Trial Outcomes & Findings for Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetic/Efficacy (NCT NCT01677377)
NCT ID: NCT01677377
Last Updated: 2018-10-23
Results Overview
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.
COMPLETED
PHASE2
45 participants
Day 1 to Day 106
2018-10-23
Participant Flow
This was an open-label, Phase 2A, multiple-ascending dose study performed at 2 sites in the U.S. Seventy subjects were screened and 45 subjects were enrolled and received RBP-7000.
Participant milestones
| Measure |
Cohort 1, RBP-7000 60 mg
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
Cohort 3, RBP-7000 120 mg
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Overall Study
STARTED
|
15
|
15
|
15
|
|
Overall Study
COMPLETED
|
14
|
14
|
9
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
6
|
Reasons for withdrawal
| Measure |
Cohort 1, RBP-7000 60 mg
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
Cohort 3, RBP-7000 120 mg
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Overall Study
Protocol Violation
|
1
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
3
|
|
Overall Study
Lack of Efficacy
|
0
|
0
|
1
|
|
Overall Study
Pregnancy
|
0
|
0
|
1
|
Baseline Characteristics
Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetic/Efficacy
Baseline characteristics by cohort
| Measure |
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Total
n=45 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Age, Continuous
|
43.7 years
STANDARD_DEVIATION 9.98 • n=5 Participants
|
42.5 years
STANDARD_DEVIATION 9.93 • n=7 Participants
|
41.7 years
STANDARD_DEVIATION 7.96 • n=5 Participants
|
42.6 years
STANDARD_DEVIATION 9.16 • n=4 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
33 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
14 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
42 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
7 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
28 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Weight
|
83.76 kg
STANDARD_DEVIATION 16.279 • n=5 Participants
|
84.07 kg
STANDARD_DEVIATION 13.707 • n=7 Participants
|
92.63 kg
STANDARD_DEVIATION 14.075 • n=5 Participants
|
86.82 kg
STANDARD_DEVIATION 14.980 • n=4 Participants
|
|
Height
|
172.19 cm
STANDARD_DEVIATION 8.731 • n=5 Participants
|
175.50 cm
STANDARD_DEVIATION 11.137 • n=7 Participants
|
174.41 cm
STANDARD_DEVIATION 8.346 • n=5 Participants
|
174.03 cm
STANDARD_DEVIATION 9.372 • n=4 Participants
|
|
Body Mass Index
|
28.13 kg/m^2
STANDARD_DEVIATION 4.487 • n=5 Participants
|
27.35 kg/m^2
STANDARD_DEVIATION 4.176 • n=7 Participants
|
30.43 kg/m^2
STANDARD_DEVIATION 3.911 • n=5 Participants
|
28.64 kg/m^2
STANDARD_DEVIATION 4.309 • n=4 Participants
|
|
Cytochrome P450 2D6 (CYP-2D6)
Intermediate
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Cytochrome P450 2D6 (CYP-2D6)
Poor
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Cytochrome P450 2D6 (CYP-2D6)
Extensive
|
11 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
39 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Day 1 to Day 106Population: 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 |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Summary of Participants With Treatment-Emergent Adverse Events (TEAE)
No TEAEs
|
7 Participants
|
4 Participants
|
4 Participants
|
|
Summary of Participants With Treatment-Emergent Adverse Events (TEAE)
Serious TEAEs
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Summary of Participants With Treatment-Emergent Adverse Events (TEAE)
TEAE causing discontinuation
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Summary of Participants With Treatment-Emergent Adverse Events (TEAE)
1 or more TEAEs
|
8 Participants
|
11 Participants
|
11 Participants
|
|
Summary of Participants With Treatment-Emergent Adverse Events (TEAE)
Related TEAEs
|
4 Participants
|
6 Participants
|
11 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)
Death
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1-2, Day 57-58Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] AUC0-24 calculated using the linear trapezoidal rule. Results are reported across two timeframes: * Initial Peak, Injection 1 (Day 1 injection to 24 hours after injection) * Initial Peak, Injection 3 (Day 57 injection to 24 hours after injection) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24)
Initial Peak, Injection 1
|
466.2 hr*ng/mL
Interval 193.6 to 872.0
|
335.4 hr*ng/mL
Interval 178.4 to 874.4
|
437.5 hr*ng/mL
Interval 203.2 to 942.3
|
|
Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24)
Initial Peak, Injection 3
|
497.5 hr*ng/mL
Interval 304.9 to 788.2
|
276.5 hr*ng/mL
Interval 113.3 to 821.6
|
415.1 hr*ng/mL
Interval 151.4 to 697.0
|
PRIMARY outcome
Timeframe: Day 1-2, Day 57-58Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Cmax determined directly from individual concentration-time data. Results are reported across two timeframes: * Initial Peak, Injection 1 (Day 1 injection to 24 hours after injection) * Initial Peak, Injection 3 (Day 57 injection to 24 hours after injection) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak
Initial Peak, Injection 1
|
24.400 ng/mL
Interval 9.0 to 42.71
|
16.343 ng/mL
Interval 8.49 to 45.33
|
19.415 ng/mL
Interval 9.88 to 41.14
|
|
Total Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak
Initial Peak, Injection 3
|
22.852 ng/mL
Interval 13.35 to 39.17
|
14.549 ng/mL
Interval 5.71 to 37.66
|
16.973 ng/mL
Interval 7.06 to 39.44
|
PRIMARY outcome
Timeframe: Day 1-2, Day 57-58Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Tmax determined directly from individual concentration-time data. Results are reported across two timeframes: * Initial Peak, Injection 1 (Day 1 injection to 24 hours after injection) * Initial Peak, Injection 3 (Day 57 injection to 24 hours after injection) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak
Initial Peak, Injection 1
|
6.000 hours
Interval 2.0 to 24.0
|
6.000 hours
Interval 3.0 to 23.83
|
6.000 hours
Interval 2.0 to 12.02
|
|
Total Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak
Initial Peak, Injection 3
|
24.000 hours
Interval 6.0 to 24.0
|
17.917 hours
Interval 6.0 to 24.0
|
24.000 hours
Interval 3.0 to 24.08
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] AUCtau calculated using the linear trapezoidal rule. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau)
Overall, Injection 3
|
15982.6 hr*ng/mL
Interval 10256.6 to 18661.0
|
8567.1 hr*ng/mL
Interval 3890.3 to 17097.5
|
11047.7 hr*ng/mL
Interval 7197.5 to 22067.1
|
|
Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau)
Overall, Injection 1
|
12594.7 hr*ng/mL
Interval 7894.8 to 17498.4
|
6506.0 hr*ng/mL
Interval 2400.2 to 16817.9
|
8293.8 hr*ng/mL
Interval 3680.3 to 19454.6
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] The average of plasma concentrations calculated as AUCtau/ tau (tau = 28 days) Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile
Overall, Injection 1
|
18.742 ng/mL
Interval 11.75 to 26.04
|
9.682 ng/mL
Interval 3.57 to 25.03
|
12.342 ng/mL
Interval 5.48 to 28.95
|
|
Total Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile
Overall, Injection 3
|
23.784 ng/mL
Interval 15.26 to 27.77
|
12.749 ng/mL
Interval 5.79 to 25.44
|
16.440 ng/mL
Interval 10.71 to 32.84
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Maximum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile
Overall, Injection 1
|
32.235 ng/mL
Interval 19.53 to 55.89
|
16.878 ng/mL
Interval 9.35 to 57.61
|
22.825 ng/mL
Interval 10.89 to 41.14
|
|
Total Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile
Overall, Injection 3
|
38.300 ng/mL
Interval 23.76 to 53.45
|
17.885 ng/mL
Interval 8.56 to 42.11
|
30.804 ng/mL
Interval 16.64 to 55.63
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Minimum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile
Overall, Injection 3
|
11.938 ng/mL
Interval 6.56 to 14.2
|
5.028 ng/mL
Interval 1.79 to 11.64
|
10.534 ng/mL
Interval 3.85 to 14.8
|
|
Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile
Overall, Injection 1
|
9.159 ng/mL
Interval 3.28 to 15.23
|
4.867 ng/mL
Interval 1.88 to 13.54
|
5.642 ng/mL
Interval 2.63 to 20.31
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] The degree of fluctuation of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cavg, expressed as a percentage. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Percent Fluctuation Over the PK Profile
Overall, Injection 1
|
153.386 percentage of average concentration
Interval 64.6 to 179.59
|
151.211 percentage of average concentration
Interval 69.88 to 371.07
|
135.238 percentage of average concentration
Interval 71.94 to 217.01
|
|
Total Risperidone PK: Percent Fluctuation Over the PK Profile
Overall, Injection 3
|
114.008 percentage of average concentration
Interval 86.28 to 181.92
|
108.226 percentage of average concentration
Interval 59.48 to 185.63
|
102.396 percentage of average concentration
Interval 57.34 to 162.19
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] The swing of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cmin. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Swing Over the PK Profile
Overall, Injection 3
|
2.019 ratio
Interval 1.47 to 6.07
|
2.588 ratio
Interval 0.9 to 7.48
|
2.052 ratio
Interval 0.74 to 4.29
|
|
Total Risperidone PK: Swing Over the PK Profile
Overall, Injection 1
|
2.928 ratio
Interval 0.98 to 8.4
|
2.502 ratio
Interval 1.02 to 12.44
|
2.150 ratio
Interval 1.03 to 5.39
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile
Overall, Injection 1
|
192.000 hours
Interval 6.0 to 574.3
|
168.000 hours
Interval 4.0 to 504.0
|
215.833 hours
Interval 4.0 to 579.02
|
|
Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile
Overall, Injection 3
|
216.000 hours
Interval 168.0 to 504.18
|
216.00 hours
Interval 12.0 to 408.0
|
264.067 hours
Interval 24.0 to 408.0
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Accumulation index in terms of AUC calculated as ratio of AUCtau injection 3 / injection 1. Tau = 28 days. The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=10 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=14 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=14 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC))
|
1.2 ratio
Interval 1.0 to 1.7
|
1.1 ratio
Interval 0.8 to 2.9
|
1.6 ratio
Interval 1.0 to 2.9
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Accumulation index in terms of Cmax calculated as ratio of Cmax injection 3 / injection 1. The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=10 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=14 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax))
|
1.105 ratio
Interval 0.81 to 2.19
|
0.976 ratio
Interval 0.62 to 2.21
|
1.525 ratio
Interval 0.73 to 2.83
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Area under plasma concentration-time curve from 24 hours (Day 2) to the last quantifiable collection during dosing interval (28 days); calculated using the linear trapezoidal rule. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 at time of study drug administration.
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29)
Secondary Peak, Injection 1
|
10001.4 hr*ng/mL
Interval 5973.7 to 16936.7
|
6186.9 hr*ng/mL
Interval 2219.4 to 16241.8
|
7735.1 hr*ng/mL
Interval 3458.0 to 18517.4
|
|
Total Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29)
Secondary Peak, Injection 3
|
15484.3 hr*ng/mL
Interval 9954.0 to 17931.7
|
8236.4 hr*ng/mL
Interval 3726.5 to 16278.8
|
10988.6 hr*ng/mL
Interval 7047.1 to 21379.3
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] The average of plasma concentrations in the plateau, calculated as AUC Day 2-29/time Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29)
Secondary Peak, Injection 3
|
23.896 ng/mL
Interval 15.36 to 27.67
|
12.710 ng/mL
Interval 5.75 to 25.12
|
16.958 ng/mL
Interval 10.88 to 32.99
|
|
Total Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29)
Secondary Peak, Injection 1
|
15.434 ng/mL
Interval 9.22 to 26.14
|
9.548 ng/mL
Interval 3.42 to 25.06
|
11.937 ng/mL
Interval 5.34 to 28.58
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Maximum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: Secondary Peak, Injection 1 (Day 2 - Day 29) Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax)
Secondary Peak, Injection 1
|
32.235 ng/mL
Interval 19.53 to 55.89
|
16.867 ng/mL
Interval 6.42 to 57.61
|
21.415 ng/mL
Interval 9.26 to 41.06
|
|
Total Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax)
Secondary Peak, Injection 3
|
38.300 ng/mL
Interval 23.76 to 53.45
|
17.885 ng/mL
Interval 8.56 to 42.11
|
30.804 ng/mL
Interval 16.64 to 55.63
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Minimum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak
Secondary Peak, Injection 1
|
9.159 ng/mL
Interval 3.28 to 15.23
|
4.867 ng/mL
Interval 1.88 to 13.54
|
5.642 ng/mL
Interval 2.63 to 20.31
|
|
Total Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak
Secondary Peak, Injection 3
|
13.735 ng/mL
Interval 8.47 to 21.91
|
5.028 ng/mL
Interval 1.79 to 13.33
|
10.534 ng/mL
Interval 3.85 to 18.26
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] The degree of fluctuation of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cavg, expressed as a percentage. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Percent Fluctuation Over the Secondary Peak
Secondary Peak, Injection 1
|
151.294 percentage of average concentration
Interval 76.81 to 187.04
|
122.350 percentage of average concentration
Interval 70.17 to 246.65
|
122.042 percentage of average concentration
Interval 72.6 to 204.59
|
|
Total Risperidone PK: Percent Fluctuation Over the Secondary Peak
Secondary Peak, Injection 3
|
96.489 percentage of average concentration
Interval 80.33 to 162.36
|
101.788 percentage of average concentration
Interval 59.5 to 183.28
|
101.666 percentage of average concentration
Interval 55.92 to 162.53
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] The swing of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cmin. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Swing Over the Secondary Peak
Secondary Peak, Injection 3
|
1.679 ratio
Interval 1.15 to 5.17
|
2.412 ratio
Interval 0.9 to 7.48
|
1.914 ratio
Interval 0.72 to 3.91
|
|
Total Risperidone PK: Swing Over the Secondary Peak
Secondary Peak, Injection 1
|
2.928 ratio
Interval 0.98 to 5.26
|
2.048 ratio
Interval 1.02 to 12.44
|
2.017 ratio
Interval 1.02 to 5.39
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Total risperidone concentration (risperidone and 9-hydroxyrisperidone) was determined by adding risperidone concentration to risperidone-equivalent concentration (obtained from the 9-hydroxyrisperidone data). Total risperidone concentration was calculated using the molecular weights of 410 for risperidone and 426 for 9-hydroxyrisperidone: * \[Total Risperidone\] = \[Risperidone\] + (410/426) \* \[9-hydroxyrisperidone\] Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak
Secondary Peak, Injection 1
|
192.000 hours
Interval 24.0 to 574.3
|
168.000 hours
Interval 23.83 to 504.0
|
264.000 hours
Interval 24.0 to 579.02
|
|
Total Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak
Secondary Peak, Injection 3
|
216.000 hours
Interval 168.0 to 504.18
|
228.000 hours
Interval 23.83 to 408.0
|
264.067 hours
Interval 24.0 to 408.0
|
PRIMARY outcome
Timeframe: Day 1-2, Day 57-58Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
AUC0-24 calculated using the linear trapezoidal rule. Results are reported across two timeframes: * Initial Peak, Injection 1 (Day 1 injection to 24 hours after injection) * Initial Peak, Injection 3 (Day 57 injection to 24 hours after injection) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24)
Initial Peak, Injection 1
|
99.5 hr*ng/mL
Interval 46.9 to 329.4
|
103.8 hr*ng/mL
Interval 19.7 to 482.2
|
87.8 hr*ng/mL
Interval 30.0 to 367.9
|
|
Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24)
Initial Peak, Injection 3
|
127.0 hr*ng/mL
Interval 82.1 to 329.2
|
98.7 hr*ng/mL
Interval 35.1 to 557.9
|
107.1 hr*ng/mL
Interval 61.2 to 554.5
|
PRIMARY outcome
Timeframe: Day 1-2, Day 57-58Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Cmax determined directly from individual concentration-time data. Results are reported across two timeframes: * Initial Peak, Injection 1 (Day 1 injection to 24 hours after injection) * Initial Peak, Injection 3 (Day 57 injection to 24 hours after injection) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak
Initial Peak, Injection 1
|
6.470 ng/mL
Interval 2.8 to 15.3
|
6.280 ng/mL
Interval 1.32 to 25.7
|
5.460 ng/mL
Interval 1.75 to 16.8
|
|
Risperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak
Initial Peak, Injection 3
|
7.145 ng/mL
Interval 4.27 to 18.3
|
4.955 ng/mL
Interval 1.98 to 26.3
|
6.680 ng/mL
Interval 2.89 to 30.6
|
PRIMARY outcome
Timeframe: Day 1-2, Day 57-58Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Tmax determined directly from individual concentration-time data. Results are reported across two timeframes: * Initial Peak, Injection 1 (Day 1 injection to 24 hours after injection) * Initial Peak, Injection 3 (Day 57 injection to 24 hours after injection) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak
Initial Peak, Injection 1
|
4.000 hours
Interval 1.0 to 6.0
|
6.000 hours
Interval 3.0 to 23.83
|
6.000 hours
Interval 2.0 to 6.02
|
|
Risperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak
Initial Peak, Injection 3
|
4.483 hours
Interval 2.0 to 24.0
|
6.000 hours
Interval 2.0 to 24.0
|
6.000 hours
Interval 3.0 to 24.08
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
AUCtau calculated using the linear trapezoidal rule. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau)
Overall, Injection 1
|
3099.4 hr*ng/mL
Interval 1768.5 to 7202.0
|
1250.9 hr*ng/mL
Interval 403.7 to 8706.0
|
1663.4 hr*ng/mL
Interval 764.3 to 10010.9
|
|
Risperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau)
Overall, Injection 3
|
3621.2 hr*ng/mL
Interval 2084.2 to 7812.0
|
2144.6 hr*ng/mL
Interval 741.2 to 10490.3
|
2647.1 hr*ng/mL
Interval 1683.5 to 15384.8
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
The average of plasma concentrations calculated as AUCtau/ tau (tau = 28 days) Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile
Overall, Injection 1
|
4.612 ng/mL
Interval 2.63 to 10.72
|
1.861 ng/mL
Interval 0.6 to 12.96
|
2.475 ng/mL
Interval 1.14 to 14.9
|
|
Risperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile
Overall, Injection 3
|
5.389 ng/mL
Interval 3.1 to 11.62
|
3.191 ng/mL
Interval 1.1 to 15.61
|
3.939 ng/mL
Interval 2.51 to 22.89
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Maximum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile
Overall, Injection 1
|
9.270 ng/mL
Interval 4.27 to 18.5
|
6.280 ng/mL
Interval 1.32 to 37.4
|
7.520 ng/mL
Interval 2.01 to 24.4
|
|
Risperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile
Overall, Injection 3
|
12.125 ng/mL
Interval 5.0 to 21.5
|
5.720 ng/mL
Interval 2.0 to 26.3
|
7.490 ng/mL
Interval 4.23 to 38.4
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Minimum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile
Overall, Injection 1
|
1.720 ng/mL
Interval 0.59 to 6.48
|
0.829 ng/mL
Interval 0.25 to 4.81
|
1.060 ng/mL
Interval 0.42 to 9.44
|
|
Risperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile
Overall, Injection 3
|
2.415 ng/mL
Interval 1.24 to 4.83
|
1.230 ng/mL
Interval 0.39 to 4.24
|
2.100 ng/mL
Interval 0.85 to 12.3
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
The degree of fluctuation of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cavg, expressed as a percentage. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Percent Fluctuation Over the PK Profile
Overall, Injection 3
|
143.652 percentage of average concentration
Interval 93.11 to 206.7
|
147.252 percentage of average concentration
Interval 75.6 to 212.01
|
140.688 percentage of average concentration
Interval 55.32 to 343.98
|
|
Risperidone PK: Percent Fluctuation Over the PK Profile
Overall, Injection 1
|
173.609 percentage of average concentration
Interval 80.43 to 258.5
|
190.745 percentage of average concentration
Interval 97.9 to 914.27
|
215.048 percentage of average concentration
Interval 100.42 to 423.52
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
The swing of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cmin. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Swing Over the PK Profile
Overall, Injection 1
|
4.938 ratio
Interval 1.33 to 12.06
|
4.575 ratio
Interval 1.58 to 34.19
|
4.151 ratio
Interval 1.58 to 32.57
|
|
Risperidone PK: Swing Over the PK Profile
Overall, Injection 3
|
3.159 ratio
Interval 1.78 to 8.12
|
4.077 ratio
Interval 1.19 to 6.09
|
2.863 ratio
Interval 0.77 to 10.56
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile
Overall, Injection 1
|
192.000 hours
Interval 3.0 to 384.95
|
6.000 hours
Interval 4.0 to 408.28
|
168.000 hours
Interval 3.0 to 336.0
|
|
Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile
Overall, Injection 3
|
180.000 hours
Interval 72.0 to 504.18
|
18.000 hours
Interval 2.0 to 408.0
|
192.000 hours
Interval 3.0 to 671.75
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Accumulation index in terms of AUC calculated as ratio of AUCtau injection 3 / injection 1. Tau = 28 days. The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=10 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=14 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=14 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC))
|
1.1 ratio
Interval 1.0 to 1.9
|
1.1 ratio
Interval 0.6 to 4.8
|
1.7 ratio
Interval 1.0 to 3.2
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Accumulation index in terms of Cmax calculated as ratio of Cmax injection 3 / injection 1. The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=10 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=14 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax))
|
1.155 ratio
Interval 0.62 to 1.59
|
1.049 ratio
Interval 0.2 to 2.16
|
1.214 ratio
Interval 0.54 to 2.85
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Area under plasma concentration-time curve from 24 hours (Day 2) to the last quantifiable collection during dosing interval (28 days); calculated using the linear trapezoidal rule. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29)
Secondary Peak, Injection 1
|
2937.3 hr*ng/mL
Interval 1133.1 to 6919.4
|
1198.2 hr*ng/mL
Interval 384.0 to 8450.7
|
1544.9 hr*ng/mL
Interval 730.6 to 9645.4
|
|
Risperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29)
Secondary Peak, Injection 3
|
3476.6 hr*ng/mL
Interval 1996.8 to 7597.0
|
2204.6 hr*ng/mL
Interval 836.0 to 9933.4
|
2494.8 hr*ng/mL
Interval 1621.8 to 14833.4
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
The average of plasma concentrations in the plateau, calculated as AUC Day 2-29/time Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29)
Secondary Peak, Injection 1
|
4.533 ng/mL
Interval 1.75 to 10.68
|
1.849 ng/mL
Interval 0.59 to 13.04
|
2.384 ng/mL
Interval 1.13 to 14.88
|
|
Risperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29)
Secondary Peak, Injection 3
|
5.365 ng/mL
Interval 3.08 to 11.72
|
3.402 ng/mL
Interval 1.29 to 15.33
|
3.850 ng/mL
Interval 2.5 to 22.89
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Maximum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: Secondary Peak, Injection 1 (Day 2 - Day 29) Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax)
Secondary Peak, Injection 1
|
7.950 ng/mL
Interval 2.98 to 18.5
|
3.120 ng/mL
Interval 0.76 to 37.4
|
5.950 ng/mL
Interval 2.01 to 24.4
|
|
Risperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax)
Secondary Peak, Injection 3
|
12.125 ng/mL
Interval 5.09 to 21.5
|
5.220 ng/mL
Interval 1.46 to 25.5
|
7.010 ng/mL
Interval 4.23 to 38.4
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Minimum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak
Secondary Peak, Injection 1
|
1.720 ng/mL
Interval 0.59 to 6.48
|
0.829 ng/mL
Interval 0.25 to 4.81
|
1.070 ng/mL
Interval 0.56 to 9.44
|
|
Risperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak
Secondary Peak, Injection 3
|
2.415 ng/mL
Interval 1.24 to 8.54
|
1.230 ng/mL
Interval 0.39 to 5.31
|
2.100 ng/mL
Interval 0.85 to 12.3
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
The degree of fluctuation of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cavg, expressed as a percentage. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Percent Fluctuation Over the Secondary Peak
Secondary Peak, Injection 3
|
138.380 percentage of average concentration
Interval 93.02 to 207.62
|
136.691 percentage of average concentration
Interval 75.83 to 211.81
|
125.387 percentage of average concentration
Interval 55.36 to 345.51
|
|
Risperidone PK: Percent Fluctuation Over the Secondary Peak
Secondary Peak, Injection 1
|
141.030 percentage of average concentration
Interval 80.73 to 239.67
|
134.805 percentage of average concentration
Interval 53.99 to 288.36
|
134.898 percentage of average concentration
Interval 68.79 to 274.33
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
The swing of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cmin. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Swing Over the Secondary Peak
Secondary Peak, Injection 3
|
2.698 ratio
Interval 1.52 to 8.12
|
3.736 ratio
Interval 1.09 to 6.09
|
2.652 ratio
Interval 0.77 to 10.56
|
|
Risperidone PK: Swing Over the Secondary Peak
Secondary Peak, Injection 1
|
3.813 ratio
Interval 1.33 to 6.77
|
2.644 ratio
Interval 0.74 to 16.05
|
2.680 ratio
Interval 0.94 to 8.52
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak
Secondary Peak, Injection 1
|
192.000 hours
Interval 24.0 to 385.83
|
120.000 hours
Interval 23.83 to 408.28
|
216.000 hours
Interval 24.02 to 336.0
|
|
Risperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak
Secondary Peak, Injection 3
|
180.000 hours
Interval 72.0 to 504.18
|
204.000 hours
Interval 23.83 to 576.0
|
216.00 hours
Interval 24.0 to 671.75
|
PRIMARY outcome
Timeframe: Day 1-2, Day 57-58Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
AUC0-24 calculated using the linear trapezoidal rule. Results are reported across two timeframes: * Initial Peak, Injection 1 (Day 1 injection to 24 hours after injection) * Initial Peak, Injection 3 (Day 57 injection to 24 hours after injection) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24)
Initial Peak, Injection 1
|
404.8 hr*ng/mL
Interval 152.4 to 715.0
|
237.0 hr*ng/mL
Interval 149.4 to 407.6
|
251.1 hr*ng/mL
Interval 84.4 to 855.4
|
|
9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24)
Initial Peak, Injection 3
|
342.6 hr*ng/mL
Interval 231.4 to 477.0
|
169.2 hr*ng/mL
Interval 76.6 to 291.0
|
263.4 hr*ng/mL
Interval 93.7 to 514.4
|
PRIMARY outcome
Timeframe: Day 1-2, Day 57-58Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Cmax determined directly from individual concentration-time data. Results are reported across two timeframes: * Initial Peak, Injection 1 (Day 1 injection to 24 hours after injection) * Initial Peak, Injection 3 (Day 57 injection to 24 hours after injection) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak
Initial Peak, Injection 3
|
17.450 ng/mL
Interval 10.6 to 27.4
|
9.470 ng/mL
Interval 4.64 to 15.1
|
12.900 ng/mL
Interval 4.73 to 27.1
|
|
9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) During Initial Peak
Initial Peak, Injection 1
|
17.500 ng/mL
Interval 7.32 to 33.3
|
11.100 ng/mL
Interval 6.64 to 24.3
|
12.900 ng/mL
Interval 4.17 to 37.8
|
PRIMARY outcome
Timeframe: Day 1-2, Day 57-58Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Tmax determined directly from individual concentration-time data. Results are reported across two timeframes: * Initial Peak, Injection 1 (Day 1 injection to 24 hours after injection) * Initial Peak, Injection 3 (Day 57 injection to 24 hours after injection) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak
Initial Peak, Injection 1
|
6.000 hours
Interval 0.0 to 24.0
|
4.000 hours
Interval 0.0 to 24.0
|
6.000 hours
Interval 0.0 to 24.02
|
|
9-hydroxyrisperidone PK: Time of Maximum Plasma Concentration (Tmax) During Initial Peak
Initial Peak, Injection 3
|
24.000 hours
Interval 23.85 to 24.0
|
24.000 hours
Interval 0.0 to 24.0
|
24.000 hours
Interval 23.83 to 24.08
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
AUCtau calculated using the linear trapezoidal rule. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau)
Overall, Injection 1
|
9862.2 hr*ng/mL
Interval 6172.8 to 12526.6
|
4927.0 hr*ng/mL
Interval 2074.5 to 8428.4
|
5607.5 hr*ng/mL
Interval 1788.4 to 18485.5
|
|
9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (Where Tau=28 Days) (AUCtau)
Overall, Injection 3
|
11666.9 hr*ng/mL
Interval 8212.3 to 14354.6
|
5538.3 hr*ng/mL
Interval 2877.4 to 11191.6
|
8546.7 hr*ng/mL
Interval 3039.2 to 14534.1
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
The average of plasma concentrations calculated as AUCtau/ tau (tau = 28 days) Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile
Overall, Injection 1
|
14.676 ng/mL
Interval 9.19 to 18.64
|
7.332 ng/mL
Interval 3.09 to 12.54
|
8.344 ng/mL
Interval 2.66 to 27.51
|
|
9-hydroxyrisperidone PK: Average Plasma Concentration (Cavg) Over the PK Profile
Overall, Injection 3
|
17.361 ng/mL
Interval 12.22 to 21.36
|
8.242 ng/mL
Interval 4.28 to 16.65
|
12.718 ng/mL
Interval 4.52 to 21.63
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Maximum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile
Overall, Injection 1
|
22.400 ng/mL
Interval 15.6 to 40.2
|
12.300 ng/mL
Interval 8.48 to 24.3
|
15.600 ng/mL
Interval 4.17 to 39.2
|
|
9-hydroxyrisperidone PK: Maximum Plasma Concentration (Cmax) Over the PK Profile
Overall, Injection 3
|
29.600 ng/mL
Interval 19.4 to 37.8
|
13.450 ng/mL
Interval 6.34 to 32.4
|
21.200 ng/mL
Interval 7.3 to 34.7
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Minimum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile
Overall, Injection 1
|
6.690 ng/mL
Interval 2.75 to 11.4
|
3.940 ng/mL
Interval 1.4 to 9.28
|
4.240 ng/mL
Interval 2.14 to 19.1
|
|
9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the PK Profile
Overall, Injection 3
|
8.365 ng/mL
Interval 3.6 to 12.5
|
4.180 ng/mL
Interval 1.29 to 8.11
|
6.580 ng/mL
Interval 2.41 to 11.6
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
The degree of fluctuation of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cavg, expressed as a percentage. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Percent Fluctuation Over the PK Profile
Overall, Injection 3
|
122.701 percentage of average concentration
Interval 79.58 to 172.77
|
121.077 percentage of average concentration
Interval 47.08 to 195.1
|
106.728 percentage of average concentration
Interval 80.34 to 174.9
|
|
9-hydroxyrisperidone PK: Percent Fluctuation Over the PK Profile
Overall, Injection 1
|
142.828 percentage of average concentration
Interval 66.46 to 178.05
|
120.024 percentage of average concentration
Interval 66.15 to 313.0
|
124.696 percentage of average concentration
Interval 73.07 to 193.81
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
The swing of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cmin. Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Swing Over the PK Profile
Overall, Injection 1
|
2.633 ratio
Interval 0.96 to 8.37
|
1.984 ratio
Interval 0.99 to 12.11
|
2.041 ratio
Interval 0.89 to 5.72
|
|
9-hydroxyrisperidone PK: Swing Over the PK Profile
Overall, Injection 3
|
2.240 ratio
Interval 1.36 to 7.97
|
2.901 ratio
Interval 0.63 to 8.24
|
2.142 ratio
Interval 1.28 to 6.51
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Results are reported across two timeframes: * Overall, Injection 1 (Day 1 injection to Day 28) * Overall, Injection 3 (Day 57 injection to Day 84) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile
Overall, Injection 1
|
192.000 hours
Interval 0.0 to 574.3
|
168.000 hours
Interval 0.0 to 504.0
|
168.000 hours
Interval 0.0 to 579.02
|
|
9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the PK Profile
Overall, Injection 3
|
216.000 hours
Interval 168.0 to 552.0
|
216.000 hours
Interval 1.0 to 408.0
|
264.000 hours
Interval 24.0 to 336.0
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Accumulation index in terms of AUC calculated as ratio of AUCtau injection 3 / injection 1. Tau = 28 days. The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=10 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=14 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=14 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Area Under the Plasma Concentration Curve (Rac(AUC))
|
1.2 ratio
Interval 1.0 to 1.8
|
1.1 ratio
Interval 0.8 to 2.1
|
1.5 ratio
Interval 1.0 to 2.8
|
PRIMARY outcome
Timeframe: Day 1-28, Day 57-84Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Accumulation index in terms of Cmax calculated as ratio of Cmax injection 3 / injection 1. The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=10 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=14 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Accumulation Index Between Injections 1 and 3 In Terms of Maximum Plasma Concentrations (Rac(Cmax))
|
1.076 ratio
Interval 0.89 to 2.42
|
0.997 ratio
Interval 0.51 to 2.2
|
1.442 ratio
Interval 0.74 to 2.51
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Area under plasma concentration-time curve from 24 hours (Day 2) to the last quantifiable collection during dosing interval (28 days); calculated using the linear trapezoidal rule. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29)
Secondary Peak, Injection 1
|
7891.0 hr*ng/mL
Interval 5039.4 to 12116.0
|
4696.8 hr*ng/mL
Interval 1906.9 to 8095.4
|
5222.9 hr*ng/mL
Interval 1704.6 to 17634.8
|
|
9-hydroxyrisperidone PK: Area Under the Plasma Concentration-Time Curve From Day 2-29 Post Injection (AUC Day 2-29)
Secondary Peak, Injection 3
|
11786.5 hr*ng/mL
Interval 7982.8 to 13933.7
|
5388.2 hr*ng/mL
Interval 2775.2 to 10973.2
|
8311.7 hr*ng/mL
Interval 2943.9 to 14239.6
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
The average of plasma concentrations in the plateau, calculated as AUC Day 2-29/time Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29)
Secondary Peak, Injection 1
|
12.177 ng/mL
Interval 7.78 to 18.7
|
7.248 ng/mL
Interval 2.94 to 12.49
|
8.060 ng/mL
Interval 2.63 to 27.21
|
|
9-hydroxyrisperidone PK: Average Plasma Concentration Over the Secondary Peak (Cavg, Day 2-29)
Secondary Peak, Injection 3
|
18.189 ng/mL
Interval 12.32 to 21.5
|
8.315 ng/mL
Interval 4.28 to 16.93
|
12.827 ng/mL
Interval 4.54 to 21.97
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Maximum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: Secondary Peak, Injection 1 (Day 2 - Day 29) Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax)
Secondary Peak, Injection 1
|
22.300 ng/mL
Interval 15.6 to 40.2
|
12.300 ng/mL
Interval 6.15 to 21.5
|
15.600 ng/mL
Interval 3.45 to 39.2
|
|
9-hydroxyrisperidone PK: Maximum Plasma Concentration Over the Secondary Peak (Cmax)
Secondary Peak, Injection 3
|
29.600 ng/mL
Interval 19.4 to 37.8
|
13.450 ng/mL
Interval 6.34 to 32.4
|
21.200 ng/mL
Interval 7.3 to 34.7
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Minimum plasma concentrations determined directly from individual concentration-time data. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak
Secondary Peak, Injection 1
|
7.060 ng/mL
Interval 2.75 to 11.4
|
3.940 ng/mL
Interval 1.4 to 9.28
|
4.250 ng/mL
Interval 2.14 to 19.1
|
|
9-hydroxyrisperidone PK: Minimum Plasma Concentration (Cmin) Over the Secondary Peak
Secondary Peak, Injection 3
|
11.450 ng/mL
Interval 6.76 to 12.0
|
4.180 ng/mL
Interval 1.45 to 8.11
|
7.660 ng/mL
Interval 2.41 to 13.6
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
The degree of fluctuation of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cavg, expressed as a percentage. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Percent Fluctuation Over the Secondary Peak
Secondary Peak, Injection 3
|
101.956 percentage of average concentration
Interval 79.06 to 147.98
|
106.055 percentage of average concentration
Interval 34.5 to 191.68
|
104.207 percentage of average concentration
Interval 58.02 to 139.5
|
|
9-hydroxyrisperidone PK: Percent Fluctuation Over the Secondary Peak
Secondary Peak, Injection 1
|
141.300 percentage of average concentration
Interval 73.92 to 210.24
|
112.945 percentage of average concentration
Interval 57.64 to 252.39
|
127.274 percentage of average concentration
Interval 47.14 to 183.19
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
The swing of total risperidone plasma concentrations calculated as (Cmax - Cmin) / Cmin. Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Swing Over the Secondary Peak
Secondary Peak, Injection 3
|
1.595 ratio
Interval 1.12 to 4.31
|
2.018 ratio
Interval 0.46 to 8.24
|
1.991 ratio
Interval 0.74 to 2.88
|
|
9-hydroxyrisperidone PK: Swing Over the Secondary Peak
Secondary Peak, Injection 1
|
2.633 ratio
Interval 0.96 to 5.95
|
1.936 ratio
Interval 0.77 to 12.11
|
2.041 ratio
Interval 0.56 to 4.54
|
PRIMARY outcome
Timeframe: Day 2-29, Day 58-85Population: The PK analysis population was defined as all participants who received an injection of RBP-7000 and had an adequate number of PK blood draws (as determined by a clinical pharmacologist/pharmacokineticist) in order to provide a meaningful analysis of PK parameters.
Results are reported across two timeframes: * Secondary Peak, Injection 1 (Day 2 - Day 29) * Secondary Peak, Injection 3 (Day 58 - Day 85) The PK sampling schedule was: * Days 1 and 57: within 15 minutes prior to dosing, and at 1, 2, 3, 4, 6, and 12 hours post-dose * Days 2, 4, 6, 8-12, 15, 18, 22, 25, 58, 60, 62, 64-68, 71, 74, 78, 81 once each day at same time of day as study drug administration
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak
Secondary Peak, Injection 1
|
216.000 hours
Interval 24.0 to 574.3
|
216.000 hours
Interval 24.0 to 504.0
|
168.000 hours
Interval 24.0 to 579.02
|
|
9-hydroxyrisperidone PK: Time of the Maximum Plasma Concentration (Tmax) Over the Secondary Peak
Secondary Peak, Injection 3
|
216.000 hours
Interval 168.0 to 552.0
|
228.000 hours
Interval 24.0 to 408.0
|
264.000 hours
Interval 24.0 to 336.0
|
SECONDARY outcome
Timeframe: Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)Population: Safety
The switch from oral risperidone to RBP-7000 subcutaneous injections for efficacy markers used the PANSS scores. The PANSS assessment is a medical scale designed to measure symptom severity among patients with schizophrenia. Each item is rated on a scale of 1=absent to 7=extreme. PANSS consists of three components: * The General Psychopathology Scale consists of 16 questions with a total range of 16 (no schizophrenia symptoms) to 112 (extreme schizophrenia symptoms). * Both the Positive Scale and the Negative Scale consists of 7 questions with a total range of 7 (no schizophrenia symptoms) to 49 (extreme symptoms) on each scale. The PANSS range for assuring stability was a total PANSS General Psychopathology Scale score of 70 or less, with no score of 4 on any of the 7 questions in the Positive scale.
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106
Day 28: General Psychopathology Scale
|
27.0 units on a scale
Interval 22.0 to 40.0
|
28.0 units on a scale
Interval 19.0 to 33.0
|
26.0 units on a scale
Interval 20.0 to 46.0
|
|
Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106
Day 28: Positive Scale
|
12.0 units on a scale
Interval 10.0 to 20.0
|
13.0 units on a scale
Interval 11.0 to 23.0
|
12.0 units on a scale
Interval 8.0 to 24.0
|
|
Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106
Day 28: Negative Scale
|
18.0 units on a scale
Interval 12.0 to 22.0
|
16.0 units on a scale
Interval 11.0 to 22.0
|
17.0 units on a scale
Interval 9.0 to 23.0
|
|
Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106
Day 56: General Psychopathology Scale
|
25.0 units on a scale
Interval 22.0 to 29.0
|
28.0 units on a scale
Interval 22.0 to 33.0
|
26.0 units on a scale
Interval 20.0 to 34.0
|
|
Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106
Day 56: Positive Scale
|
11.5 units on a scale
Interval 10.0 to 14.0
|
13.0 units on a scale
Interval 9.0 to 22.0
|
13.0 units on a scale
Interval 9.0 to 21.0
|
|
Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106
Day 56: Negative Scale
|
17.5 units on a scale
Interval 12.0 to 21.0
|
17.0 units on a scale
Interval 11.0 to 21.0
|
18.0 units on a scale
Interval 8.0 to 25.0
|
|
Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106
Day 84: General Psychopathology Scale
|
25.0 units on a scale
Interval 22.0 to 29.0
|
28.0 units on a scale
Interval 20.0 to 34.0
|
25.0 units on a scale
Interval 19.0 to 32.0
|
|
Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106
Day 84: Positive Scale
|
12.5 units on a scale
Interval 10.0 to 15.0
|
13.5 units on a scale
Interval 9.0 to 19.0
|
12.5 units on a scale
Interval 8.0 to 18.0
|
|
Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106
Day 84: Negative Scale
|
16.0 units on a scale
Interval 12.0 to 24.0
|
15.5 units on a scale
Interval 11.0 to 21.0
|
17.5 units on a scale
Interval 13.0 to 24.0
|
|
Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106
Day 106: General Psychopathology Scale
|
26.5 units on a scale
Interval 21.0 to 48.0
|
26.0 units on a scale
Interval 19.0 to 32.0
|
23.5 units on a scale
Interval 19.0 to 34.0
|
|
Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106
Day 106: Positive Scale
|
14.0 units on a scale
Interval 10.0 to 28.0
|
13.0 units on a scale
Interval 10.0 to 18.0
|
12.0 units on a scale
Interval 7.0 to 19.0
|
|
Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106
Day 106: Negative Scale
|
18.0 units on a scale
Interval 11.0 to 26.0
|
14.0 units on a scale
Interval 11.0 to 21.0
|
18.0 units on a scale
Interval 13.0 to 23.0
|
|
Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106
Baseline: General Psychopathology Scale
|
27.0 units on a scale
Interval 22.0 to 32.0
|
27.0 units on a scale
Interval 21.0 to 34.0
|
24.0 units on a scale
Interval 21.0 to 32.0
|
|
Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106
Baseline: Positive Scale
|
13.0 units on a scale
Interval 10.0 to 17.0
|
13.0 units on a scale
Interval 10.0 to 15.0
|
14.0 units on a scale
Interval 8.0 to 17.0
|
|
Positive and Negative Syndrome Scale (PANSS) Scores at Baseline and Days 28, 56, 84 and 106
Baseline: Negative Scale
|
18.0 units on a scale
Interval 13.0 to 22.0
|
15.0 units on a scale
Interval 11.0 to 24.0
|
18.0 units on a scale
Interval 9.0 to 23.0
|
SECONDARY outcome
Timeframe: Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)Population: Safety
The switch from oral risperidone to RBP-7000 subcutaneous injections for efficacy markers used CGI scores. The CGI is used in the assessment of global illness severity and change in clinical condition over time in psychiatric patients. Severity of illness is measured on a 7-point scale with 1=normal, not at all ill and 7=among the most extremely ill patients. Global improvement is measured on a 7-point scale with 1=very much improved, 4=no change and 7=very much worse as compared to the severity of illness at baseline.
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106
Baseline: Severity of illness
|
3.0 units on a scale
Interval 3.0 to 3.0
|
3.0 units on a scale
Interval 3.0 to 3.0
|
3.0 units on a scale
Interval 3.0 to 3.0
|
|
Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106
Day 28: Severity of illness
|
3.0 units on a scale
Interval 3.0 to 4.0
|
3.0 units on a scale
Interval 3.0 to 3.0
|
3.0 units on a scale
Interval 3.0 to 4.0
|
|
Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106
Day 28: Global improvement
|
4.0 units on a scale
Interval 3.0 to 5.0
|
4.0 units on a scale
Interval 3.0 to 5.0
|
4.0 units on a scale
Interval 3.0 to 6.0
|
|
Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106
Day 56: Severity of illness
|
3.0 units on a scale
Interval 3.0 to 3.0
|
3.0 units on a scale
Interval 3.0 to 3.0
|
3.0 units on a scale
Interval 3.0 to 4.0
|
|
Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106
Day 56: Global improvement
|
4.0 units on a scale
Interval 4.0 to 4.0
|
4.0 units on a scale
Interval 4.0 to 5.0
|
4.0 units on a scale
Interval 4.0 to 5.0
|
|
Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106
Day 84: Severity of illness
|
3.0 units on a scale
Interval 3.0 to 3.0
|
3.0 units on a scale
Interval 3.0 to 3.0
|
3.0 units on a scale
Interval 3.0 to 3.0
|
|
Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106
Day 84: Global improvement
|
4.0 units on a scale
Interval 4.0 to 4.0
|
4.0 units on a scale
Interval 3.0 to 4.0
|
4.0 units on a scale
Interval 3.0 to 5.0
|
|
Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106
Day 106: Severity of illness
|
3.0 units on a scale
Interval 3.0 to 5.0
|
3.0 units on a scale
Interval 3.0 to 3.0
|
3.0 units on a scale
Interval 3.0 to 3.0
|
|
Clinical Global Impression (CGI) Scores (Severity of Illness and Global Improvement) at Baseline and Days 28, 56, 84 and 106
Day 106: Global improvement
|
4.0 units on a scale
Interval 3.0 to 6.0
|
4.0 units on a scale
Interval 2.0 to 4.0
|
4.0 units on a scale
Interval 3.0 to 5.0
|
SECONDARY outcome
Timeframe: Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)Population: Safety
The switch from oral risperidone to RBP-7000 subcutaneous injections for safety markers used AIMS. The AIMS is a scale that aids in the early detection and ongoing monitoring of tardive dyskinesia, a movement disorder that can result from long-term treatment with antipsychotic medication. By assessing the participant's body movement in specific positions requiring rotation, a psychiatrist is able to determine whether abnormal facial or body movements exist. The total score is the sum of 7 questions assessing movement plus 3 questions representing global assessments on the overall level of involuntary movement severity, incapacitation due to involuntary movement, and patient's awareness of involuntary movement. Each of the 10 questions are scored on a 0 (none) - 4 (extremely severe) scale. Plus two dental status questions are scored on a 0 (no) - 1 (yes) scale. The total score is therefore a scale of 0 (normal) - 42 (advanced tardive dyskinesia).
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106
Baseline
|
1.0 units on a scale
Interval 0.0 to 5.0
|
1.0 units on a scale
Interval 0.0 to 12.0
|
0.0 units on a scale
Interval 0.0 to 2.0
|
|
Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106
Day 28
|
1.0 units on a scale
Interval 0.0 to 6.0
|
1.0 units on a scale
Interval 0.0 to 12.0
|
0.0 units on a scale
Interval 0.0 to 4.0
|
|
Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106
Day 56
|
1.0 units on a scale
Interval 0.0 to 6.0
|
1.0 units on a scale
Interval 0.0 to 12.0
|
0.0 units on a scale
Interval 0.0 to 2.0
|
|
Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106
Day 84
|
1.0 units on a scale
Interval 0.0 to 5.0
|
0.5 units on a scale
Interval 0.0 to 12.0
|
0.0 units on a scale
Interval 0.0 to 4.0
|
|
Global Assessment of the Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia at Baseline and Days 28, 56, 84 and 106
Day 106
|
0.5 units on a scale
Interval 0.0 to 5.0
|
1.0 units on a scale
Interval 0.0 to 12.0
|
0.0 units on a scale
Interval 0.0 to 5.0
|
SECONDARY outcome
Timeframe: Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)Population: Safety
The switch from oral risperidone to RBP-7000 subcutaneous injections for safety markers used SAS. The SAS is a 10-item scale used to detect the presence of drug induced parkinsonism and extrapyramidal side effects, and evaluates symptom severity. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0 to 4 scale with 0=normal and 4=extreme description of the particular side effect. The total range is 0=no side effects observed to 40 = extreme of each of the 10 side effects.
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106
Baseline
|
0.0 units on a scale
Interval 0.0 to 2.0
|
0.0 units on a scale
Interval 0.0 to 0.0
|
0.0 units on a scale
Interval 0.0 to 0.0
|
|
Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106
Day 28
|
0.0 units on a scale
Interval 0.0 to 1.0
|
0.0 units on a scale
Interval 0.0 to 0.0
|
0.0 units on a scale
Interval 0.0 to 3.0
|
|
Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106
Day 56
|
0.0 units on a scale
Interval 0.0 to 1.0
|
0.0 units on a scale
Interval 0.0 to 0.0
|
0.0 units on a scale
Interval 0.0 to 0.0
|
|
Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106
Day 84
|
0.0 units on a scale
Interval 0.0 to 1.0
|
0.0 units on a scale
Interval 0.0 to 0.0
|
0.0 units on a scale
Interval 0.0 to 0.0
|
|
Total Simpson-Angus Scale (SAS) Score at Baseline and Days 28, 56, 84 and 106
Day 106
|
0.0 units on a scale
Interval 0.0 to 1.0
|
0.0 units on a scale
Interval 0.0 to 0.0
|
0.0 units on a scale
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)Population: Safety
The BAS is a scale that detects the presence and severity of any drug induced akathisia. The scale measures objective and subjective effects such as restlessness and awareness of restlessness, respectively. Participants are observed while seated, then while standing and engaged in neutral conversation. Symptoms observed during additional situations, such as participant behavior on the ward, may also be rated. Subjective phenomena should be elicited through direct questioning of the participant. The global clinical assessment is reported on a scale of 0 to 5, where 0 = absent and 5 = severe akathisia.
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106
Baseline
|
0.0 units on a scale
Interval 0.0 to 1.0
|
0.0 units on a scale
Interval 0.0 to 2.0
|
0.0 units on a scale
Interval 0.0 to 0.0
|
|
Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106
Day 28
|
0.0 units on a scale
Interval 0.0 to 0.0
|
0.0 units on a scale
Interval 0.0 to 2.0
|
0.0 units on a scale
Interval 0.0 to 1.0
|
|
Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106
Day 56
|
0.0 units on a scale
Interval 0.0 to 0.0
|
0.0 units on a scale
Interval 0.0 to 2.0
|
0.0 units on a scale
Interval 0.0 to 0.0
|
|
Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106
Day 84
|
0.0 units on a scale
Interval 0.0 to 0.0
|
0.0 units on a scale
Interval 0.0 to 2.0
|
0.0 units on a scale
Interval 0.0 to 0.0
|
|
Global Clinical Assessment of Akathisia Using the Barnes Akathisia Scale (BAS) at Baseline and Days 28, 56, 84 and 106
Day 106
|
0.0 units on a scale
Interval 0.0 to 1.0
|
0.0 units on a scale
Interval 0.0 to 2.0
|
0.0 units on a scale
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline (Day -1), Days 28, 56, 84, and End of Study (Day 106 or early termination visit)Population: Safety
The C-SSRS is a scale developed by the National Institute of Mental Health trial group as a counterpart to the FDA's categorization of suicidal events. It was developed by a careful review and consequent categorization of thoughts and behavior that were statistically identified as significantly related to suicidal behavior. The scale captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors throughout lifetime at screening, baseline, and for the time interval since last administration for repeat administrations during a study. This outcome reports the number of participants with suicidal ideation or behavior.
Outcome measures
| Measure |
Cohort 3, RBP-7000 120 mg
n=15 Participants
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
Cohort 1, RBP-7000 60 mg
n=15 Participants
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 Participants
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
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
Baseline: Suicidal ideation or behavior
|
0 Participants
|
0 Participants
|
0 Participants
|
|
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
Day 28: Suicidal ideation or behavior
|
1 Participants
|
0 Participants
|
1 Participants
|
|
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
Day 56: Suicidal ideation or behavior
|
0 Participants
|
1 Participants
|
0 Participants
|
|
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
Day 84: Suicidal ideation or behavior
|
0 Participants
|
0 Participants
|
0 Participants
|
|
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
Day 106: Suicidal ideation or behavior
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Cohort 1, RBP-7000 60 mg
Cohort 2, RBP-7000 90 mg
Cohort 3, RBP-7000 120 mg
Serious adverse events
| Measure |
Cohort 1, RBP-7000 60 mg
n=15 participants at risk
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 participants at risk
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
Cohort 3, RBP-7000 120 mg
n=15 participants at risk
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
Other adverse events
| Measure |
Cohort 1, RBP-7000 60 mg
n=15 participants at risk
Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.
|
Cohort 2, RBP-7000 90 mg
n=15 participants at risk
Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.
|
Cohort 3, RBP-7000 120 mg
n=15 participants at risk
Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.
|
|---|---|---|---|
|
Ear and labyrinth disorders
Otorrhoea
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Gastrointestinal disorders
Dyspepsia
|
6.7%
1/15 • Day 1 to Day 106
|
13.3%
2/15 • Day 1 to Day 106
|
20.0%
3/15 • Day 1 to Day 106
|
|
Gastrointestinal disorders
Abdominal pain upper
|
13.3%
2/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Gastrointestinal disorders
Toothache
|
13.3%
2/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
|
General disorders
Fatigue
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
General disorders
Influenza-like illness
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Infections and infestations
Nasopharyngitis
|
6.7%
1/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
|
Infections and infestations
Cellulitis
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Infections and infestations
Gastroenteritis viral
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Infections and infestations
Tooth infection
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Infections and infestations
Upper respiratory tract infection
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Infections and infestations
Urethritis
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Injury, poisoning and procedural complications
Excoriation
|
13.3%
2/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
|
Investigations
Weight increased
|
26.7%
4/15 • Day 1 to Day 106
|
33.3%
5/15 • Day 1 to Day 106
|
20.0%
3/15 • Day 1 to Day 106
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.7%
1/15 • Day 1 to Day 106
|
13.3%
2/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.7%
1/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
13.3%
2/15 • Day 1 to Day 106
|
|
Nervous system disorders
Headache
|
20.0%
3/15 • Day 1 to Day 106
|
20.0%
3/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
|
Nervous system disorders
Extrapyramidal disorder
|
13.3%
2/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
|
Nervous system disorders
Somnolence
|
6.7%
1/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
|
Nervous system disorders
Drooling
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
|
Nervous system disorders
Akathisia
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Nervous system disorders
Dizziness
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Nervous system disorders
Tremor
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Psychiatric disorders
Anxiety
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Psychiatric disorders
Depression
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
|
Renal and urinary disorders
Pyuria
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
|
Reproductive system and breast disorders
Sexual dysfunction
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
20.0%
3/15 • Day 1 to Day 106
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Skin and subcutaneous tissue disorders
Rash
|
20.0%
3/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Skin and subcutaneous tissue disorders
Dermititis contact
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
|
Skin and subcutaneous tissue disorders
Seborrhoeic dermatitis
|
0.00%
0/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
|
Vascular disorders
Hot flush
|
0.00%
0/15 • Day 1 to Day 106
|
6.7%
1/15 • Day 1 to Day 106
|
0.00%
0/15 • Day 1 to Day 106
|
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