Long Term Study of RBP 7000 in the Treatment of Subjects With Schizophrenia

• Sponsor: Indivior Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02203838
• Collaborator: (none)
• Enrollment: 500
• Locations: 48
• Arm: 1
• Duration (Months): 27
• Patients Per Site: 10.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a Phase 3, open label study administering RBP-7000 in the treatment of patients with schizophrenia. Study will assess the long-term safety and tolerability of RBP-7000 subcutaneous (SC) injections in subjects with schizophrenia and to continue collecting clinical outcome data with RBP-7000 SC injections in subjects with schizophrenia using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity Illness (CGI-S) scale.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: RBP-7000	Phase 3

Detailed Description

Patients to be screened must be diagnosed with schizophrenia with a designated score based on the PANSS, as confirmed by a State, Assessability, Face, Ecological and Rule (SAFER) interview. "De novo" patients are patients who are already receiving 3- or 4-mg oral risperidone/day and will not have to complete the "run-in" or "conversion" phases (see below) and will be assigned to receive RBP-7000 after eligibility has been confirmed. Patients who completed the double-blind, placebo-controlled, efficacy study of RBP-7000 (RB-US-09-0010, NCT02109562), conducted in patients with acute schizophrenia (referred to as "roll-over" patients) will be screened.

All patients will be assigned the 120 mg dose of RBP-7000, which is subject to a one-time down-titration to 90-mg RBP-7000 for tolerability, at the investigator's discretion. Patients receiving the 90-mg dose of RBP-7000 who exhibit a worsening in psychiatric symptoms, confirmed by a total PANSS score >70 or a 20% increase in the PANSS score from the previous assessment at the 120-mg dose level (before the dose was decreased to 90 mg), can receive a one-time, up-titration back to 120-mg RBP-7000 at the discretion of the investigator.

"De novo" patients entering into the study are those patients who did not participate in study RB-US-09-0010 (NCT02109562) and are allocated into three groups with different pre-study procedures to prepare for the treatment period:

• "Run-in" patients are patients who are not already receiving oral risperidone (as no other antipsychotic medications are allowed during study participation) and will begin a 14-day run-in period by titrating up to a dose of 3 or 4 mg oral risperidone/day before the first injection of RBP-7000.

• "Conversion" patients are patients who are receiving oral risperidone doses other than 3 or 4mg/day and will begin a 7-day conversion period to achieve an oral risperidone dose level of 3 or 4-mg before the first injection of RBP-7000, only if clinically indicated.

• De novo patients taking an oral risperidone dose of 3 or 4 mg/day prestudy will (once screened/enrolled) receive the first injection of RBP-7000.

"Roll-over" patients entering into the study are patients who completed 56 days of double-blind treatment in Study RB-US-09-0010. These patients will be eligible to enter the current study provided that continuation of treatment is clinically warranted, as judged by the investigator, and that there have been no significant protocol deviations or clinically relevant adverse events (AEs) that would preclude inclusion in this study. Roll-over patients will not undergo the complete screening process and will not require either a run-in or conversion period with oral risperidone. On Day 1 of the open-label study (which is Day 57 of Study RB-US-09-0010), patients will receive their first injection (120 mg) of open label RBP-7000.

Study Design

• Study Type: Interventional
• Actual Enrollment: 500 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Long-Term Safety and Tolerability Study of RBP-7000 in the Treatment of Subjects With Schizophrenia
• Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: Sep 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: RBP-7000 - 120-mg dose RBP-7000 120-mg subcutaneous (SC) injections every 28 days for 13 doses as open-label therapy. Patients enter the study as 'roll-over' patients from study RB-US-09-0010, or de novo patients. Pre-study procedures vary for de novo patients depending on previous therapy.

Drug: RBP-7000; 120-mg RBP-7000 dose delivered by subcutaneous injection every 28 days for a total of 13 injections (for roll-over participants, the first two injections took place under study RB-US-09-0010). A one-time down-titration to 90 mg RBP-7000 is permitted at the investigator's discretion should the participant have tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator. RBP-7000 is a combination of the ATRIGEL Delivery System and risperidone. The ATRIGEL Delivery System allows for sustained-release of risperidone in a controlled manner.; Other Names: Risperidone Long-acting Risperidone

Outcome Measures

Primary Outcome Measures

1. Participants With Treatment-Emergent Adverse Events (TEAE) [Day 1 up to week 52]

   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.

2. Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) [Day 1 up to week 52]

   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. Adverse events were coded using MedDRA version 17.0. Preferred terms linked to injection site AEs are reported. Although a participant may have had 2 or more AEs, the subject is counted only once in each preferred term category. The same subject may appear in different preferred term categories.

3. Participants With Markedly Abnormal Weight Gain Anytime During the Study as Compared to Baseline [Baseline (Day 0), Treatment (Day 1 up to Week 52)]

   Participants who were found to have gain >=7% and >=10% of their baseline weight at any point during the study (including unscheduled assessments) once treatment began.

Secondary Outcome Measures

1. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score to Days 29, 169 and End of Study [Baseline (Day 0), Day 29, Day 169 and End of Study (approximately Week 52)]

   The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor judgement, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score is the sum of all 30 PANSS items and ranges from 30 to 210, with 30 indicating absence of symptoms of schizophrenia and 210 indicating extreme ratings of all 30 symptoms. Negative change from baseline scores indicate improvements in symptoms.

2. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores to End of Study [Baseline (Day 0), End of Study (approximately Week 52)]

   PANSS subscales: Positive scale assesses 7 items: delusions, conceptual disorganization, hallucinations, excitement, grandiosity, suspiciousness/persecution, and hostility. Scale: 7 (absent) to 49 (extreme psychopathology) Negative scale assesses 7 items: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking. Scale: 7 (absent) to 49 (extreme psychopathology) General Psychopathology scale assesses 16 items: somatic concern, anxiety, guilt feelings, tension, mannerisms and posturing, depression, motor retardation, uncooperativeness, unusual thought content, disorientation, poor attention, lack of judgment and insight, disturbance of volition, poor impulse control, preoccupation, and active social avoidance. Scale: 16 (absent) to 112 (extreme psychopathology) Negative change from baseline scores indicate improvements.

3. Change From Baseline in Clinical Global Impression - Severity Scores (CGI-S) to Days 29, 169 and End of Study [Baseline (Day 0), Baseline (Day 0), Day 29, Day 169 and End of Study (approximately Week 52)]

   The CGI-S rating scale is a 7-point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants". Negative change from baseline scores indicate improvement in the severity of illness.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

"De Novo" Patients

• Diagnosis of schizophrenia as defined by Diagnostic and Statistical Manual, Edition 4, text revision (DSM-IV-TR) criteria

• Total PANSS score <=70 at the time of screening (Visit 1)

• Otherwise healthy on the basis of physical examinatIon

• Provided written informed consent

"Roll-over Patients

• Provided written consent to participate in this study

• Be considered eligible to enroll based on End of Study (EOS) (Day 57 of Study RB-US-09-0010) assessments and the medical judgment of the investigator

Exclusion Criteria:

"De Novo" Patients

• Patients taking daily oral risperidone at a dose plus/minus 6 mg/day

• Patients taking any risperidone or 9-hydroxyrisperidone long-acting injectable formulation within 120 days of study screening (Visit 1)

• Patients who have received a long-acting injectable antipsychotic within 120 days of screening (Visit 1)

• Patients with evidence or history (in the past six months prior to screening) of a significant hepatic disorder that may either compromise patient safety or interfere with the safety and/or outcome evaluation of the study drug, including:

• Acute or chronic hepatitis, including but not limited to hepatitis B or C

• Total bilirubin greater than 1.5 times the upper limit of normal (ULN), or

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2 times ULN

• Patients with a history of drug-induced leukopenia

• Patients with other medical conditions including, but not limited to, history of heart attack (myocardial infarction) or brain injury (traumatic injury with loss of consciousness and/or cerebrovascular accident), and clinically significant low blood pressure or arrhythmias as interpreted by the primary investigator (PI) or medically qualified sub-investigator

• Patients with epilepsy or other seizure disorders, Parkinson's disease or dementia

"Roll-over" Patients

• Patients requiring an inpatient treatment setting at the end of Study RB-US-09-0010

• Patients with an unstable medical condition developed during Study RB-US-09-0010

• Women of childbearing potential who have a positive pregnancy test at screening (Visit 1), who are pregnant or breastfeeding, seeking pregnancy, or failing to use adequate contraceptive methods during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Woodland International Research Group, Inc.	Little Rock	Arkansas	United States	72211
2	Woodland Research Northwest, LLC	Springdale	Arkansas	United States	72764
3	Comprehensive Clinical Development	Cerritos	California	United States	90703
4	Synergy EPIC	Escondido	California	United States	92025
5	Behavioral Research Specialists	Glendale	California	United States	91206
6	Collaborative Neuroscience Network, LLC	Long Beach	California	United States	90806
7	Apostle Clinical Trials	Long Beach	California	United States	90813
8	Pacific Research Partners	Oakland	California	United States	94612
9	Excell Research	Oceanside	California	United States	92056
10	CNRI-Los Angeles	Pico Rivera	California	United States	90660
11	CNRI-San Diego	San Diego	California	United States	92102
12	Research Center for Clinical Studies	Norwalk	Connecticut	United States	06851
13	Comprehensive Clinical Development-Washington DC	Washington	District of Columbia	United States	20016
14	Florida Clinical Research Center	Bradenton	Florida	United States	34201
15	Innovative Clinical Research	Fort Lauderdale	Florida	United States	33308
16	Behavioral Clinical Reserach	Hollywood	Florida	United States	33021
17	Florida Clinical Research Center	Maitland	Florida	United States	32751
18	Premier Clinical Resarch Institute	Miami	Florida	United States	33122
19	Radiant Research	Atlanta	Georgia	United States	30328
20	iResearch Atlanta	Decatur	Georgia	United States	30030
21	Uptown Research Institute	Chicago	Illinois	United States	60640
22	Behavioral Health Hospital	Hoffman Estates	Illinois	United States	60169
23	Baber Research Group	Naperville	Illinois	United States	60563
24	Via Christi Research	Wichita	Kansas	United States	67214
25	Lake Charles Clinical Trials	Lake Charles	Louisiana	United States	70629
26	Centerpointe Hospital	Saint Charles	Missouri	United States	63304
27	St. Louis Clinical Trials	Saint Louis	Missouri	United States	63118
28	Altea Research Institute	Las Vegas	Nevada	United States	89102
29	CRI Lifetree - Marlton Unit	Marlton	New Jersey	United States	08053-3426
30	Behavioral Medical Research of Brooklyn	Brooklyn	New York	United States	11241
31	Neurobehavioral Research	Cedarhurst	New York	United States	11516
32	Comprehensive Clinical Development-Queens	Jamaica	New York	United States	11432
33	Finger Lakes Clinical Research	Rochester	New York	United States	14618
34	New Hope Clinical Research	Charlotte	North Carolina	United States	28204
35	Clinical Trials of America	Hickory	North Carolina	United States	28601
36	Insight Clinical Trials LLC	Shaker Heights	Ohio	United States	44122
37	Oklahoma Clinical Research Center	Oklahoma City	Oklahoma	United States	73112
38	Cutting Edge Research Group	Oklahoma City	Oklahoma	United States	73116
39	Keystone Clinical Studies	Norristown	Pennsylvania	United States	19403
40	CRI Lifetree - Philadelphia Unit	Philadelphia	Pennsylvania	United States	19139
41	Berks Center for ClinicalResearch	Reading	Pennsylvania	United States	19604
42	Research Strategies of Memphis	Memphis	Tennessee	United States	38119
43	FutureSearch Clinical Trials	Austin	Texas	United States	78731
44	Community Clinical Research, Inc.	Austin	Texas	United States	78754
45	FutureSearch Clinical Trials, L.P.	Dallas	Texas	United States	75231
46	Pillar Clinical Research	Dallas	Texas	United States	75243
47	Bayou City Research	Houston	Texas	United States	77007
48	Alliance Research Group	Richmond	Virginia	United States	23230

Sponsors and Collaborators

• Indivior Inc.

Investigators

• Study Director: Indivior Inc., Indivior Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Indivior Inc.
• ClinicalTrials.gov Identifier: NCT02203838
• Other Study ID Numbers: RB-US-13-0005
• First Posted: Jul 30, 2014
• Last Update Posted: Sep 28, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Indivior Inc.: Schizophrenia; Schizophrenic; Schizophrenias; Risperidone; Long-acting Risperidone; Atrigel; Subcutaneous
• Additional relevant MeSH terms: Schizophrenia; Risperidone

Study Results

Participant Flow

Pre-assignment Detail	A total of 820 subjects were screened for study participation at 53 sites in the US. Overall, 500 participants were included in the Safety Population: 92 rollover participants and 408 de novo participants.

Arm/Group Title	De Novo Participants	Rollover Placebo	Rollover RBP-7000 90 mg	Rollover RBP-7000 120 mg
Arm/Group Description	Participants who were not part of the previous double-blind study. Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart. A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg of RBP-7000 at the discretion of the investigator.	Participants who were randomized to the placebo arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart. A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the RBP-7000 90 mg arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study). A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the RBP-7000 120 mg arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study). A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.
Period Title: Overall Study
STARTED	408	28	31	33
COMPLETED	198	6	15	15
NOT COMPLETED	210	22	16	18

Baseline Characteristics

Arm/Group Title	De Novo Participants	Rollover Placebo	Rollover RBP-7000 90 mg	Rollover RBP-7000 120 mg	Total
Arm/Group Description	Participants who were not part of the previous double-blind study. Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart. A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the placebo arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart. A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the RBP-7000 90 mg arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study). A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the RBP-7000 120 mg arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study). A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Total of all reporting groups
Overall Participants	408	28	31	33	500
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.7 (10.51)	44.0 (7.33)	41.1 (9.64)	42.3 (10.04)	45.1 (10.34)
Age, Customized (Count of Participants)
20 years and under	2 0.5%	0 0%	0 0%	1 3%	3 0.6%
21 to 30 years	39 9.6%	1 3.6%	4 12.9%	5 15.2%	49 9.8%
31 to 40 years	81 19.9%	9 32.1%	10 32.3%	6 18.2%	106 21.2%
41 to 50 years	128 31.4%	12 42.9%	11 35.5%	12 36.4%	163 32.6%
51 to 55 years	85 20.8%	6 21.4%	5 16.1%	9 27.3%	105 21%
56 to 65 years	73 17.9%	0 0%	1 3.2%	0 0%	74 14.8%
Sex: Female, Male (Count of Participants)
Female	133 32.6%	9 32.1%	6 19.4%	13 39.4%	161 32.2%
Male	275 67.4%	19 67.9%	25 80.6%	20 60.6%	339 67.8%
Race/Ethnicity, Customized (Count of Participants)
White	109 26.7%	9 32.1%	9 29%	9 27.3%	136 27.2%
Black or African American	292 71.6%	18 64.3%	22 71%	22 66.7%	354 70.8%
Asian	3 0.7%	0 0%	0 0%	1 3%	4 0.8%
American Indian or Alaska Native	2 0.5%	0 0%	0 0%	0 0%	2 0.4%
Native Hawaiian or Other Pacific Islander	1 0.2%	1 3.6%	0 0%	1 3%	3 0.6%
Other	1 0.2%	0 0%	0 0%	0 0%	1 0.2%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	36 8.8%	4 14.3%	2 6.5%	2 6.1%	44 8.8%
Not Hispanic or Latino	371 90.9%	24 85.7%	29 93.5%	31 93.9%	455 91%
Unknown	1 0.2%	0 0%	0 0%	0 0%	1 0.2%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	92.80 (20.989)	99.33 (25.113)	96.72 (21.305)	94.65 (23.994)	93.53 (21.463)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	31.121 (7.104)	33.920 (8.551)	31.926 (7.104)	31.838 (8.341)	31.375 (7.284)
Waist-to-Hip Ratio (ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ratio]	0.946 (0.090)	0.936 (0.094)	0.975 (0.059)	0.935 (0.075)	0.946 (0.087)
Child-bearing Potential (Count of Participants)
Yes	54 13.2%	4 14.3%	3 9.7%	5 15.2%	66 13.2%
No	79 19.4%	5 17.9%	3 9.7%	8 24.2%	95 19%
Positive and Negative Syndrome Scale (PANSS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	58.0 (8.33)	72.9 (20.99)	76.4 (15.99)	71.0 (13.93)	60.9 (12.04)
Clinical Global Impression - Severity Scale (CGI-S) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	3.3 (0.62)	3.7 (1.09)	3.8 (0.95)	3.3 (0.89)	3.4 (0.71)

Outcome Measures

1. Primary Outcome

Title	Participants With Treatment-Emergent Adverse Events (TEAE)
Description	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.
Time Frame	Day 1 up to week 52

Outcome Measure Data

Analysis Population Description

Safety population -- participants who received at least 1 dose of study drug.

Arm/Group Title	De Novo Participants	Rollover Placebo	Rollover RBP-7000 90 mg	Rollover RBP-7000 120 mg
Arm/Group Description	Participants who were not part of the previous double-blind study. Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart. A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the placebo arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart. A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the RBP-7000 90 mg arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study). A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the RBP-7000 120 mg arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study). A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.
Measure Participants	408	28	31	33
1 or more TEAE	306 75%	21 75%	22 71%	18 54.5%
>=1 TEAE related to study drug	232 56.9%	12 42.9%	14 45.2%	12 36.4%
>=1 serious TEAE	25 6.1%	3 10.7%	3 9.7%	3 9.1%
>=1 serious and related TEAE	0 0%	0 0%	0 0%	0 0%
TEAE leading to dose modification	38 9.3%	2 7.1%	1 3.2%	2 6.1%
TEAE leading to discontinuation	47 11.5%	6 21.4%	3 9.7%	2 6.1%
TEAE leading to death	3 0.7%	1 3.6%	0 0%	0 0%

2. Primary Outcome

Title	Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs)
Description	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. Adverse events were coded using MedDRA version 17.0. Preferred terms linked to injection site AEs are reported. Although a participant may have had 2 or more AEs, the subject is counted only once in each preferred term category. The same subject may appear in different preferred term categories.
Time Frame	Day 1 up to week 52

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	De Novo Participants	Rollover Placebo	Rollover RBP-7000 90 mg	Rollover RBP-7000 120 mg
Arm/Group Description	Participants who were not part of the previous double-blind study. Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart. A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the placebo arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart. A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the RBP-7000 90 mg arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study). A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the RBP-7000 120 mg arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study). A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.
Measure Participants	408	28	31	33
Injection site pain	52 12.7%	2 7.1%	4 12.9%	7 21.2%
Injection site nodule	29 7.1%	1 3.6%	1 3.2%	3 9.1%
Injection site induration	26 6.4%	0 0%	0 0%	3 9.1%
Injection site pruritus	21 5.1%	1 3.6%	0 0%	1 3%
Injection site erythema	4 1%	0 0%	2 6.5%	0 0%
Injection site bruising	5 1.2%	0 0%	0 0%	0 0%
Injection site reaction	3 0.7%	0 0%	0 0%	0 0%
Injection site discolouration	1 0.2%	0 0%	0 0%	1 3%
Injection site discomfort	2 0.5%	0 0%	0 0%	0 0%
Device malfunction	2 0.5%	0 0%	0 0%	0 0%
Implant site nodule	1 0.2%	0 0%	0 0%	0 0%
Influenza like illness	1 0.2%	0 0%	0 0%	0 0%
Infusion site bruising	1 0.2%	0 0%	0 0%	0 0%
Injection site irritation	1 0.2%	0 0%	0 0%	0 0%
Injection site swelling	0 0%	0 0%	1 3.2%	0 0%
Injection site ulcer	1 0.2%	0 0%	0 0%	0 0%

3. Primary Outcome

Title	Participants With Markedly Abnormal Weight Gain Anytime During the Study as Compared to Baseline
Description	Participants who were found to have gain >=7% and >=10% of their baseline weight at any point during the study (including unscheduled assessments) once treatment began.
Time Frame	Baseline (Day 0), Treatment (Day 1 up to Week 52)

Outcome Measure Data

Analysis Population Description

Safety population of study participants with a baseline weight recorded and at least one post-treatment weight recorded.

Arm/Group Title	De Novo Participants	Rollover Placebo	Rollover RBP-7000 90 mg	Rollover RBP-7000 120 mg
Arm/Group Description	Participants who were not part of the previous double-blind study. Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart. A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the placebo arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart. A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the RBP-7000 90 mg arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study). A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the RBP-7000 120 mg arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study). A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.
Measure Participants	386	25	29	30
>=7% increase from baseline	106 26%	3 10.7%	4 12.9%	5 15.2%
>=10% increase from baseline	67 16.4%	3 10.7%	2 6.5%	4 12.1%

4. Secondary Outcome

Title	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score to Days 29, 169 and End of Study
Description	The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor judgement, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score is the sum of all 30 PANSS items and ranges from 30 to 210, with 30 indicating absence of symptoms of schizophrenia and 210 indicating extreme ratings of all 30 symptoms. Negative change from baseline scores indicate improvements in symptoms.
Time Frame	Baseline (Day 0), Day 29, Day 169 and End of Study (approximately Week 52)

Outcome Measure Data

Analysis Population Description

Safety population. Population counts at each timepoint represent participants with an observation at that timepoint (all participants had baseline assessments).

Arm/Group Title	De Novo Participants	Rollover Placebo	Rollover RBP-7000 90 mg	Rollover RBP-7000 120 mg
Arm/Group Description	Participants who were not part of the previous double-blind study. Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart. A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the placebo arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart. A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the RBP-7000 90 mg arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study). A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the RBP-7000 120 mg arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study). A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.
Measure Participants	408	28	31	33
Day 29	-1.2 (5.70)	-4.8 (11.11)	-8.3 (13.43)	-2.4 (10.25)
Day 169	-1.2 (6.84)	-8.2 (18.96)	-10.0 (14.42)	-9.4 (9.62)
End of Study	-0.4 (8.67)	-20.2 (15.59)	-12.5 (15.53)	-10.9 (13.16)

5. Secondary Outcome

Title	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores to End of Study
Description	PANSS subscales: Positive scale assesses 7 items: delusions, conceptual disorganization, hallucinations, excitement, grandiosity, suspiciousness/persecution, and hostility. Scale: 7 (absent) to 49 (extreme psychopathology) Negative scale assesses 7 items: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking. Scale: 7 (absent) to 49 (extreme psychopathology) General Psychopathology scale assesses 16 items: somatic concern, anxiety, guilt feelings, tension, mannerisms and posturing, depression, motor retardation, uncooperativeness, unusual thought content, disorientation, poor attention, lack of judgment and insight, disturbance of volition, poor impulse control, preoccupation, and active social avoidance. Scale: 16 (absent) to 112 (extreme psychopathology) Negative change from baseline scores indicate improvements.
Time Frame	Baseline (Day 0), End of Study (approximately Week 52)

Outcome Measure Data

Analysis Population Description

Safety population. Population counts represent participants with an end of study observation (all participants had baseline assessments).

Arm/Group Title	De Novo Participants	Rollover Placebo	Rollover RBP-7000 90 mg	Rollover RBP-7000 120 mg
Arm/Group Description	Participants who were not part of the previous double-blind study. Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart. A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the placebo arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart. A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the RBP-7000 90 mg arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study). A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the RBP-7000 120 mg arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study). A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.
Measure Participants	197	6	15	15
Positive subscale	-1.3 (3.29)	-7.8 (5.49)	-3.7 (4.08)	-3.7 (3.50)
Negative subscale	1.3 (3.56)	-4.0 (5.93)	-4.1 (4.60)	-0.9 (3.78)
General Psychopathology subscale	-0.4 (5.00)	-8.3 (6.95)	-4.7 (8.99)	-6.4 (7.92)

6. Secondary Outcome

Title	Change From Baseline in Clinical Global Impression - Severity Scores (CGI-S) to Days 29, 169 and End of Study
Description	The CGI-S rating scale is a 7-point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants". Negative change from baseline scores indicate improvement in the severity of illness.
Time Frame	Baseline (Day 0), Baseline (Day 0), Day 29, Day 169 and End of Study (approximately Week 52)

Outcome Measure Data

Analysis Population Description

Safety population. Population counts at each timepoint represent participants with an observation at that timepoint (all participants had baseline assessments).

Arm/Group Title	De Novo Participants	Rollover Placebo	Rollover RBP-7000 90 mg	Rollover RBP-7000 120 mg
Arm/Group Description	Participants who were not part of the previous double-blind study. Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart. A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the placebo arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart. A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the RBP-7000 90 mg arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study). A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.	Participants who were randomized to the RBP-7000 120 mg arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study). A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.
Measure Participants	408	28	31	33
Day 29	-0.0 (0.35)	-0.3 (0.82)	-0.2 (0.80)	-0.1 (0.71)
Day 169	-0.1 (0.48)	-0.3 (1.32)	-0.3 (0.59)	-0.4 (0.87)
End of Study	-0.2 (0.66)	-1.0 (1.10)	-0.5 (0.64)	-0.3 (1.05)

Adverse Events

Time Frame	Day 1 to Week 52
Arm/Group Title	De Novo Participants		Rollover Placebo		Rollover RBP-7000 90 mg		Rollover RBP-7000 120 mg
Arm/Group Description	Participants who were not part of the previous double-blind study. Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart. A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.		Participants who were randomized to the placebo arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart. A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.		Participants who were randomized to the RBP-7000 90 mg arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study). A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.		Participants who were randomized to the RBP-7000 120 mg arm in the double-blind study RB-US-09-0010 prior to entering this study. Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study). A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator.
All Cause Mortality
	De Novo Participants		Rollover Placebo		Rollover RBP-7000 90 mg		Rollover RBP-7000 120 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/408 (0.7%)		1/28 (3.6%)		0/31 (0%)		0/33 (0%)
Serious Adverse Events
	De Novo Participants		Rollover Placebo		Rollover RBP-7000 90 mg		Rollover RBP-7000 120 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/408 (6.1%)		3/28 (10.7%)		3/31 (9.7%)		3/33 (9.1%)
Cardiac disorders
Angina unstable	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Cardiac arrest	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Gastrointestinal disorders
Abdominal pain	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Diarrhoea	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Nausea	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Vomiting	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
General disorders
Non-cardiac chest pain	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Pyrexia	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Infections and infestations
Diverticulitus	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Injury, poisoning and procedural complications
Accidental overdose	0/408 (0%)		1/28 (3.6%)		0/31 (0%)		0/33 (0%)
Hand fracture	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Hypoglycaemia	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Hypokalaemia	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Musculoskeletal and connective tissue disorders
Muscular weakness	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma	0/408 (0%)		0/28 (0%)		0/31 (0%)		1/33 (3%)
Nervous system disorders
Facial paresis	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Psychiatric disorders
Agitation	0/408 (0%)		0/28 (0%)		1/31 (3.2%)		0/33 (0%)
Depressive symptom	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Psychotic disorder	4/408 (1%)		0/28 (0%)		0/31 (0%)		1/33 (3%)
Schizophrenia	5/408 (1.2%)		1/28 (3.6%)		0/31 (0%)		1/33 (3%)
Stress	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Substance-induced psychotic disorder	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Suicidal ideation	3/408 (0.7%)		0/28 (0%)		1/31 (3.2%)		0/33 (0%)
Suicide attempt	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Chronic obstructive pulmonary disease	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Dyspnoea	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Pulmonany embolism	0/408 (0%)		1/28 (3.6%)		0/31 (0%)		0/33 (0%)
Social circumstances
Substance use	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Vascular disorders
Deep vein thrombosis	0/408 (0%)		0/28 (0%)		1/31 (3.2%)		0/33 (0%)
Hypotension	1/408 (0.2%)		0/28 (0%)		0/31 (0%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	De Novo Participants		Rollover Placebo		Rollover RBP-7000 90 mg		Rollover RBP-7000 120 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	228/408 (55.9%)		14/28 (50%)		17/31 (54.8%)		13/33 (39.4%)
Gastrointestinal disorders
Toothache	4/408 (1%)		1/28 (3.6%)		2/31 (6.5%)		1/33 (3%)
General disorders
Fatigue	12/408 (2.9%)		1/28 (3.6%)		3/31 (9.7%)		1/33 (3%)
Injection site erythema	4/408 (1%)		0/28 (0%)		2/31 (6.5%)		0/33 (0%)
Injection site induration	26/408 (6.4%)		0/28 (0%)		0/31 (0%)		3/33 (9.1%)
Injection site nodule	29/408 (7.1%)		1/28 (3.6%)		1/31 (3.2%)		3/33 (9.1%)
Injection site pain	52/408 (12.7%)		2/28 (7.1%)		4/31 (12.9%)		7/33 (21.2%)
Injection site pruritus	21/408 (5.1%)		1/28 (3.6%)		0/31 (0%)		1/33 (3%)
Infections and infestations
Bronchitis	8/408 (2%)		2/28 (7.1%)		1/31 (3.2%)		0/33 (0%)
Upper respiratory tract infection	23/408 (5.6%)		1/28 (3.6%)		2/31 (6.5%)		0/33 (0%)
Investigations
Weight increased	60/408 (14.7%)		1/28 (3.6%)		0/31 (0%)		3/33 (9.1%)
Metabolism and nutrition disorders
Increased appetite	16/408 (3.9%)		0/28 (0%)		1/31 (3.2%)		2/33 (6.1%)
Nervous system disorders
Akathisia	25/408 (6.1%)		2/28 (7.1%)		2/31 (6.5%)		1/33 (3%)
Headache	20/408 (4.9%)		0/28 (0%)		4/31 (12.9%)		1/33 (3%)
Somnolence	17/408 (4.2%)		2/28 (7.1%)		0/31 (0%)		3/33 (9.1%)
Tremor	7/408 (1.7%)		3/28 (10.7%)		0/31 (0%)		0/33 (0%)
Psychiatric disorders
Insomnia	27/408 (6.6%)		1/28 (3.6%)		4/31 (12.9%)		3/33 (9.1%)
Schizophrenia	28/408 (6.9%)		3/28 (10.7%)		2/31 (6.5%)		0/33 (0%)
Reproductive system and breast disorders
Galactorrhoea	11/408 (2.7%)		1/28 (3.6%)		0/31 (0%)		2/33 (6.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.