Trial Outcomes & Findings for Randomized, Double-blind, Placebo Controlled, Multi-center and Tolerability of RBP-7000 in Schizophrenia Patients (NCT NCT02109562)
NCT ID: NCT02109562
Last Updated: 2018-10-26
Results Overview
The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor judgement, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score is the sum of all 30 PANSS items and ranges from 30 to 210, with 30 indicating absence of symptoms of schizophrenia and 210 indicating extreme ratings of all 30 symptoms. Negative change from baseline scores indicate improvements in symptoms. Estimates (least square means and standard errors), 2-sided confidence intervals, and -1-sided P values are based on a repeated-measures linear regression model of the change from baseline score, with fixed effects for visit as a categorical variable, baseline score, treatment and treatment by visit interaction, assuming an unstructured covariance matrix.
COMPLETED
PHASE3
354 participants
Day 1 prior to treatment (Baseline), Days 15, 29, 43 and 57 or early discontinuation
2018-10-26
Participant Flow
A total of 538 subjects were screened for study participation at 33 sites in the US, including 354 subjects randomly assigned to treatment. Four subjects were found to be randomized incorrectly; therefore, they were withdrawn from the study and did not receive study drug (counted as 'Physician Decision' for reason d/c below).
Participant milestones
| Measure |
RBP-7000 90 mg
Risperidone tablets given during the screening period to check for sensitivity. RBP-7000 administered as a 90 mg subcutaneous injection on Days 1 and 29 for a total of two injections.
|
RBP-7000 120 mg
Risperidone tablets given during the screening period to check for sensitivity. RBP-7000 administered as a 120 mg subcutaneous injection on Days 1 and 29 for a total of two injections.
|
Placebo
Risperidone tablets given during the screening period to check for sensitivity. Placebo administered by subcutaneous injection on Days 1 and 29 for a total of two injections.
|
|---|---|---|---|
|
Overall Study
STARTED
|
116
|
119
|
119
|
|
Overall Study
Safety
|
115
|
117
|
118
|
|
Overall Study
Intent to Treat (ITT)
|
111
|
114
|
112
|
|
Overall Study
COMPLETED
|
90
|
85
|
84
|
|
Overall Study
NOT COMPLETED
|
26
|
34
|
35
|
Reasons for withdrawal
| Measure |
RBP-7000 90 mg
Risperidone tablets given during the screening period to check for sensitivity. RBP-7000 administered as a 90 mg subcutaneous injection on Days 1 and 29 for a total of two injections.
|
RBP-7000 120 mg
Risperidone tablets given during the screening period to check for sensitivity. RBP-7000 administered as a 120 mg subcutaneous injection on Days 1 and 29 for a total of two injections.
|
Placebo
Risperidone tablets given during the screening period to check for sensitivity. Placebo administered by subcutaneous injection on Days 1 and 29 for a total of two injections.
|
|---|---|---|---|
|
Overall Study
Insufficient clinical response
|
2
|
0
|
4
|
|
Overall Study
Adverse Event
|
0
|
2
|
3
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
1
|
|
Overall Study
Protocol Violation
|
0
|
3
|
1
|
|
Overall Study
Withdrawal by Subject
|
20
|
25
|
21
|
|
Overall Study
Physician Decision
|
3
|
4
|
5
|
Baseline Characteristics
Randomized, Double-blind, Placebo Controlled, Multi-center and Tolerability of RBP-7000 in Schizophrenia Patients
Baseline characteristics by cohort
| Measure |
RBP-7000 90 mg
n=115 Participants
Risperidone tablets given during the screening period to check for sensitivity. RBP-7000 administered as a 90 mg subcutaneous injection on Days 1 and 29 for a total of two injections.
|
RBP-7000 120 mg
n=117 Participants
Risperidone tablets given during the screening period to check for sensitivity. RBP-7000 administered as a 120 mg subcutaneous injection on Days 1 and 29 for a total of two injections.
|
Placebo
n=118 Participants
Risperidone tablets given during the screening period to check for sensitivity. Placebo administered by subcutaneous injection on Days 1 and 29 for a total of two injections.
|
Total
n=350 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
40.5 years
STANDARD_DEVIATION 9.41 • n=93 Participants
|
40.6 years
STANDARD_DEVIATION 9.45 • n=4 Participants
|
42.4 years
STANDARD_DEVIATION 9.07 • n=27 Participants
|
41.1 years
STANDARD_DEVIATION 9.33 • n=483 Participants
|
|
Age, Customized
20 years and under
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
|
Age, Customized
21 to 30 years
|
16 Participants
n=93 Participants
|
20 Participants
n=4 Participants
|
16 Participants
n=27 Participants
|
52 Participants
n=483 Participants
|
|
Age, Customized
31 to 40 years
|
38 Participants
n=93 Participants
|
32 Participants
n=4 Participants
|
28 Participants
n=27 Participants
|
98 Participants
n=483 Participants
|
|
Age, Customized
41 to 50 years
|
41 Participants
n=93 Participants
|
43 Participants
n=4 Participants
|
49 Participants
n=27 Participants
|
133 Participants
n=483 Participants
|
|
Age, Customized
51 to 55 years
|
19 Participants
n=93 Participants
|
20 Participants
n=4 Participants
|
24 Participants
n=27 Participants
|
63 Participants
n=483 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=93 Participants
|
31 Participants
n=4 Participants
|
31 Participants
n=27 Participants
|
82 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
95 Participants
n=93 Participants
|
86 Participants
n=4 Participants
|
87 Participants
n=27 Participants
|
268 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
10 Participants
n=27 Participants
|
26 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
108 Participants
n=93 Participants
|
107 Participants
n=4 Participants
|
107 Participants
n=27 Participants
|
322 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
White
|
28 Participants
n=93 Participants
|
30 Participants
n=4 Participants
|
27 Participants
n=27 Participants
|
85 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
83 Participants
n=93 Participants
|
83 Participants
n=4 Participants
|
88 Participants
n=27 Participants
|
254 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
|
Weight
|
90.60 kg
STANDARD_DEVIATION 18.895 • n=93 Participants
|
89.01 kg
STANDARD_DEVIATION 20.462 • n=4 Participants
|
91.84 kg
STANDARD_DEVIATION 22.885 • n=27 Participants
|
90.49 kg
STANDARD_DEVIATION 20.802 • n=483 Participants
|
|
Height
|
175.1 cm
STANDARD_DEVIATION 9.09 • n=93 Participants
|
174.3 cm
STANDARD_DEVIATION 9.95 • n=4 Participants
|
173.1 cm
STANDARD_DEVIATION 10.91 • n=27 Participants
|
174.1 cm
STANDARD_DEVIATION 10.02 • n=483 Participants
|
|
Body Mass Index
|
29.576 kg/m^2
STANDARD_DEVIATION 5.938 • n=93 Participants
|
29.376 kg/m^2
STANDARD_DEVIATION 6.664 • n=4 Participants
|
30.706 kg/m^2
STANDARD_DEVIATION 7.293 • n=27 Participants
|
29.890 kg/m^2
STANDARD_DEVIATION 6.667 • n=483 Participants
|
|
Waist-to-Hip Ratio
|
0.947 ratio
STANDARD_DEVIATION 0.078 • n=93 Participants
|
0.936 ratio
STANDARD_DEVIATION 0.072 • n=4 Participants
|
0.944 ratio
STANDARD_DEVIATION 0.090 • n=27 Participants
|
0.942 ratio
STANDARD_DEVIATION 0.080 • n=483 Participants
|
|
Previous Antipsychotic Treatment
Yes
|
114 Participants
n=93 Participants
|
116 Participants
n=4 Participants
|
118 Participants
n=27 Participants
|
348 Participants
n=483 Participants
|
|
Previous Antipsychotic Treatment
No
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
|
Age at First Schizophrenia Diagnosis
|
25.5 years
STANDARD_DEVIATION 8.21 • n=93 Participants
|
26.9 years
STANDARD_DEVIATION 8.48 • n=4 Participants
|
26.6 years
STANDARD_DEVIATION 9.25 • n=27 Participants
|
26.3 years
STANDARD_DEVIATION 8.66 • n=483 Participants
|
PRIMARY outcome
Timeframe: Day 1 prior to treatment (Baseline), Days 15, 29, 43 and 57 or early discontinuationPopulation: Intent to treat (ITT) population
The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor judgement, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score is the sum of all 30 PANSS items and ranges from 30 to 210, with 30 indicating absence of symptoms of schizophrenia and 210 indicating extreme ratings of all 30 symptoms. Negative change from baseline scores indicate improvements in symptoms. Estimates (least square means and standard errors), 2-sided confidence intervals, and -1-sided P values are based on a repeated-measures linear regression model of the change from baseline score, with fixed effects for visit as a categorical variable, baseline score, treatment and treatment by visit interaction, assuming an unstructured covariance matrix.
Outcome measures
| Measure |
RBP-7000 90 mg
n=111 Participants
Risperidone tablets given during the screening period to check for sensitivity. RBP-7000 administered as a 90 mg subcutaneous injection on Days 1 and 29 for a total of two injections.
|
RBP-7000 120 mg
n=114 Participants
Risperidone tablets given during the screening period to check for sensitivity. RBP-7000 administered as a 120 mg subcutaneous injection on Days 1 and 29 for a total of two injections.
|
Placebo
n=112 Participants
Risperidone tablets given during the screening period to check for sensitivity. Placebo administered by subcutaneous injection on Days 1 and 29 for a total of two injections.
|
|---|---|---|---|
|
Mixed Model for Repeated Measures (MMRM) Analysis of Change From Baseline to End of Treatment in the Positive and Negative Syndrome Scale (PANSS) Total Score
|
-15.367 units on a scale
Standard Error 1.2230
|
-16.456 units on a scale
Standard Error 1.2073
|
-9.219 units on a scale
Standard Error 1.2162
|
SECONDARY outcome
Timeframe: Day 1 prior to treatment (Baseline), Days 15, 29, 43 and 57 or early discontinuationPopulation: Intent to treat population (ITT)
The CGI-S rating scale is a 7-point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants". Negative change from baseline scores indicate improvement in the severity of illness. Estimates (least square means and standard errors), 2-sided confidence intervals, and -1-sided P values are based on a repeated-measures linear regression model of the change from baseline score, with fixed effects for visit as a categorical variable, baseline score, treatment and treatment by visit interaction, assuming an unstructured covariance matrix.
Outcome measures
| Measure |
RBP-7000 90 mg
n=111 Participants
Risperidone tablets given during the screening period to check for sensitivity. RBP-7000 administered as a 90 mg subcutaneous injection on Days 1 and 29 for a total of two injections.
|
RBP-7000 120 mg
n=114 Participants
Risperidone tablets given during the screening period to check for sensitivity. RBP-7000 administered as a 120 mg subcutaneous injection on Days 1 and 29 for a total of two injections.
|
Placebo
n=112 Participants
Risperidone tablets given during the screening period to check for sensitivity. Placebo administered by subcutaneous injection on Days 1 and 29 for a total of two injections.
|
|---|---|---|---|
|
Mixed Model for Repeated Measures (MMRM) Analysis of Change From Baseline to End of Treatment in Clinical Global Impression - Severity Scale (CGI-S)
|
-0.868 units on a scale
Standard Error 0.0662
|
-0.914 units on a scale
Standard Error 0.0654
|
-0.518 units on a scale
Standard Error 0.0659
|
SECONDARY outcome
Timeframe: Day 1 to Week 8Population: Safety population
An adverse event (AE) is defined as any study-related event that represents a change (positive or negative) in frequency or severity from a baseline (prestudy) event (if any), regardless of the presence of causal relationship or medical significance. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the first study dose date. AEs are determined by the Investigator to be related or not related to the study drug. A serious AE (SAE) is defined by federal regulation as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Although a subject may have had 2 or more adverse experiences the subject is counted only once in a category. The same subject may appear in different categories.
Outcome measures
| Measure |
RBP-7000 90 mg
n=115 Participants
Risperidone tablets given during the screening period to check for sensitivity. RBP-7000 administered as a 90 mg subcutaneous injection on Days 1 and 29 for a total of two injections.
|
RBP-7000 120 mg
n=117 Participants
Risperidone tablets given during the screening period to check for sensitivity. RBP-7000 administered as a 120 mg subcutaneous injection on Days 1 and 29 for a total of two injections.
|
Placebo
n=118 Participants
Risperidone tablets given during the screening period to check for sensitivity. Placebo administered by subcutaneous injection on Days 1 and 29 for a total of two injections.
|
|---|---|---|---|
|
Summary of Participants With Treatment-Emergent Adverse Events (TEAE)
No TEAEs
|
34 Participants
|
26 Participants
|
37 Participants
|
|
Summary of Participants With Treatment-Emergent Adverse Events (TEAE)
1 or more TEAEs
|
81 Participants
|
91 Participants
|
81 Participants
|
|
Summary of Participants With Treatment-Emergent Adverse Events (TEAE)
Related TEAE
|
58 Participants
|
65 Participants
|
50 Participants
|
|
Summary of Participants With Treatment-Emergent Adverse Events (TEAE)
Serious TEAE
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Summary of Participants With Treatment-Emergent Adverse Events (TEAE)
Serious, related TEAE
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Summary of Participants With Treatment-Emergent Adverse Events (TEAE)
TEAE causing discontinuation
|
0 Participants
|
2 Participants
|
3 Participants
|
|
Summary of Participants With Treatment-Emergent Adverse Events (TEAE)
Death
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
RBP-7000 90 mg
RBP-7000 120 mg
Placebo
Serious adverse events
| Measure |
RBP-7000 90 mg
n=115 participants at risk
Risperidone tablets given during the screening period to check for sensitivity. RBP-7000 administered as a 90 mg subcutaneous injection on Days 1 and 29 for a total of two injections.
|
RBP-7000 120 mg
n=117 participants at risk
Risperidone tablets given during the screening period to check for sensitivity. RBP-7000 administered as a 120 mg subcutaneous injection on Days 1 and 29 for a total of two injections.
|
Placebo
n=118 participants at risk
Risperidone tablets given during the screening period to check for sensitivity. Placebo administered by subcutaneous injection on Days 1 and 29 for a total of two injections.
|
|---|---|---|---|
|
General disorders
Chest pain
|
0.00%
0/115 • Day 1 to Week 8
|
0.85%
1/117 • Day 1 to Week 8
|
0.00%
0/118 • Day 1 to Week 8
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/115 • Day 1 to Week 8
|
0.00%
0/117 • Day 1 to Week 8
|
0.85%
1/118 • Day 1 to Week 8
|
Other adverse events
| Measure |
RBP-7000 90 mg
n=115 participants at risk
Risperidone tablets given during the screening period to check for sensitivity. RBP-7000 administered as a 90 mg subcutaneous injection on Days 1 and 29 for a total of two injections.
|
RBP-7000 120 mg
n=117 participants at risk
Risperidone tablets given during the screening period to check for sensitivity. RBP-7000 administered as a 120 mg subcutaneous injection on Days 1 and 29 for a total of two injections.
|
Placebo
n=118 participants at risk
Risperidone tablets given during the screening period to check for sensitivity. Placebo administered by subcutaneous injection on Days 1 and 29 for a total of two injections.
|
|---|---|---|---|
|
General disorders
Injection site pain
|
15.7%
18/115 • Day 1 to Week 8
|
22.2%
26/117 • Day 1 to Week 8
|
19.5%
23/118 • Day 1 to Week 8
|
|
Nervous system disorders
Headache
|
17.4%
20/115 • Day 1 to Week 8
|
15.4%
18/117 • Day 1 to Week 8
|
23.7%
28/118 • Day 1 to Week 8
|
|
Investigations
Weight increased
|
13.0%
15/115 • Day 1 to Week 8
|
12.8%
15/117 • Day 1 to Week 8
|
3.4%
4/118 • Day 1 to Week 8
|
|
Gastrointestinal disorders
Constipation
|
7.0%
8/115 • Day 1 to Week 8
|
7.7%
9/117 • Day 1 to Week 8
|
5.1%
6/118 • Day 1 to Week 8
|
|
Gastrointestinal disorders
Toothache
|
7.8%
9/115 • Day 1 to Week 8
|
6.8%
8/117 • Day 1 to Week 8
|
5.9%
7/118 • Day 1 to Week 8
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.5%
4/115 • Day 1 to Week 8
|
6.8%
8/117 • Day 1 to Week 8
|
4.2%
5/118 • Day 1 to Week 8
|
|
General disorders
Injection site erythema
|
6.1%
7/115 • Day 1 to Week 8
|
4.3%
5/117 • Day 1 to Week 8
|
5.1%
6/118 • Day 1 to Week 8
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.2%
6/115 • Day 1 to Week 8
|
5.1%
6/117 • Day 1 to Week 8
|
2.5%
3/118 • Day 1 to Week 8
|
|
Nervous system disorders
Akathisia
|
2.6%
3/115 • Day 1 to Week 8
|
6.8%
8/117 • Day 1 to Week 8
|
4.2%
5/118 • Day 1 to Week 8
|
|
Psychiatric disorders
Anxiety
|
2.6%
3/115 • Day 1 to Week 8
|
6.8%
8/117 • Day 1 to Week 8
|
5.1%
6/118 • Day 1 to Week 8
|
|
Gastrointestinal disorders
Dyspepsia
|
3.5%
4/115 • Day 1 to Week 8
|
6.0%
7/117 • Day 1 to Week 8
|
9.3%
11/118 • Day 1 to Week 8
|
|
Gastrointestinal disorders
Nausea
|
4.3%
5/115 • Day 1 to Week 8
|
5.1%
6/117 • Day 1 to Week 8
|
8.5%
10/118 • Day 1 to Week 8
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.2%
6/115 • Day 1 to Week 8
|
4.3%
5/117 • Day 1 to Week 8
|
7.6%
9/118 • Day 1 to Week 8
|
|
Nervous system disorders
Somnolence
|
5.2%
6/115 • Day 1 to Week 8
|
4.3%
5/117 • Day 1 to Week 8
|
0.00%
0/118 • Day 1 to Week 8
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.87%
1/115 • Day 1 to Week 8
|
7.7%
9/117 • Day 1 to Week 8
|
5.1%
6/118 • Day 1 to Week 8
|
|
Psychiatric disorders
Insomnia
|
3.5%
4/115 • Day 1 to Week 8
|
2.6%
3/117 • Day 1 to Week 8
|
5.9%
7/118 • Day 1 to Week 8
|
|
General disorders
Nodule
|
2.6%
3/115 • Day 1 to Week 8
|
3.4%
4/117 • Day 1 to Week 8
|
5.1%
6/118 • Day 1 to Week 8
|
Additional Information
Global Director, Clinical Development
Indivior, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee Proposed publications shall be submitted to Sponsor 30 days prior to submission for publication, and may be withheld for an additional period, up to 90 days, to allow Sponsor to file patent applications. If a multicenter publication isn't submitted for publication within 12 months of the conclusion of the Study at all sites, or is published in a shorter period, the results from the institution's site may be published individually.
- Publication restrictions are in place
Restriction type: OTHER