation: Intention to treat. 28 subjects from a Good Clinical Practice noncompliant site and 1 site with alleged research misconduct were excluded from efficacy analyses. The median (interquartile range) for time to relapse (d): Risperdal Consta: NA (173, NA) \& Placebo: 219 (82, NA) \[NA = not available; Risperdal Consta relapse percent \< 50% \& Placebo \<75%\]
Mood Relapse was defined as: The subject met DSM-IV criteria for a manic, hypomanic, mixed, or depressive episode; or, the subject needed treatment intervention with any mood stabilizer, antipsychotic medication (other than study drug), benzodiazepine (beyond the dosage allowed), or antidepressant medication; or the subject required hospitalization for any bipolar mood episode; or the subject had a YMRS or MADRS score \>12 or a CGI-S score \>4; or a dose increase, or supplementation with oral risperidone or another antipsychotic or mood stabilizer, was needed in the opinion of the investigator.
Outcome measures
| Measure |
RISPERDAL CONSTA
n=140 Participants
risperidone long acting injectable (RIS LAI) 12.5, 25, 37.5 or 50 mg IM injection every 2 weeks
|
Placebo
n=135 Participants
IM injection every 2 weeks
|
|---|---|---|
|
Number of Participants Who Had a Mood Relapse.
Relapsed
|
42 Participants
Interval 173.0 to
|
76 Participants
Interval 82.0 to
|
|
Number of Participants Who Had a Mood Relapse.
Not Relapsed
|
98 Participants
|
59 Participants
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (last observation carried forward) of 24 month Double-Blind Period IVPopulation: Restricted to subjects with paired baseline and visit endpoint (Period IV) data only. Endpoint is the patient's last nonmissing, postbaseline value in Period IV (last observation carried forward technique)
Measure of mania; score range 0 to 60 (lower score = less severity)
Outcome measures
| Measure |
RISPERDAL CONSTA
n=135 Participants
risperidone long acting injectable (RIS LAI) 12.5, 25, 37.5 or 50 mg IM injection every 2 weeks
|
Placebo
n=133 Participants
IM injection every 2 weeks
|
|---|---|---|
|
Change in Young Mania Rating Scale (YMRS) Scores.
|
2.9 units on a scale
Standard Deviation 7.34
|
9.1 units on a scale
Standard Deviation 10.78
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (last observation carried forward) of 24 month Double-Blind Period IVPopulation: Restricted to subjects with paired baseline and visit endpoint (Period IV) data only. Endpoint is the patient's last nonmissing, postbaseline value in Period IV (last observation carried forward technique)
Measure of depression; score range 0 to 60 (lower score = less severity)
Outcome measures
| Measure |
RISPERDAL CONSTA
n=135 Participants
risperidone long acting injectable (RIS LAI) 12.5, 25, 37.5 or 50 mg IM injection every 2 weeks
|
Placebo
n=133 Participants
IM injection every 2 weeks
|
|---|---|---|
|
Change in Montgomery-Åsberg Depression Rating Scale (MADRS)
|
2.8 units on a scale
Standard Deviation 6.66
|
4.9 units on a scale
Standard Deviation 8.09
|
Adverse Events
RISPERDAL CONSTA
Placebo
Open-Label Oral Risperidone
Open Label RISPERDAL CONSTA
Serious adverse events
| Measure |
RISPERDAL CONSTA
n=154 participants at risk
Double-blind Period IV. Risperidone long acting injectable (RIS LAI) 12.5, 25, 37.5 or 50 mg intramuscular (IM) injection every 2 weeks.
|
Placebo
n=149 participants at risk
Double-blind Period IV. Intramuscular (IM) injection every 2 weeks
|
Open-Label Oral Risperidone
n=440 participants at risk
Open-label Period II. Flexible dosage. 1 to 6 mg/day for the first 3 weeks
|
Open Label RISPERDAL CONSTA
n=501 participants at risk
Open-label Period III. Risperidone long acting injectable (RIS LAI) 12.5, 25, 37.5 or 50 mg intramuscular (IM) injection every 2 weeks.
|
|---|---|---|---|---|
|
Psychiatric disorders
Depression
|
3.2%
5/154
|
0.67%
1/149
|
0.00%
0/440
|
2.0%
10/501
|
|
Psychiatric disorders
Bipolar I disorder
|
1.9%
3/154
|
6.0%
9/149
|
0.45%
2/440
|
2.4%
12/501
|
|
Psychiatric disorders
Mania
|
1.9%
3/154
|
6.7%
10/149
|
0.23%
1/440
|
0.40%
2/501
|
|
Psychiatric disorders
Bipolar disorder
|
0.00%
0/154
|
0.67%
1/149
|
0.23%
1/440
|
0.40%
2/501
|
|
Psychiatric disorders
Major depression
|
0.00%
0/154
|
0.67%
1/149
|
0.00%
0/440
|
0.00%
0/501
|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/154
|
1.3%
2/149
|
0.00%
0/440
|
0.40%
2/501
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/154
|
0.67%
1/149
|
0.23%
1/440
|
0.20%
1/501
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.65%
1/154
|
0.00%
0/149
|
0.00%
0/440
|
0.00%
0/501
|
|
Respiratory, thoracic and mediastinal disorders
Nasal polyps
|
0.65%
1/154
|
0.00%
0/149
|
0.00%
0/440
|
0.00%
0/501
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/154
|
0.67%
1/149
|
0.00%
0/440
|
0.00%
0/501
|
|
Gastrointestinal disorders
Duodenal ulcer perforation
|
0.00%
0/154
|
0.00%
0/149
|
0.23%
1/440
|
0.00%
0/501
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/154
|
0.00%
0/149
|
0.23%
1/440
|
0.00%
0/501
|
|
Gastrointestinal disorders
Peritonitis
|
0.00%
0/154
|
0.00%
0/149
|
0.23%
1/440
|
0.00%
0/501
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/154
|
0.00%
0/149
|
0.23%
1/440
|
0.00%
0/501
|
|
General disorders
Chest pain
|
0.00%
0/154
|
0.00%
0/149
|
0.23%
1/440
|
0.00%
0/501
|
|
Injury, poisoning and procedural complications
Intentional overdose
|
0.00%
0/154
|
0.00%
0/149
|
0.23%
1/440
|
0.00%
0/501
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.60%
3/501
|
|
Psychiatric disorders
Alcoholism
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.20%
1/501
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.20%
1/501
|
|
Psychiatric disorders
Completed suicide
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.20%
1/501
|
|
Psychiatric disorders
Drug dependence
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.20%
1/501
|
|
Psychiatric disorders
Hallucination, auditory
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.20%
1/501
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.20%
1/501
|
|
Psychiatric disorders
Mental disorder
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.20%
1/501
|
|
Injury, poisoning and procedural complications
Chemical poisoning
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.20%
1/501
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.20%
1/501
|
|
Injury, poisoning and procedural complications
Hepatic rupture
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.20%
1/501
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.20%
1/501
|
|
Injury, poisoning and procedural complications
Multiple injuries
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.20%
1/501
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.20%
1/501
|
|
Injury, poisoning and procedural complications
Ulna fracture
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.20%
1/501
|
|
General disorders
Accidental death
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.20%
1/501
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.20%
1/501
|
|
Infections and infestations
Pneumonia
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.20%
1/501
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/154
|
0.00%
0/149
|
0.00%
0/440
|
0.20%
1/501
|
Other adverse events
| Measure |
RISPERDAL CONSTA
n=154 participants at risk
Double-blind Period IV. Risperidone long acting injectable (RIS LAI) 12.5, 25, 37.5 or 50 mg intramuscular (IM) injection every 2 weeks.
|
Placebo
n=149 participants at risk
Double-blind Period IV. Intramuscular (IM) injection every 2 weeks
|
Open-Label Oral Risperidone
n=440 participants at risk
Open-label Period II. Flexible dosage. 1 to 6 mg/day for the first 3 weeks
|
Open Label RISPERDAL CONSTA
n=501 participants at risk
Open-label Period III. Risperidone long acting injectable (RIS LAI) 12.5, 25, 37.5 or 50 mg intramuscular (IM) injection every 2 weeks.
|
|---|---|---|---|---|
|
Nervous system disorders
Headache
|
7.1%
11/154
|
6.7%
10/149
|
7.5%
33/440
|
5.6%
28/501
|
|
Nervous system disorders
Sommolence
|
0.65%
1/154
|
0.67%
1/149
|
5.5%
24/440
|
2.6%
13/501
|
|
Psychiatric disorders
Insomnia
|
7.8%
12/154
|
6.0%
9/149
|
5.2%
23/440
|
13.2%
66/501
|
|
Psychiatric disorders
Anxiety
|
2.6%
4/154
|
4.0%
6/149
|
1.4%
6/440
|
4.6%
23/501
|
|
Psychiatric disorders
Agitation
|
1.3%
2/154
|
4.7%
7/149
|
1.1%
5/440
|
5.6%
28/501
|
|
Investigations
Weight increased
|
4.5%
7/154
|
0.67%
1/149
|
0.68%
3/440
|
5.4%
27/501
|
Additional Information
Director of Clinical Research
Johnson & Johnson Pharmaceutical Research and Development
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60