Phase 2
N=45
Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetic/Efficacy
Schizophrenia
Bottom Line
View on ClinicalTrials.gov: NCT01677377 ↗Enrolled (actual)
45
Serious AEs
2.2%
Results posted
Oct 2018
Primary outcome: Primary: Summary of Participants With Treatment-Emergent Adverse Events (TEAE) — 4; 4; 7; 11 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Risperidone (Drug); RBP-7000 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Indivior Inc.
- Primary completion
- Apr 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Summary of Participants With Treatment-Emergent Adverse Events (TEAE) |
4; 4; 7; 11; 11; 8 | — |
| PRIMARY Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) |
335.4; 437.5; 466.2; 276.5; 415.1; 497.5 | — |
| PRIMARY Total Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak |
16.343; 19.415; 24.400; 14.549; 16.973; 22.852 | — |
| PRIMARY Total Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak |
6.000; 6.000; 6.000; 17.917; 24.000; 24.000 | — |
| PRIMARY Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) |
6506.0; 8293.8; 12594.7; 8567.1; 11047.7; 15982.6 | — |
| PRIMARY Total Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile |
9.682; 12.342; 18.742; 12.749; 16.440; 23.784 | — |
| PRIMARY Total Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile |
16.878; 22.825; 32.235; 17.885; 30.804; 38.300 | — |
| PRIMARY Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile |
4.867; 5.642; 9.159; 5.028; 10.534; 11.938 | — |
| PRIMARY Total Risperidone PK: Percent Fluctuation Over the PK Profile |
151.211; 135.238; 153.386; 108.226; 102.396; 114.008 | — |
| PRIMARY Total Risperidone PK: Swing Over the PK Profile |
2.502; 2.150; 2.928; 2.588; 2.052; 2.019 | — |
| PRIMARY Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile |
168.000; 215.833; 192.000; 216.00; 264.067; 216.000 | — |
| PRIMARY Total Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC)) |
1.1; 1.6; 1.2 | — |
| PRIMARY Total Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax)) |
0.976; 1.525; 1.105 | — |
| PRIMARY Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) |
6186.9; 7735.1; 10001.4; 8236.4; 10988.6; 15484.3 | — |
| PRIMARY Total Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) |
9.548; 11.937; 15.434; 12.710; 16.958; 23.896 | — |
| PRIMARY Total Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) |
16.867; 21.415; 32.235; 17.885; 30.804; 38.300 | — |
| PRIMARY Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak |
4.867; 5.642; 9.159; 5.028; 10.534; 13.735 | — |
| PRIMARY Total Risperidone PK: Percent Fluctuation Over the Secondary Peak |
122.350; 122.042; 151.294; 101.788; 101.666; 96.489 | — |
| PRIMARY Total Risperidone PK: Swing Over the Secondary Peak |
2.048; 2.017; 2.928; 2.412; 1.914; 1.679 | — |
| PRIMARY Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak |
168.000; 264.000; 192.000; 228.000; 264.067; 216.000 | — |
| PRIMARY Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) |
103.8; 87.8; 99.5; 98.7; 107.1; 127.0 | — |
| PRIMARY Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak |
6.280; 5.460; 6.470; 4.955; 6.680; 7.145 | — |
| PRIMARY Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak |
6.000; 6.000; 4.000; 6.000; 6.000; 4.483 | — |
| PRIMARY Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) |
1250.9; 1663.4; 3099.4; 2144.6; 2647.1; 3621.2 | — |
| PRIMARY Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile |
1.861; 2.475; 4.612; 3.191; 3.939; 5.389 | — |
| PRIMARY Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile |
6.280; 7.520; 9.270; 5.720; 7.490; 12.125 | — |
| PRIMARY Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile |
0.829; 1.060; 1.720; 1.230; 2.100; 2.415 | — |
| PRIMARY Risperidone PK: Percent Fluctuation Over the PK Profile |
190.745; 215.048; 173.609; 147.252; 140.688; 143.652 | — |
| PRIMARY Risperidone PK: Swing Over the PK Profile |
4.575; 4.151; 4.938; 4.077; 2.863; 3.159 | — |
| PRIMARY Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile |
6.000; 168.000; 192.000; 18.000; 192.000; 180.000 | — |
| PRIMARY Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC)) |
1.1; 1.7; 1.1 | — |
| PRIMARY Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax)) |
1.049; 1.214; 1.155 | — |
| PRIMARY Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) |
1198.2; 1544.9; 2937.3; 2204.6; 2494.8; 3476.6 | — |
| PRIMARY Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) |
1.849; 2.384; 4.533; 3.402; 3.850; 5.365 | — |
| PRIMARY Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) |
3.120; 5.950; 7.950; 5.220; 7.010; 12.125 | — |
| PRIMARY Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak |
0.829; 1.070; 1.720; 1.230; 2.100; 2.415 | — |
| PRIMARY Risperidone PK: Percent Fluctuation Over the Secondary Peak |
134.805; 134.898; 141.030; 136.691; 125.387; 138.380 | — |
| PRIMARY Risperidone PK: Swing Over the Secondary Peak |
2.644; 2.680; 3.813; 3.736; 2.652; 2.698 | — |
| PRIMARY Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak |
120.000; 216.000; 192.000; 204.000; 216.00; 180.000 | — |
| PRIMARY 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) |
237.0; 251.1; 404.8; 169.2; 263.4; 342.6 | — |
| PRIMARY 9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak |
11.100; 12.900; 17.500; 9.470; 12.900; 17.450 | — |
| PRIMARY 9-hydroxyrisperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak |
4.000; 6.000; 6.000; 24.000; 24.000; 24.000 | — |
| PRIMARY 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau) |
4927.0; 5607.5; 9862.2; 5538.3; 8546.7; 11666.9 | — |
| PRIMARY 9-hydroxyrisperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile |
7.332; 8.344; 14.676; 8.242; 12.718; 17.361 | — |
| PRIMARY 9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile |
12.300; 15.600; 22.400; 13.450; 21.200; 29.600 | — |
| PRIMARY 9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile |
3.940; 4.240; 6.690; 4.180; 6.580; 8.365 | — |
| PRIMARY 9-hydroxyrisperidone PK: Percent Fluctuation Over the PK Profile |
120.024; 124.696; 142.828; 121.077; 106.728; 122.701 | — |
| PRIMARY 9-hydroxyrisperidone PK: Swing Over the PK Profile |
1.984; 2.041; 2.633; 2.901; 2.142; 2.240 | — |
| PRIMARY 9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile |
168.000; 168.000; 192.000; 216.000; 264.000; 216.000 | — |
| PRIMARY 9-hydroxyrisperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC)) |
1.1; 1.5; 1.2 | — |
| PRIMARY 9-hydroxyrisperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax)) |
0.997; 1.442; 1.076 | — |
| PRIMARY 9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29) |
4696.8; 5222.9; 7891.0; 5388.2; 8311.7; 11786.5 | — |
| PRIMARY 9-hydroxyrisperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29) |
7.248; 8.060; 12.177; 8.315; 12.827; 18.189 | — |
| PRIMARY 9-hydroxyrisperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax) |
12.300; 15.600; 22.300; 13.450; 21.200; 29.600 | — |
| PRIMARY 9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak |
3.940; 4.250; 7.060; 4.180; 7.660; 11.450 | — |
| PRIMARY 9-hydroxyrisperidone PK: Percent Fluctuation Over the Secondary Peak |
112.945; 127.274; 141.300; 106.055; 104.207; 101.956 | — |
| PRIMARY 9-hydroxyrisperidone PK: Swing Over the Secondary Peak |
1.936; 2.041; 2.633; 2.018; 1.991; 1.595 | — |
| PRIMARY 9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak |
216.000; 168.000; 216.000; 228.000; 264.000; 216.000 | — |
| SECONDARY Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106 |
27.0; 24.0; 27.0; 13.0; 14.0; 13.0 | — |
| SECONDARY Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106 |
3.0; 3.0; 3.0; 3.0; 3.0; 3.0 | — |
| SECONDARY Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106 |
1.0; 0.0; 1.0; 1.0; 0.0; 1.0 | — |
| SECONDARY Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106 |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106 |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Participants With Suicidal Ideation or Behavior as Identified Using the Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Baseline and Days 28, 56, 84 and 106 |
0; 0; 0; 0; 1; 1 | — |
Summary
Evaluate the safety and tolerability of multiple subcutaneous injections of various dosages of risperidone with clinically stable schizophrenia
Eligibility Criteria
Inclusion Criteria
- Male and female
- > 18 to 5 years
- Subjects with another active medical condition or organ disease that may either compromise subject safety and/or outcome evaluation of the study drug
- Subjects with evidence or history of a significant hepatic disorder that may either compromise subject safety or interfere with the safety and/or outcome evaluation of the study drug. Individuals with acute hepatitis (including but not limited to B or C); or individuals with 1) total bilirubin >1.5x the upper limit of normal and/or 2) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2x upper limit of normal (ULN) will be excluded
- Subjects with hepatitis C antibody and AST, ALT, or alkaline phosphatase >2x and total bilirubin >1.3 mg/dL will be excluded
- Subjects with a history of renal disease, or a creatinine clearance of less than 80 mL/min (as determined by the Cockcroft Gault formula)
- Subjects with an international normalized ratio >2.0 at screening
- Subjects with corrected QT interval (Bazett's - QTcB) >450 msec (male) or >470 msec (female) at screening. Subjects with a QTc above these levels due to a benign right bundle branch block can be included in the study at the discretion of the PI
- Subjects who are known to have AIDS or to be HIV positive
- Subjects with suicidal ideation with intent and plan (Columbia-Suicide Severity Rating Scale (C-SSRS) affirmative answers to questions 4 and 5 of the ideation section) or suicide attempts within the last six months as noted on the C-SSRS, or subjects with uncontrolled depression in the opinion of the investigator
- Subjects with known diagnosis of type 1 or 2 diabetes or subjects with Hemoglobin A1c >7.0 at screening
- Subjects who have participated in a clinical trial within 30 days prior to study screening
- Subjects who meet the DSM-IV-TR criteria for alcohol abuse or dependence within the last six months of screening
Data sourced from ClinicalTrials.gov (NCT01677377). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.