A Study of Paliperidone Palmitate 6-Month Formulation

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03345342
• Collaborator: (none)
• Enrollment: 841
• Locations: 138
• Arms: 4
• Actual Duration (Months): 29.6
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to demonstrate that injection cycles consisting of a single administration of paliperidone palmitate 6-month (PP6M) are not less effective than 2 sequentially administered injections of paliperidone palmitate 3-month PP3M) (350 or 525 mg eq.) for the prevention of relapse in participants with schizophrenia previously stabilized on corresponding doses of paliperidone palmitate 1-month (PP1M) (100 or 150 mg eq.) or PP3M (350 or 525 mg eq.).

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: PP6M; Drug: PP3M 350 mg eq.; Drug: PP3M 525 mg eq.; Drug: PP1M; Other: Placebo	Phase 3

Detailed Description

The primary hypothesis of this study is that the efficacy of PP6M is non-inferior to PP3M for preventing relapse in participants with schizophrenia who were previously stabilized on corresponding doses of PP1M or PP3M. The study consists of mainly 3 phases: a screening phase (up to 28 days), a maintenance phase (of 1 or 3 months), and a double-blind phase (of 12 months [neither the researchers nor the participants know what treatment the participant is receiving]). Additional/conditional phases include a transition phase (before maintenance phase). Study evaluations include efficacy, pharmacokinetics, pharmacodynamics, and safety. The study duration will vary from approximately 13 months to 19 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 841 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Randomized, Active-controlled, Parallel-group Study of Paliperidone Palmitate 6-Month Formulation
• Actual Study Start Date: Nov 20, 2017
• Actual Primary Completion Date: May 8, 2020
• Actual Study Completion Date: May 8, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PP1M: Transition Phase Participants who previously have not achieved stability with moderate to higher doses of Paliperidone palmitate 1-month (PP1M) or Paliperidone palmitate 3-month (PP3M) will enter into a transition period of up to 4 months. During transition period participants will receive 1 to 5 injections of PP1M 50 to 100 milligrams equivalent (mg eq.). The participants who achieved stability (stability is defined as at least 3 months of injections with the last 2 doses being the same strength) with PP1M 100 mg eq. will precede from transition phase to maintenance phase.	Drug: PP1M; Participants will receive intramuscular injection of PP1M 50 to 150 mg eq.; Other Names: R092670
Experimental: PP1M/PP3M: Maintenance Phase All the participants will receive only 1 dose of PP1M 100 or 150 mg eq. or PP3M 350 or 525 mg eq. The participants will precede from maintenance phase to double-blind phase.	Drug: PP3M 350 mg eq.; Participants will receive intramuscular injection of PP3M 350 mg eq.; Other Names: R092670 ; Drug: PP3M 525 mg eq.; Participants will receive intramuscular injection of PP3M 525 mg eq.; Other Names: R092670 ; Drug: PP1M; Participants will receive intramuscular injection of PP1M 50 to 150 mg eq.; Other Names: R092670
Experimental: PP6M or Placebo: Double-Blind Phase Participants will receive intramuscular injection of PP6M in left gluteal muscle on Day 1 and right gluteal muscle on Day 183 with alternating placebo in right gluteal muscle on Day 92 and left gluteal muscle on Day 274.	Drug: PP6M; Participants will receive intramuscular injection of PP6M.; Other Names: R092670 ; Other: Placebo; Participants will receive matching placebo.
Experimental: PP3M: Double-Blind Phase Participants will receive intramuscular injections of PP3M at dose of 350 mg eq. or 525 mg eq. in left gluteal muscle on Day 1 and 274 and right gluteal muscle on Day 92 and 183.	Drug: PP3M 350 mg eq.; Participants will receive intramuscular injection of PP3M 350 mg eq.; Other Names: R092670 ; Drug: PP3M 525 mg eq.; Participants will receive intramuscular injection of PP3M 525 mg eq.; Other Names: R092670

Outcome Measures

Primary Outcome Measures

1. Time to Relapse During the Double-Blind (DB) Phase [Up to 12 months of DB Phase]

   Time to relapse is time between participant randomization in DB Phase and first documentation of relapse event by end of Month 12 of DB phase. Relapse is defined as: a) Psychiatric hospitalization; b) Positive and Negative Syndrome Scale (PANSS) total score: Increase of 25 percentage (%), 10 point increase in PANSS for 2 analysis separated by 3-7 days if score was greater than (>) 40, less than or equal to (<=)40; c) Participants inflicted knowing self-injury/shown violent behavior leading to suicide, clinically significant injury to him/herself or other person/property; d) Participants had suicidal/homicidal ideation/violent behavior that was clinically significant as per investigator; e) PANSS items P1- delusions, P2- conceptual disorganization, P3-hallucinatory behavior, P6- suspiciousness/ persecution, P7-hostility, G8-uncooperativeness: score: greater than or equal to (>=)5, >=6 for 2 analysis separated by 3-7 days on any items if maximum score for PANSS: <=3 or 4, respectively.

Secondary Outcome Measures

1. Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score [Baseline (DB) to 12 Months of DB Phase]

   The neuropsychiatric symptoms of schizophrenia were assessed using the 30-item PANSS scale, which provides a total score (sum of the scores for all 30 items) and scores for 3 subscales: the 7-item positive-symptom (P) subscale, the 7-item negative-symptom (N) subscale, and the 16-item general-psychopathology symptom (G) subscale. Each item is rated on a scale from 1 (absent) to 7 (extreme). The PANSS total score ranges from 30 (absent disease)-210 (more severe neuropsychiatric symptoms of schizophrenia).

2. Change From Baseline in the Clinical Global Impression - Severity (CGI-S) Score [Baseline (DB) to 12 Months of DB Phase]

   CGI-S is defined as clinician-rated scale that assesses the severity of mental illness on a scale of 0 to 7. Considering total clinical experience, a participant was assessed on severity of mental illness at the time of rating according to:1: normal, not at all ill; 2: borderline mentally ill; 3: mildly ill; 4: moderately ill; 5: markedly ill; 6: severely ill; 7: among the most extremely ill patients. A higher score implies a more severe condition.

3. Change From Baseline in the Personal and Social Performance (PSP) Scale Total Score [Baseline (DB) to 12 Months of DB Phase]

   The Personal and Social Performance (PSP) scale assesses degree of a participant's dysfunction within 4 domains of behavior: 1) socially useful activities, 2) personal and social relationships, 3) self-care, and 4) disturbing and aggressive behavior. Each domain was assessed on a 6-point scale, from 1 (absent) to 6 (very severe) (1 = absent, 2 = mild, 3 = manifest, 4 = marked, 5 = severe, and 6 = very severe). PSP total score was calculated as sum of all the domain scores and ranges from 1 to 100. Participants with score of 71 to 100 have mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision. Higher score indicates better performance.

4. Percentage of Participants With Symptomatic Remission Based on PANSS Score During DB Phase [Up to 12 months of DB Phase]

   Symptomatic remission was defined as achieving intensity level of mild or moderate on PANSS scale by all 8 items as the determinants for symptomatic remission: delusions, unusual thought content, hallucinatory behavior, conceptual disorganization, mannerisms/posturing, blunted affect, social withdrawal, lack of spontaneity. The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self). The PANSS provides a total score and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each item scored on a scale of 1 (absent), 2 (minimal), 3 (mild), 4 (moderate), 5 (moderately severe), 6 (severe) and 7 (extreme). The total score ranges from 30 to 210 and higher score indicates greater severity.

5. Change From Baseline in the Satisfaction With Participants in Social Roles (SPSR) Score [Baseline (DB) to 12 Months of DB Phase]

   The SPSR Short Form 8a is a participant-reported outcome used to assess the satisfaction with participation in social roles. The participants were asked to rate 8 items on 5-point Likert scale, with scores ranging from 8 to 40, where higher scores represents higher satisfaction.

6. Change From Baseline in the Treatment Satisfaction Questionnaire for Medication (TSQM-9) Total Score [Baseline (DB) to 12 Months of DB Phase]

   TSQM-9 consists of 9 questions to assess patients' satisfaction with medication using a range of responses from 1 (extremely dissatisfied) to (7 extremely satisfied). This patient reported outcome provides scores on three parts: effectiveness, convenience, and global satisfaction. The sum of the 9-questions were calculated and used for analysis. The total score ranges from 0 to 63, with higher scores indicating better treatment satisfaction.

7. Change From Baseline in the Simpson-Angus Rating Scale (SAS) Total Score [Baseline (DB) to 12 Months of DB Phase]

   The SAS rates 10 items for general extrapyramidal symptoms (EPS) on a 5-point scale from 0 (normal) to 4 (extreme), including gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head rotation, Glabellar tap, tremor, and salivation. The SAS total score is the average score (total sum of item scores divided by the number of items) and ranges between 0 and 4. Negative change in score indicates improvement. Higher scores denote more severe condition of EPS.

8. Number of Participants With Symptoms of Akathisia Assessed Using Barnes Akathisia Rating Scale (BARS) Score [Up to 12 Months of DB Phase]

   BARS is used to rate observable, restless movements of drug induced akathisia and subjective awareness of restlessness and any distress associated with the akathisia. BARS consists of the following 4 items: objective assessment of akathisia symptoms, subjective assessment of the participants's awareness of inner restlessness, distress restlessness, and global clinical assessment of akathisia. First three items are rated on a 4-point scale ranging from 0 (no abnormal movements or absence of inner restlessness or no distress) to 3 (severe akathisia or awareness of intense compulsion to move most of the time or severe distress). The last item, the global clinical assessment of akathisia, is rated on a 6-point scale, ranging from 0 (no evidence of akathisia) to 5 (severe akathisia).

9. Change From Baseline in the Abnormal Involuntary Movement Scale (AIMS) Total Score [Baseline (DB) to 12 Months of DB Phase]

   AIMS is a 14-item scale. Items 1 to 8 are rated on a 5-point scale ranging from 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Item 9 assesses the participant's incapacitation due to abnormal movements, and item 10 assesses the participant's awareness of the abnormal movements and associated distress. Items 9 and 10 are rated on 5-point scales ranging from 0 (none or no awareness) to 4 (severe or aware, severe distress). Items 11 to 14 are yes/no questions regarding the global judgement and dental status of the participant. The total score is the sum of the scores for the 14 items and the possible total score ranges from 0 to 44. A higher total score is indicative of more severe dyskinetic movements.

10. Number of Participants Based on Columbia Suicide Severity Rating Scale (C-SSRS) Total Score [Baseline and endpoint (12 Months of DB Phase)]

    The C-SSRS is a questionnaire used for suicide risk assessment. Affirmative or negative responses are provided to items 1 to 5 for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods [not plan] without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and items 6 to 10 for suicide behavior (6. Preparatory acts or behavior, 7. Aborted attempt, 8. Interrupted attempt, 9. Actual attempt, 10. Completed suicide). Total score ranges from 1 to 10. Higher scores indicate more severe suicidal ideation.

11. Number of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values During DB Phase [Baseline (DB) to 12 Months of DB Phase]

    Number of participants with treatment-emergent abnormal ECG values were reported. It includes heart rate (abnormally low refers to less than or equal to [<=] 50 beats per minute (bpm) , abnormally high refers greater than or equal to [>=] 100 bpm), pulse rate (PR) interval (abnormally high refers to >= 210 milliseconds [msec]), QRS interval (abnormally Low refers to <= 50, abnormally high refers to >= 120 msec) and QT interval (abnormally low refers to <= 200, abnormally high >= 500 msec).

12. Change From Baseline in the Body Mass Index (BMI) During DB Phase [Baseline (DB) to 12 Months of DB Phase]

    Change from baseline in BMI was reported.

13. Change From Baseline in the Waist Circumference During DB Phase [Baseline (DB) to 12 Months of DB Phase]

    Change from baseline in waist circumference was reported.

14. Change From Baseline in the Body Weight During DB Phase [Baseline (DB) to 12 Months of DB Phase]

    Change from baseline in body weight was reported.

15. Change From Baseline in the Vital Signs (Pulse Rate) During DB Phase [Baseline (DB) to 12 Months of DB Phase]

    Change from baseline vital signs (pulse rate) were reported. This included supine pulse rate, standing pulse rate and supine-standing pulse rate.

16. Change From Baseline in the Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) During DB Phase [Baseline (DB) to 12 Months of DB Phase]

    Change from baseline in vital signs including SBP and DBP (supine/standing) were reported.

17. Change From Baseline in Positive and Syndrome Scale (PANSS) Subscales Score During DB Phase [Baseline (DB) to 12 Months of DB Phase]

    The neuropsychiatric symptoms of schizophrenia were assessed using the 30-item PANSS scale, which provides a total score (sum of the scores for all 30 items) and Scores for 3 subscales, that is, for positive subscale (sum of the scores of all 7 items) and negative subscale (sum of the scores of all 7 items) ranges from 7 (absent) to 49 (extreme psychopathology), and for the general psychopathology subscale (sum of the scores of all 16 items) score ranges from 16 (absent) to 112 (extreme psychopathology).

18. Number of Participants With Treatment-emergent Clinically Significant Abnormal Laboratory Values in Chemistry During DB Phase [Up to 12 Months of DB Phase]

    Number of participants with clinically significant abnormal laboratory values in chemistry included alanine aminotransferase (Unit per Litre [U/L]), albumin (Gram per Litre [g/L]), alkaline phosphatase (U/L), aspartate aminotransferase (U/L), bicarbonate (millimoles per litre [mmol/L]), bilirubin (micromoles per litre [umol/L]), calcium (mmol/L), chloride (mmol/L), cholesterol (mmol/L), creatinine (umol/L), gamma glutamyl transferase (GGT) (U/L), glucose (mmol/L), high-density lipoproteins (HDL) cholesterol (mmol/L), low density lipoproteins (LDL) cholesterol (mmol/L), lactate dehydrogenase (U/L), phosphate (mmol/L), potassium (mmol/L), protein (mmol/L), sodium (mmol/L), triglycerides (mmol/L), urate (umol/L), urea nitrogen (mmol/L) were reported. Here, ABL signifies abnormally low and ABH signifies abnormally high levels.

19. Number of Participants With Treatment-emergent Clinically Significant Abnormal Laboratory Values in Hematology During DB Phase [Up to 12 Months of DB Phase]

    Number of participants with clinically significant abnormal laboratory values in hematology included hemoglobin (Hb), hematocrit (Hct), red blood cell (RBC) count, white blood cell (WBC) count with differential, platelets, hemoglobin A1c. Here, ABL signifies abnormally low and ABH signifies abnormally high levels.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Must meet the diagnostic criteria for schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) for at least 6 months before screening

• Must be receiving treatment with paliperidone palmitate (as either the paliperidone palmitate 1-month (PP1M) or paliperidone palmitate 3-month (PP3M) formulation), or injectable risperidone, or any oral antipsychotic

• Must be able, in the opinion of the investigator, to discontinue any antipsychotic medication other than PP1M) or PP3M during the Screening Phase

• Must have a full Positive and Negative Syndrome Scale (PANSS) score of less than (<) 70 points at screening

• Must have a body mass index (BMI) between 17 and 40 kilogram (kg)/meter (m)^2 (inclusive) and must have a body weight of at least 47 kg at screening

• Must be willing to receive gluteal injections of medication during the Double-blind Phase

Exclusion Criteria

• Must not be receiving any form of involuntary treatment, such as involuntary psychiatric hospitalization, parole-mandated treatment, or court-mandated treatment

• Must not have attempted suicide within 12 months before screening and must not be at imminent risk of suicide or violent behavior, as clinically assessed by the investigator at the time of screening

• Must not have a DSM-5 diagnosis of moderate or severe substance use disorder (except for nicotine and caffeine) within 6 months of screening; however, acute or intermittent substance use prior to screening is not exclusionary, depending upon the clinical judgment of the investigator

• Must not have a history of neuroleptic malignant syndrome or tardive dyskinesia

• Must not have a history of intolerability or severe reactions to moderate or higher doses of antipsychotic medications and must not have any other factors that would, in the judgment of the investigator, indicate that treatment with moderate or higher doses of paliperidone palmitate would be intolerable or unsafe

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Woodland Research Northwest	Rogers	Arkansas	United States	72758
2	California Pharmaceutical Research Institute, Inc.	Anaheim	California	United States	92804
3	ATP Clinical Research	Costa Mesa	California	United States	92626
4	Collaborative NeuroScience Network	Garden Grove	California	United States	92845
5	Synergy East	Lemon Grove	California	United States	91945
6	Pacific Research Partners	Oakland	California	United States	94607
7	SF-Care, Inc	San Rafael	California	United States	94901
8	New Life Medical Research Center, Inc.	Hialeah	Florida	United States	33012
9	Clintex Research Group	Miami	Florida	United States	33135
10	Florida Research Center Inc.	Miami	Florida	United States	33174
11	Olympian Clinical Research	Tampa	Florida	United States	33614
12	Atlanta Center for Medical Research	Atlanta	Georgia	United States	30331
13	Uptown Research Institute	Chicago	Illinois	United States	60640
14	Alexian Behavioral Health Hospital	Hoffman Estates	Illinois	United States	60169
15	Ascension via Christi Research	Wichita	Kansas	United States	67214
16	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
17	Cherry Street Services, Inc.	Grand Rapids	Michigan	United States	49503
18	St. Louis Clinical Trials	Saint Louis	Missouri	United States	63141
19	The Zucker Hillside Hospital	Glen Oaks	New York	United States	11004
20	Clinical Trials of America Inc	Hickory	North Carolina	United States	28601
21	Wexner Medical Center at the Ohio State University	Columbus	Ohio	United States	43210
22	Midwest Clinical Research Center	Dayton	Ohio	United States	45417
23	University of Pennsylvania Medical Center	Philadelphia	Pennsylvania	United States	19104
24	Future Search Trials of Dallas	Dallas	Texas	United States	75231
25	Psychiatric and Behavioral Solutions	Salt Lake City	Utah	United States	84105-2425
26	Fundación para el Estudio y Tratamiento de las Enfermedades Mentales	Ciudad Autónoma De Buenos Aires		Argentina	C1133AAH
27	CEN	Cordoba		Argentina	X5004FJF
28	Sanatorio Prof. Leon S. Morra	Cordoba		Argentina	X5009BIN
29	Instituto de Neurociencias San Agustín	La Plata		Argentina	1900
30	Clinica Privada de Salud Mental Santa Teresa de Ávila	La Plata		Argentina	B1904ADM
31	C.I.A.P. (Centro de investigación y Asistencia en Psiquiatría)	Rosario		Argentina	2000
32	The Lyell McEwin Hospital	Elizabeth Vale		Australia	5112
33	Neuro Trials Victoria	Noble Park		Australia	3174
34	Trial Tech Tecnologia em Pesquisas com Medicamentos	Curitiba		Brazil	80240-280
35	Instituto Bairral de Psiquiatria	Itapira		Brazil	13970-905
36	Hospital de Clínicas de Porto Alegre	Porto Alegre		Brazil	90035-903
37	Centro de Psiquiatria e Pesquisas Sandra Ruschel	Rio de Janeiro		Brazil	22270-060
38	Proesq - Unifesp	Sao Paulo		Brazil	04020-060
39	CPQuali Pesquisa Clinica LTDA ME	São Paulo		Brazil	01228-900
40	Instituto de Psiquiatria - Hcfmusp	São Paulo		Brazil	05403010
41	Mental Health Center Prof. Dr. Ivan Temkov	Bourgas		Bulgaria	8001
42	State Psychiatric Hospital Pazardzhik	Pazardzhik		Bulgaria	4400
43	UMHAT 'Sveti Georgi'-Plovdiv	Plovdiv		Bulgaria	4002
44	State Psychiatric HospitalDr.Georgi Kissiov	Radnevo		Bulgaria	6260
45	Centre for Mental Health Prof.N.Shipkovenski EOOD	Sofia		Bulgaria	1377
46	Medical Center Intermedica, OOD	Sofia		Bulgaria	1680
47	Psychiatricka ambulance, MUDr. Marta Holanova	Brno		Czechia	61500
48	NeuropsychiatrieHK, s.r.o.	Hradec Kralove-Vekose		Czechia	50341
49	A-Shine s.r.o.	Plzen		Czechia	31200
50	Institut Neuropsychiatricke pece	Prague		Czechia	18600
51	Psychiatricka ambulance MUDr. Simona Papezova	Prague		Czechia	19000
52	PRAGTIS s.r.o.	Praha 2		Czechia	12000
53	C.H.S. Charles Perrens	Bordeaux		France	33076
54	CHRU La Colombière	Montpellier		France	34090
55	CHU Caremeau	Nimes Cedex 9		France	30029
56	Hopital Sainte Anne	Paris		France	75674
57	Hôpital Sainte Musse	Toulon Cedex		France	83000
58	Kwai Chung Hospital	Hong Kong		Hong Kong
59	Queen Mary Hospital	Hong Kong		Hong Kong
60	Józsefvarosi Szent Kozma Egészségügyi Központ	Budapest		Hungary	1084
61	Petz Aladar Megyei Oktato Korhaz	Győr		Hungary	9023
62	Bács-Kiskun Megyei Kórház a Szegedi Tudományegyetem Általános Orvostudományi Kar Oktató Kórháza	Kalocsa		Hungary	6300
63	CRU Hungary Kft.	Miskolc		Hungary	3529
64	Ratandeep Multispeciality Hospital	Ahmedabad		India	380008
65	Sri Ramachandra Medical Centre	Chennai		India	600116
66	Asha hospital	Hyderabad		India	500034
67	Ahana Hospitals	Madurai		India	625020
68	Vinaya Hospital and Research Center	Mangalore		India	575003
69	Kasturba Medical College Hospital	Manipal		India	576104
70	Jehangir Clinical Development Center Pvt Ltd	Pune		India	411001
71	Deva Institute of Health Care and Research Pvt Ltd	Varanasi		India	221005
72	Clinica Psichiatrica - Università di Cagliari	Cagliari		Italy	09127
73	Dipartimento di Salute Mentale	Lecce		Italy	73100
74	Seconda Universita degli Studi di Napoli - Azienda Ospedaliera Universitaria	Napoli		Italy	80138
75	Universita degli Studi di Roma 'La Sapienza' - Azienda Ospedaliera Sant Andrea	Roma		Italy	00189
76	Chonnam National University Hospital	Gwangju		Korea, Republic of	61469
77	Chonbuk National Univ Hospital	Jeonju		Korea, Republic of	54907
78	CHA Bundang Medical Center, CHA University	Seongnam		Korea, Republic of	13496
79	Seoul National University Hospital	Seoul		Korea, Republic of	03080
80	Hospital Bahagia Ulu Kinta	Ipoh		Malaysia	31250
81	Hospital Kuala Lumpur	Kuala Lumpur		Malaysia	50586
82	University Malaya Medical Centre	Kuala Lumpur		Malaysia	59100
83	Sarawak General Hospital	Kuching		Malaysia	93586
84	Gabipros SC.	Mexico City		Mexico	07810
85	Instituto Neuropsique	Monterrey		Mexico	64610
86	Centro de Estudios Clinicos y Especialidades Medicas, S.C.	Monterrey		Mexico	64620
87	Infosame/Research	Monterrey		Mexico	64710
88	Centro de Atención e Investigación Cardiovascular del Potosí, S.C.	San Luis Potosí		Mexico	78200
89	Mlynowamed Specjalistyczny Psychiatryczny Gabinet Lekarski Joanna Lazarczyk	Bialystok		Poland	15-404
90	Wlokiennicza MED Specjalistyczna Praktyka Lekarska dr n.med. Tomasz Markowski	Bialystok		Poland	15-464
91	Zespol Opieki Zdrowotnej w Chelmnie	Chelmno		Poland	86-200
92	Centrum Badań Klinicznych PI-House sp. z o.o.	Gdansk		Poland	80-546
93	Szpital Specjalistyczny im. H. Klimontowicza, Oddzial Psychiatryczny	Gorlice		Poland	38-300
94	Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS	Leszno		Poland	64-100
95	Centrum Medyczne Luxmed Sp z o o	Lublin		Poland	20-109
96	Poradnia Zdrowia Psychicznego 'Syntonia' w Pruszczu Gdanskim	Pruszcz Gdanski		Poland	83-000
97	Mazowieckie Specjalistyczne Centrum Zdrowia im. Prof. Jana Mazurkiewicza w Pruszkowie	Pruszkow		Poland	05-802
98	Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu	Torun		Poland	87-100
99	Sverdlovsk Regional Clinical Psychiatric Hospital	Ekaterinburg		Russian Federation
100	Clinical Psychiatric Hospital #3 Named After V.A. Gilyarovsky	Moscow		Russian Federation	107076
101	Psychiatric Clinical hospital 1 named after N.A. Alekseev	Moscow		Russian Federation	117152
102	Nizny Novgorod clinical psychiatric hospital 1	Nizny Novgorod		Russian Federation	603155
103	SHI 'Saratov City Clinical Hospital 2 n.a V.I. Razumovsky	Saratov		Russian Federation	410028
104	Saratov Regional Psychiatric hospital named after St. Sofia	Saratov		Russian Federation	410060
105	Psychoneurological Dispensary of Frunzensky District	St-Petersburg		Russian Federation	190013
106	Psychoneurological dispensary 10	St-Petersburg		Russian Federation	190121
107	St-Petersburg Bekhterev Psychoneurological Research Institute	St-Petersburg		Russian Federation	192109
108	Psychoneurological dispensary 1	St-Petersburg		Russian Federation	199178
109	Psychoneurological Dispensary #4	St.Peterburg		Russian Federation	197110
110	Research Institute of Mental Health	Tomsk		Russian Federation	634014
111	Flexivest 14 Research	Cape Town		South Africa	7550
112	Gert Bosch - Pretoria South Africa	Pretoria		South Africa	0042
113	Juan Schrönen - Western Cape South Africa	Welgemoed		South Africa	7530
114	Hosp. Univ. Vall D Hebron	Barcelona		Spain	08035
115	Inst. Internac. Neurociencias Aplicadas	Barcelona		Spain	8006
116	Hosp. Univ. de Basurto	Bilbao		Spain	48013
117	Centro Salud Mental La Corredoria	Oviedo		Spain	33011
118	Hosp. El Bierzo	Ponferrada		Spain	24404
119	Hosp. Clinico Univ. de Valencia	Valencia		Spain	46010
120	Hosp. Prov. de Zamora	Zamora		Spain	49021
121	National Cheng Kung University Hospital	Tainan		Taiwan	70403
122	Mackay Memorial Hospital	Taipei		Taiwan	10449
123	Taipei Veterans General Hospital	Taipei		Taiwan	11217
124	Chang Gung Memorial Hospital	Taoyuan		Taiwan	333
125	Abdurrah Yurtarslan Training and Research Hospital	Ankara		Turkey	6200
126	Ankara Numune Research and Training Hospital	Ankara		Turkey	6800
127	Erenkoy Mental Health Hospital	Istanbul		Turkey	34736
128	Selcuk University, Medical School, Department of Psychiatry	Konya		Turkey	42130
129	Sakarya University Medical Faculty Psychiatry Department	Sakarya		Turkey	54187
130	MNCE of Kyiv RC Regional Psychiatric and Narcological Medical Association	Glevakha		Ukraine	8630
131	Mnpe of Kharkiv Regional Council 'Regional Clinical Psychiatric Hospital #3'	Kharkiv		Ukraine	61068
132	CNPE'Kherson Regional Institution of Mental Care'of Kherson Regional Council	Kherson		Ukraine	73488
133	Kyiv Territorial Medical Incorporation 'Psychiatry'	Kyiv		Ukraine	04080
134	Municipal Institution 'Lviv Regional Clinical Psycho-Neurological Dispensary'	Lviv		Ukraine	79017
135	CNCE of the Lviv Regional Council 'Lviv Regional Clinical Psychiatric Hospital'	Lviv		Ukraine	79021
136	CNCE Odesa regional psychiatric hospital #2 Odesa regional council	Oleksandrivka		Ukraine	67513
137	CNCE 'Cherkasy Regional Psychiatric Hospital of Cherkasy Regional Council'	Smila		Ukraine	20708
138	CNCE 'Vinnytsya RC Psychoneurological Hospital n.a. O.I. Yushchenko Vinnytsya RC'	Vinnytsia		Ukraine	21005

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

• Study Protocol - Feb 11, 2019
• Statistical Analysis Plan - May 26, 2020

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT03345342
• Other Study ID Numbers: CR108390; R092670PSY3015; 2017-001941-28
• First Posted: Nov 17, 2017
• Last Update Posted: Dec 9, 2021
• Last Verified: Nov 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Schizophrenia

Study Results

Participant Flow

Pre-assignment Detail

Total 841 participants were enrolled, out of which 838 participants received treatment. 2 participants were enrolled but did not receive treatment and 1 participant withdrew from the Open-label Phase and as permitted per the protocol, re-entered the study (under a different participant identifier) and was counted twice in the total. Per the rules specified in statistical analysis plan, only data collected during the second study participation was included in data summary for this participant.

Arm/Group Title	Open-Label (OL) PP1M/PP3M	Double-blind PP3M	Double-blind PP6M	Follow-up (FU) Phase PP3M	Follow-up Phase PP6M
Arm/Group Description	Participants previously treated with oral antipsychotics, or injectable risperidone, or a moderate or higher dose of paliperidone palmitate 1-month (PP1M) with previous initiation but without previous stabilization (where stabilization was defined as at least 3 months of injections with the last 2 doses being the same strength) received 1 to 5 intramuscular (IM) injections of PP1M 50 to 150 milligrams equivalent (mg eq.). Participants received single dose of IM injection of PP1M as 100 or 150 mg eq. or PP3M as 350 or 525 mg eq during the OL-maintenance phase.	Participants received 4 doses of PP3M (350 or 525 mg eq. IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq. IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.	Participants who have received at least 1 dose of PP3M (350 or 525 mg eq.) IM injection during double-blind phase but then have relapsed or have met other relevant conditions for withdrawal or discontinuation can participate in the follow-up phase PP3M (350 or 525 mg eq.) IM injection for up to 12 months for evaluating efficacy and safety.	Participants received PP6M (700 or 1000 mg eq.) IM injection for up to 12 months for evaluating efficacy and safety.
Period Title: Open-Label Phase
STARTED	838	0	0	0	0
COMPLETED	702	0	0	0	0
NOT COMPLETED	136	0	0	0	0
Period Title: Open-Label Phase
STARTED	0	224	478	0	0
COMPLETED	0	202	416	0	0
NOT COMPLETED	0	22	62	0	0
Period Title: Open-Label Phase
STARTED	0	0	0	42	109
COMPLETED	0	0	0	34	78
NOT COMPLETED	0	0	0	8	31

Baseline Characteristics

Arm/Group Title	Open-Label (OL) PP1M/PP3M
Arm/Group Description	Participants previously treated with oral antipsychotics, or injectable risperidone, or a moderate or higher dose of paliperidone palmitate 1-month (PP1M) with previous initiation but without previous stabilization (where stabilization was defined as at least 3 months of injections with the last 2 doses being the same strength) received 1 to 5 intramuscular (IM) injections of PP1M 50 to 150 milligrams equivalent (mg eq.). Participants received single dose of IM injection of PP1M as 100 or 150 mg eq. or PP3M as 350 or 525 mg eq during the OL-maintenance phase.
Overall Participants	838
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.8 (11.68)
Sex: Female, Male (Count of Participants)
Female	285 34%
Male	553 66%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	118 14.1%
Not Hispanic or Latino	710 84.7%
Unknown or Not Reported	10 1.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.1%
Asian	111 13.2%
Native Hawaiian or Other Pacific Islander	3 0.4%
Black or African American	106 12.6%
White	606 72.3%
More than one race	5 0.6%
Unknown or Not Reported	6 0.7%
Region of Enrollment (Count of Participants)
ARGENTINA	55 6.6%
AUSTRALIA	4 0.5%
BRAZIL	90 10.7%
BULGARIA	46 5.5%
CZECH REPUBLIC	45 5.4%
FRANCE	7 0.8%
HONG KONG	4 0.5%
HUNGARY	20 2.4%
INDIA	42 5%
ITALY	8 1%
KOREA, REPUBLIC OF	4 0.5%
MALAYSIA	22 2.6%
MEXICO	23 2.7%
POLAND	68 8.1%
RUSSIAN FEDERATION	139 16.6%
SPAIN	29 3.5%
TAIWAN	31 3.7%
TURKEY	26 3.1%
UKRAINE	50 6%
UNITED STATES	125 14.9%

Outcome Measures

1. Primary Outcome

Title	Time to Relapse During the Double-Blind (DB) Phase
Description	Time to relapse is time between participant randomization in DB Phase and first documentation of relapse event by end of Month 12 of DB phase. Relapse is defined as: a) Psychiatric hospitalization; b) Positive and Negative Syndrome Scale (PANSS) total score: Increase of 25 percentage (%), 10 point increase in PANSS for 2 analysis separated by 3-7 days if score was greater than (>) 40, less than or equal to (<=)40; c) Participants inflicted knowing self-injury/shown violent behavior leading to suicide, clinically significant injury to him/herself or other person/property; d) Participants had suicidal/homicidal ideation/violent behavior that was clinically significant as per investigator; e) PANSS items P1- delusions, P2- conceptual disorganization, P3-hallucinatory behavior, P6- suspiciousness/ persecution, P7-hostility, G8-uncooperativeness: score: greater than or equal to (>=)5, >=6 for 2 analysis separated by 3-7 days on any items if maximum score for PANSS: <=3 or 4, respectively.
Time Frame	Up to 12 months of DB Phase

Outcome Measure Data

Analysis Population Description

DB Intent-to-Treat (ITT) analysis set included participants who were randomly assigned to paliperidone palmitate 6-month (PP6M) /paliperidone palmitate 3-month (PP3M) during DB Phase, received at least 1 dose of PP6M/PP3M.

Arm/Group Title	DB PP3M	DB PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 milligrams equivalent [mg eq.]) intramuscular (IM) injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	224	478
Median (95% Confidence Interval) [Days]	NA	NA

2. Secondary Outcome

Title	Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score
Description	The neuropsychiatric symptoms of schizophrenia were assessed using the 30-item PANSS scale, which provides a total score (sum of the scores for all 30 items) and scores for 3 subscales: the 7-item positive-symptom (P) subscale, the 7-item negative-symptom (N) subscale, and the 16-item general-psychopathology symptom (G) subscale. Each item is rated on a scale from 1 (absent) to 7 (extreme). The PANSS total score ranges from 30 (absent disease)-210 (more severe neuropsychiatric symptoms of schizophrenia).
Time Frame	Baseline (DB) to 12 Months of DB Phase

Outcome Measure Data

Analysis Population Description

DB ITT analysis set included all participants who were randomly assigned to treatment group of either PP6M or PP3M during the DB Phase and received at least 1 dose of PP6M/PP3M. Here 'N' (number of participants analyzed), signifies participants who were evaluable for this outcome measure.

Arm/Group Title	DB PP3M	DB PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	220	473
Mean (Standard Deviation) [units on a scale]	-1.6 (7.40)	-1.8 (8.92)

3. Secondary Outcome

Title	Change From Baseline in the Clinical Global Impression - Severity (CGI-S) Score
Description	CGI-S is defined as clinician-rated scale that assesses the severity of mental illness on a scale of 0 to 7. Considering total clinical experience, a participant was assessed on severity of mental illness at the time of rating according to:1: normal, not at all ill; 2: borderline mentally ill; 3: mildly ill; 4: moderately ill; 5: markedly ill; 6: severely ill; 7: among the most extremely ill patients. A higher score implies a more severe condition.
Time Frame	Baseline (DB) to 12 Months of DB Phase

Outcome Measure Data

Analysis Population Description

DB ITT analysis set included all participants who were randomly assigned to treatment group of either PP6M or PP3M during the DB Phase and received at least 1 dose of PP6M/PP3M. Here 'N' (number of participants analyzed), included all participants who were evaluable for this outcome measure.

Arm/Group Title	DB PP3M	DB PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	221	475
Mean (Standard Deviation) [units on a scale]	0.0 (0.63)	0.0 (0.70)

4. Secondary Outcome

Title	Change From Baseline in the Personal and Social Performance (PSP) Scale Total Score
Description	The Personal and Social Performance (PSP) scale assesses degree of a participant's dysfunction within 4 domains of behavior: 1) socially useful activities, 2) personal and social relationships, 3) self-care, and 4) disturbing and aggressive behavior. Each domain was assessed on a 6-point scale, from 1 (absent) to 6 (very severe) (1 = absent, 2 = mild, 3 = manifest, 4 = marked, 5 = severe, and 6 = very severe). PSP total score was calculated as sum of all the domain scores and ranges from 1 to 100. Participants with score of 71 to 100 have mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision. Higher score indicates better performance.
Time Frame	Baseline (DB) to 12 Months of DB Phase

Outcome Measure Data

Analysis Population Description

DB ITT analysis set included all participants who were randomly assigned to treatment group of either PP6M or PP3M during the DB Phase and received at least 1 dose of PP6M/PP3M. Here 'N' (number of participants analyzed), included all participants who were evaluable for this outcome measure.

Arm/Group Title	DB PP3M	DB PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	220	473
Mean (Standard Deviation) [units on a scale]	1.1 (8.11)	1.0 (7.12)

5. Secondary Outcome

Title	Percentage of Participants With Symptomatic Remission Based on PANSS Score During DB Phase
Description	Symptomatic remission was defined as achieving intensity level of mild or moderate on PANSS scale by all 8 items as the determinants for symptomatic remission: delusions, unusual thought content, hallucinatory behavior, conceptual disorganization, mannerisms/posturing, blunted affect, social withdrawal, lack of spontaneity. The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self). The PANSS provides a total score and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each item scored on a scale of 1 (absent), 2 (minimal), 3 (mild), 4 (moderate), 5 (moderately severe), 6 (severe) and 7 (extreme). The total score ranges from 30 to 210 and higher score indicates greater severity.
Time Frame	Up to 12 months of DB Phase

Outcome Measure Data

Analysis Population Description

DB ITT included all participants who were randomly assigned to treatment group of either PP6M or PP3M, received at least 1 dose of PP6M/PP3M.

Arm/Group Title	DB PP3M	DB PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	224	478
Number [Percentage of participants]	70.1 8.4%	66.3 NaN

6. Secondary Outcome

Title	Change From Baseline in the Satisfaction With Participants in Social Roles (SPSR) Score
Description	The SPSR Short Form 8a is a participant-reported outcome used to assess the satisfaction with participation in social roles. The participants were asked to rate 8 items on 5-point Likert scale, with scores ranging from 8 to 40, where higher scores represents higher satisfaction.
Time Frame	Baseline (DB) to 12 Months of DB Phase

Outcome Measure Data

Analysis Population Description

DB ITT analysis set included all participants who were randomly assigned to treatment group of either PP6M or PP3M during the DB Phase and received at least 1 dose of PP6M/PP3M. Here 'N' (number of participants analyzed), included all participants who were evaluable for this outcome measure.

Arm/Group Title	DB PP3M	DB PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	70	154
Mean (Standard Deviation) [units on a scale]	0.9 (7.15)	0.6 (6.58)

7. Secondary Outcome

Title	Change From Baseline in the Treatment Satisfaction Questionnaire for Medication (TSQM-9) Total Score
Description	TSQM-9 consists of 9 questions to assess patients' satisfaction with medication using a range of responses from 1 (extremely dissatisfied) to (7 extremely satisfied). This patient reported outcome provides scores on three parts: effectiveness, convenience, and global satisfaction. The sum of the 9-questions were calculated and used for analysis. The total score ranges from 0 to 63, with higher scores indicating better treatment satisfaction.
Time Frame	Baseline (DB) to 12 Months of DB Phase

Outcome Measure Data

Analysis Population Description

DB ITT analysis set included all participants who were randomly assigned to treatment group of either PP6M or PP3M during the DB Phase and received at least 1 dose of PP6M/PP3M. Here 'N' (number of participants analyzed), included all participants who were evaluable for this outcome measure.

Arm/Group Title	DB PP3M	DB PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	121	279
Effectiveness	6.0 (21.18)	3.6 (19.49)
Convenience	3.4 (17.76)	1.1 (15.30)
Overall satisfaction	2.5 (19.29)	0.5 (20.02)

8. Secondary Outcome

Title	Change From Baseline in the Simpson-Angus Rating Scale (SAS) Total Score
Description	The SAS rates 10 items for general extrapyramidal symptoms (EPS) on a 5-point scale from 0 (normal) to 4 (extreme), including gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head rotation, Glabellar tap, tremor, and salivation. The SAS total score is the average score (total sum of item scores divided by the number of items) and ranges between 0 and 4. Negative change in score indicates improvement. Higher scores denote more severe condition of EPS.
Time Frame	Baseline (DB) to 12 Months of DB Phase

Outcome Measure Data

Analysis Population Description

DB ITT analysis set included all participants who were randomly assigned to treatment group of either PP6M or PP3M during the DB Phase and received at least 1 dose of PP6M/PP3M. Here 'N' (number of participants analyzed), included all participants who were evaluable for this outcome measure.

Arm/Group Title	DB PP3M	DB PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	220	477
Median (Full Range) [units on a scale]	0.00	0.00

9. Secondary Outcome

Title	Number of Participants With Symptoms of Akathisia Assessed Using Barnes Akathisia Rating Scale (BARS) Score
Description	BARS is used to rate observable, restless movements of drug induced akathisia and subjective awareness of restlessness and any distress associated with the akathisia. BARS consists of the following 4 items: objective assessment of akathisia symptoms, subjective assessment of the participants's awareness of inner restlessness, distress restlessness, and global clinical assessment of akathisia. First three items are rated on a 4-point scale ranging from 0 (no abnormal movements or absence of inner restlessness or no distress) to 3 (severe akathisia or awareness of intense compulsion to move most of the time or severe distress). The last item, the global clinical assessment of akathisia, is rated on a 6-point scale, ranging from 0 (no evidence of akathisia) to 5 (severe akathisia).
Time Frame	Up to 12 Months of DB Phase

Outcome Measure Data

Analysis Population Description

DB ITT analysis set included all participants who were randomly assigned to treatment group of either PP6M or PP3M during the DB Phase and received at least 1 dose of PP6M/PP3M.

Arm/Group Title	DB PP3M	DB PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	224	478
Global Clinical Assessment	185 22.1%	380 NaN
Objective	185 22.1%	380 NaN
Subjective (Awareness)	185 22.1%	380 NaN
Subjective (Distress)	185 22.1%	380 NaN

10. Secondary Outcome

Title	Change From Baseline in the Abnormal Involuntary Movement Scale (AIMS) Total Score
Description	AIMS is a 14-item scale. Items 1 to 8 are rated on a 5-point scale ranging from 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Item 9 assesses the participant's incapacitation due to abnormal movements, and item 10 assesses the participant's awareness of the abnormal movements and associated distress. Items 9 and 10 are rated on 5-point scales ranging from 0 (none or no awareness) to 4 (severe or aware, severe distress). Items 11 to 14 are yes/no questions regarding the global judgement and dental status of the participant. The total score is the sum of the scores for the 14 items and the possible total score ranges from 0 to 44. A higher total score is indicative of more severe dyskinetic movements.
Time Frame	Baseline (DB) to 12 Months of DB Phase

Outcome Measure Data

Analysis Population Description

DB ITT analysis set included all participants who were randomly assigned to treatment group of either PP6M or PP3M during the DB Phase and received at least 1 dose of PP6M/PP3M. Here 'N' (number of participants analyzed), included all participants who were evaluable for this outcome measure.

Arm/Group Title	Double-blind (DB) PP3M	Double-blind (DB) PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	221	477
Median (Full Range) [units on a scale]	0.0	0.0

11. Secondary Outcome

Title	Number of Participants Based on Columbia Suicide Severity Rating Scale (C-SSRS) Total Score
Description	The C-SSRS is a questionnaire used for suicide risk assessment. Affirmative or negative responses are provided to items 1 to 5 for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods [not plan] without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and items 6 to 10 for suicide behavior (6. Preparatory acts or behavior, 7. Aborted attempt, 8. Interrupted attempt, 9. Actual attempt, 10. Completed suicide). Total score ranges from 1 to 10. Higher scores indicate more severe suicidal ideation.
Time Frame	Baseline and endpoint (12 Months of DB Phase)

Outcome Measure Data

Analysis Population Description

DB ITT analysis set included all participants who were randomly assigned to treatment group of either PP6M or PP3M during the DB Phase and received at least 1 dose of PP6M/PP3M. Here 'n' (number analyzed) included all evaluable participants who were analyzed for specified categories.

Arm/Group Title	DB PP3M	DB PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	224	478
Baseline (0= No event)	221 26.4%	477 NaN
Baseline (1= Wish to be dead)	3 0.4%	0 NaN
Baseline (2= Non-specific suicidal thought)	0 0%	1 NaN
Baseline (3= Suicidal ideation-no intent)	0 0%	0 NaN
Baseline (4= Ideation with intent, no plan)	0 0%	0 NaN
Baseline (5= Ideation with plan/intent)	0 0%	0 NaN
Baseline (6= Preparatory acts/behavior)	0 0%	0 NaN
Baseline (7= Aborted attempt)	0 0%	0 NaN
Baseline (8= Interrupted attempt)	0 0%	0 NaN
Baseline (9= Actual attempt)	0 0%	0 NaN
Baseline (10= Suicide)	0 0%	0 NaN
End Point (0= No event)	218 26%	471 NaN
End Point (1= Wish to be dead)	1 0.1%	1 NaN
End Point (2= Non-specific suicidal thought)	0 0%	0 NaN
End Point (3= Suicidal ideation-no intent)	0 0%	1 NaN
End Point (4= Ideation with intent, no plan)	1 0.1%	0 NaN
End Point (5= Ideation with plan/intent)	1 0.1%	2 NaN
End Point (6= Preparatory acts/behavior)	0 0%	0 NaN
End Point (7= Aborted attempt)	0 0%	0 NaN
End Point (8= Interrupted attempt)	0 0%	0 NaN
End Point (9= Actual attempt)	0 0%	1 NaN
End Point (10= Suicide)	0 0%	0 NaN

12. Secondary Outcome

Title	Number of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values During DB Phase
Description	Number of participants with treatment-emergent abnormal ECG values were reported. It includes heart rate (abnormally low refers to less than or equal to [<=] 50 beats per minute (bpm) , abnormally high refers greater than or equal to [>=] 100 bpm), pulse rate (PR) interval (abnormally high refers to >= 210 milliseconds [msec]), QRS interval (abnormally Low refers to <= 50, abnormally high refers to >= 120 msec) and QT interval (abnormally low refers to <= 200, abnormally high >= 500 msec).
Time Frame	Baseline (DB) to 12 Months of DB Phase

Outcome Measure Data

Analysis Population Description

Double-blind safety analysis set (DB safety) included all participants who were randomly assigned to treatment group of either PP6M or PP3M during the DB Phase and received at least 1 dose of PP6M/PP3M. Here 'N' (number of participants analyzed), included all participants who were evaluable for this outcome measure.

Arm/Group Title	DB PP3M	DB PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	220	474
Heart Rate value <=50	5 0.6%	9 NaN
Heart Rate value >=100	20 2.4%	36 NaN
PR Duration value >= 210	3 0.4%	8 NaN
QRS Duration value <= 50	0 0%	0 NaN
QRS Duration value >= 120	1 0.1%	2 NaN
QT Duration value <= 200	0 0%	0 NaN
QT Duration value >= 500	0 0%	0 NaN

13. Secondary Outcome

Title	Change From Baseline in the Body Mass Index (BMI) During DB Phase
Description	Change from baseline in BMI was reported.
Time Frame	Baseline (DB) to 12 Months of DB Phase

Outcome Measure Data

Analysis Population Description

DB ITT analysis set included all participants who were randomly assigned to treatment group of either PP6M or PP3M during the DB Phase and received at least 1 dose of PP6M/PP3M. Here 'N' (number of participants analyzed), included all participants who were evaluable for this outcome measure.

Arm/Group Title	DB PP3M	DB PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	219	473
Mean (Standard Deviation) [kilogram per meter square (kg/m^2)]	0.3 (1.78)	0.0 (1.72)

14. Secondary Outcome

Title	Change From Baseline in the Waist Circumference During DB Phase
Description	Change from baseline in waist circumference was reported.
Time Frame	Baseline (DB) to 12 Months of DB Phase

Outcome Measure Data

Analysis Population Description

DB ITT analysis set included all participants who were randomly assigned to treatment group of either PP6M or PP3M during the DB Phase and received at least 1 dose of PP6M/PP3M. Here 'N' (number of participants analyzed), included all participants who were evaluable for this outcome measure.

Arm/Group Title	DB PP3M	DB PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	219	473
Mean (Standard Deviation) [centimeter (cm)]	0.82 (5.137)	0.37 (5.157)

15. Secondary Outcome

Title	Change From Baseline in the Body Weight During DB Phase
Description	Change from baseline in body weight was reported.
Time Frame	Baseline (DB) to 12 Months of DB Phase

Outcome Measure Data

Analysis Population Description

DB ITT analysis set included all participants who were randomly assigned to treatment group of either PP6M or PP3M during the DB Phase and received at least 1 dose of PP6M/PP3M. Here 'N' (number of participants analyzed), included all participants who were evaluable for this outcome measure.

Arm/Group Title	DB PP3M	DB PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	219	473
Mean (Standard Deviation) [kilogram (kg)]	0.96 (5.103)	0.10 (4.959)

16. Secondary Outcome

Title	Change From Baseline in the Vital Signs (Pulse Rate) During DB Phase
Description	Change from baseline vital signs (pulse rate) were reported. This included supine pulse rate, standing pulse rate and supine-standing pulse rate.
Time Frame	Baseline (DB) to 12 Months of DB Phase

Outcome Measure Data

Analysis Population Description

DB ITT analysis set included all participants who were randomly assigned to treatment group of either PP6M or PP3M during the DB Phase and received at least 1 dose of PP6M/PP3M. Here 'N' (number of participants analyzed), included all participants who were evaluable for this outcome measure.

Arm/Group Title	Double-blind (DB) PP3M	Double-blind (DB) PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	219	473
Supine Pulse Rate	1.2 (11.57)	0.6 (11.56)
Standing Pulse Rate	2.6 (12.28)	0.9 (12.60)
Pulse Rate (Standing-Supine)	1.5 (8.85)	0.2 (8.31)

17. Secondary Outcome

Title	Change From Baseline in the Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) During DB Phase
Description	Change from baseline in vital signs including SBP and DBP (supine/standing) were reported.
Time Frame	Baseline (DB) to 12 Months of DB Phase

Outcome Measure Data

Analysis Population Description

DB ITT analysis set included all participants who were randomly assigned to treatment group of either PP6M or PP3M during the DB Phase and received at least 1 dose of PP6M/PP3M. Here 'N' (number of participants analyzed), included all participants who were evaluable for this outcome measure.

Arm/Group Title	Double-blind (DB) PP3M	Double-blind (DB) PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	219	473
Supine SBP	-0.3 (13.14)	0.6 (9.96)
Standing SBP	0.8 (12.08)	1.3 (10.40)
SBP (Standing-Supine)	1.0 (9.83)	0.6 (7.32)
Supine DBP	0.1 (9.25)	-0.4 (7.49)
Standing DBP	0.3 (9.39)	0.4 (7.48)
DBP (Standing-Supine)	0.2 (7.79)	0.7 (6.43)

18. Secondary Outcome

Title	Change From Baseline in Positive and Syndrome Scale (PANSS) Subscales Score During DB Phase
Description	The neuropsychiatric symptoms of schizophrenia were assessed using the 30-item PANSS scale, which provides a total score (sum of the scores for all 30 items) and Scores for 3 subscales, that is, for positive subscale (sum of the scores of all 7 items) and negative subscale (sum of the scores of all 7 items) ranges from 7 (absent) to 49 (extreme psychopathology), and for the general psychopathology subscale (sum of the scores of all 16 items) score ranges from 16 (absent) to 112 (extreme psychopathology).
Time Frame	Baseline (DB) to 12 Months of DB Phase

Outcome Measure Data

Analysis Population Description

DB ITT analysis set included all participants who were randomly assigned to treatment group of either PP6M or PP3M during the DB Phase and received at least 1 dose of PP6M/PP3M. Here 'N' (number of participants analyzed), included all participants who were evaluable for this outcome measure.

Arm/Group Title	DB PP3M	DB PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	220	473
Positive Subscale Score	-0.1 (2.82)	-0.1 (3.30)
Negative Subscale Score	-0.6 (2.61)	-0.7 (2.70)
General Psychopathology Subscale Score	-0.9 (4.18)	-1.0 (4.86)

19. Secondary Outcome

Title	Number of Participants With Treatment-emergent Clinically Significant Abnormal Laboratory Values in Chemistry During DB Phase
Description	Number of participants with clinically significant abnormal laboratory values in chemistry included alanine aminotransferase (Unit per Litre [U/L]), albumin (Gram per Litre [g/L]), alkaline phosphatase (U/L), aspartate aminotransferase (U/L), bicarbonate (millimoles per litre [mmol/L]), bilirubin (micromoles per litre [umol/L]), calcium (mmol/L), chloride (mmol/L), cholesterol (mmol/L), creatinine (umol/L), gamma glutamyl transferase (GGT) (U/L), glucose (mmol/L), high-density lipoproteins (HDL) cholesterol (mmol/L), low density lipoproteins (LDL) cholesterol (mmol/L), lactate dehydrogenase (U/L), phosphate (mmol/L), potassium (mmol/L), protein (mmol/L), sodium (mmol/L), triglycerides (mmol/L), urate (umol/L), urea nitrogen (mmol/L) were reported. Here, ABL signifies abnormally low and ABH signifies abnormally high levels.
Time Frame	Up to 12 Months of DB Phase

Outcome Measure Data

Analysis Population Description

Double-Blind safety analysis set (DB safety) included all participants who were randomly assigned to treatment group of either PP6M or PP3M during the DB Phase and received at least 1 dose of PP6M/PP3M. Here 'N' (number of participants analyzed), included all participants who were evaluable for this outcome measure. Here 'n' (number analyzed) included all evaluable participants who were analyzed for specified categories.

Arm/Group Title	DB PP3M	DB PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	216	464
Alanine Aminotransferase ABH	0 0%	1 NaN
Albumin ABL	0 0%	0 NaN
Albumin ABH	0 0%	0 NaN
Alkaline Phosphatase ABH	0 0%	0 NaN
Aspartate Aminotransferase ABH	0 0%	0 NaN
Bicarbonate ABL	0 0%	3 NaN
Bicarbonate ABH	0 0%	0 NaN
Bilirubin ABH	0 0%	1 NaN
Calcium ABL	0 0%	0 NaN
Calcium ABH	0 0%	0 NaN
Chloride ABL	4 0.5%	5 NaN
Chloride ABH	0 0%	0 NaN
Cholesterol ABH	2 0.2%	4 NaN
Creatinine ABH	0 0%	0 NaN
Gamma Glutamyl Transferase ABH	0 0%	2 NaN
Glucose ABL	1 0.1%	0 NaN
Glucose ABH	1 0.1%	5 NaN
HDL Cholesterol ABL	18 2.1%	40 NaN
LDL Cholesterol ABL	33 3.9%	44 NaN
LDL Cholesterol ABH	9 1.1%	22 NaN
Lactate Dehydrogenase ABH	0 0%	1 NaN
Phosphate ABL	1 0.1%	8 NaN
Phosphate ABH	0 0%	0 NaN
Potassium ABL	0 0%	0 NaN
Potassium ABH	0 0%	0 NaN
Protein ABL	0 0%	1 NaN
Sodium ABL	1 0.1%	0 NaN
Sodium ABH	0 0%	0 NaN
Triglycerides ABH	4 0.5%	6 NaN
Urate ABL	0 0%	0 NaN
Urate ABH	1 0.1%	4 NaN
Urea Nitrogen ABH	0 0%	0 NaN

20. Secondary Outcome

Title	Number of Participants With Treatment-emergent Clinically Significant Abnormal Laboratory Values in Hematology During DB Phase
Description	Number of participants with clinically significant abnormal laboratory values in hematology included hemoglobin (Hb), hematocrit (Hct), red blood cell (RBC) count, white blood cell (WBC) count with differential, platelets, hemoglobin A1c. Here, ABL signifies abnormally low and ABH signifies abnormally high levels.
Time Frame	Up to 12 Months of DB Phase

Outcome Measure Data

Analysis Population Description

Double-blind safety analysis set (DB safety) included all participants who were randomly assigned to treatment group of either PP6M or PP3M during the DB Phase and received at least 1 dose of PP6M/PP3M. Here 'N' (number of participants analyzed), included all participants who were evaluable for this outcome measure. Here 'n' (number analyzed) included all evaluable participants who were analyzed for specified categories.

Arm/Group Title	DB PP3M	DB PP6M
Arm/Group Description	Participants received 4 doses of PP3M (350 or 525 mg eq.) IM injection for up to 12 months (1 dose every 3 month) during DB phase.	Participants received 2 doses of PP6M (700 or 1000 mg eq.) IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.
Measure Participants	215	459
Basophils ABL	0 0%	0 NaN
Eosinophils ABL	1 0.1%	1 NaN
Erythrocytes ABL	1 0.1%	0 NaN
Erythrocytes ABH	0 0%	0 NaN
Hematocrit ABL	0 0%	1 NaN
Hematocrit ABH	0 0%	0 NaN
Hemoglobin ABL	1 0.1%	0 NaN
Hemoglobin ABH	0 0%	0 NaN
Leukocytes ABL	0 0%	0 NaN
Leukocytes ABH	2 0.2%	4 NaN
Lymphocytes ABL	0 0%	2 NaN
Lymphocytes ABH	1 0.1%	1 NaN
Monocytes ABH	0 0%	0 NaN
Neutrophils ABL	1 0.1%	0 NaN
Neutrophils ABH	0 0%	0 NaN
Platelets ABL	0 0%	0 NaN
Platelets ABH	0 0%	0 NaN

Adverse Events

Time Frame	Up to 2.5 Years
Adverse Event Reporting Description	Open-label (OL) safety set included all participants who received at least 1 dose of OL study drug (excluding the first study participants if re-screened), both transition and maintenance phases. Double-blind (DB) safety set included all participants who were randomly assigned to treatment group either PP6M or PP3M during DB Phase and received at least 1 dose of DB study drug. Participants from DB safety set continued in follow-up phase.
Arm/Group Title	Open-Label (OL) PP1M/PP3M		Double-blind PP3M		Double-blind PP6M		Follow-up (FU) Phase PP3M		Follow-up Phase PP6M
Arm/Group Description	Participants previously treated with oral antipsychotics, or injectable risperidone, or a moderate or higher dose of paliperidone palmitate 1-month (PP1M) with previous initiation but without previous stabilization (where stabilization was defined as at least 3 months of injections with the last 2 doses being the same strength) received 1 to 5 intramuscular (IM) injections of PP1M 50 to 150 milligrams equivalent (mg eq.). Participants received single dose of IM injection of PP1M as 100 or 150 mg eq. or PP3M as 350 or 525 mg eq during the OL-maintenance phase.		Participants received 4 doses of PP3M (350 or 525 mg eq. IM injection for up to 12 months (1 dose every 3 month) during DB phase.		Participants received 2 doses of PP6M (700 or 1000 mg eq. IM injection for 12 months (1 dose every 6 months), during the DB Phase. To maintain blinding, participants received IM injections of matching placebo at the 3-month time points between their 6-month doses of PP6M drug.		Participants who have received at least 1 dose of PP3M (350 or 525 mg eq.) IM injection during double-blind phase but then have relapsed or have met other relevant conditions for withdrawal or discontinuation can participate in the follow-up phase PP3M (350 or 525 mg eq.) IM injection for up to 12 months for evaluating efficacy and safety.		Participants received PP6M (700 or 1000 mg eq.) IM injection for up to 12 months for evaluating efficacy and safety.
All Cause Mortality
	Open-Label (OL) PP1M/PP3M		Double-blind PP3M		Double-blind PP6M		Follow-up (FU) Phase PP3M		Follow-up Phase PP6M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/838 (0.1%)		2/224 (0.9%)		1/478 (0.2%)		0/42 (0%)		0/109 (0%)
Serious Adverse Events
	Open-Label (OL) PP1M/PP3M		Double-blind PP3M		Double-blind PP6M		Follow-up (FU) Phase PP3M		Follow-up Phase PP6M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/838 (2.7%)		15/224 (6.7%)		24/478 (5%)		1/42 (2.4%)		6/109 (5.5%)
Cardiac disorders
Atrial Fibrillation	1/838 (0.1%)		0/224 (0%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Gastrointestinal disorders
Intestinal Obstruction	0/838 (0%)		0/224 (0%)		1/478 (0.2%)		0/42 (0%)		0/109 (0%)
General disorders
Death	0/838 (0%)		0/224 (0%)		1/478 (0.2%)		0/42 (0%)		0/109 (0%)
Sudden Death	0/838 (0%)		1/224 (0.4%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Hepatobiliary disorders
Cholelithiasis	0/838 (0%)		1/224 (0.4%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Infections and infestations
Furuncle	1/838 (0.1%)		0/224 (0%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Pneumonia	1/838 (0.1%)		0/224 (0%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Injury, poisoning and procedural complications
Femur Fracture	0/838 (0%)		1/224 (0.4%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Limb Injury	0/838 (0%)		1/224 (0.4%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Radius Fracture	0/838 (0%)		0/224 (0%)		1/478 (0.2%)		0/42 (0%)		0/109 (0%)
Musculoskeletal and connective tissue disorders
Rotator Cuff Syndrome	1/838 (0.1%)		0/224 (0%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain Neoplasm	0/838 (0%)		0/224 (0%)		0/478 (0%)		0/42 (0%)		1/109 (0.9%)
Chronic Lymphocytic Leukaemia	0/838 (0%)		1/224 (0.4%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Nasal Sinus Cancer	0/838 (0%)		0/224 (0%)		0/478 (0%)		0/42 (0%)		1/109 (0.9%)
Neoplasm Malignant	0/838 (0%)		0/224 (0%)		1/478 (0.2%)		0/42 (0%)		0/109 (0%)
Nervous system disorders
Seizure	0/838 (0%)		0/224 (0%)		1/478 (0.2%)		0/42 (0%)		0/109 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous	0/838 (0%)		0/224 (0%)		1/478 (0.2%)		0/42 (0%)		0/109 (0%)
Psychiatric disorders
Acute Psychosis	1/838 (0.1%)		0/224 (0%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Adjustment Disorder with Mixed Anxiety and Depressed Mood	0/838 (0%)		0/224 (0%)		1/478 (0.2%)		0/42 (0%)		0/109 (0%)
Adjustment Disorder with Mixed Disturbance of Emotion and Conduct	0/838 (0%)		1/224 (0.4%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Alcohol Withdrawal Syndrome	1/838 (0.1%)		0/224 (0%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Behavioural Addiction	1/838 (0.1%)		0/224 (0%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Completed Suicide	1/838 (0.1%)		0/224 (0%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Depression	0/838 (0%)		0/224 (0%)		1/478 (0.2%)		0/42 (0%)		0/109 (0%)
Hallucination, Auditory	0/838 (0%)		1/224 (0.4%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Mental Disorder	0/838 (0%)		0/224 (0%)		0/478 (0%)		0/42 (0%)		1/109 (0.9%)
Mixed Anxiety and Depressive Disorder	0/838 (0%)		0/224 (0%)		1/478 (0.2%)		0/42 (0%)		0/109 (0%)
Panic Disorder	0/838 (0%)		0/224 (0%)		1/478 (0.2%)		0/42 (0%)		0/109 (0%)
Psychotic Disorder	3/838 (0.4%)		2/224 (0.9%)		1/478 (0.2%)		0/42 (0%)		0/109 (0%)
Psychotic Symptom	0/838 (0%)		0/224 (0%)		1/478 (0.2%)		0/42 (0%)		0/109 (0%)
Schizophrenia	6/838 (0.7%)		1/224 (0.4%)		8/478 (1.7%)		0/42 (0%)		2/109 (1.8%)
Suicidal Ideation	3/838 (0.4%)		2/224 (0.9%)		1/478 (0.2%)		1/42 (2.4%)		0/109 (0%)
Suicide Attempt	2/838 (0.2%)		0/224 (0%)		2/478 (0.4%)		0/42 (0%)		1/109 (0.9%)
Renal and urinary disorders
Pelvi-Ureteric Obstruction	0/838 (0%)		0/224 (0%)		1/478 (0.2%)		0/42 (0%)		0/109 (0%)
Reproductive system and breast disorders
Priapism	0/838 (0%)		0/224 (0%)		1/478 (0.2%)		0/42 (0%)		0/109 (0%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	0/838 (0%)		1/224 (0.4%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Chronic Obstructive Pulmonary Disease	2/838 (0.2%)		1/224 (0.4%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Dyspnoea	1/838 (0.1%)		0/224 (0%)		1/478 (0.2%)		0/42 (0%)		0/109 (0%)
Pulmonary Embolism	0/838 (0%)		1/224 (0.4%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Surgical and medical procedures
Mammoplasty	0/838 (0%)		1/224 (0.4%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Vascular disorders
Deep Vein Thrombosis	0/838 (0%)		0/224 (0%)		1/478 (0.2%)		0/42 (0%)		0/109 (0%)
Peripheral Artery Occlusion	0/838 (0%)		1/224 (0.4%)		0/478 (0%)		0/42 (0%)		0/109 (0%)
Other (Not Including Serious) Adverse Events
	Open-Label (OL) PP1M/PP3M		Double-blind PP3M		Double-blind PP6M		Follow-up (FU) Phase PP3M		Follow-up Phase PP6M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	127/838 (15.2%)		52/224 (23.2%)		125/478 (26.2%)		1/42 (2.4%)		5/109 (4.6%)
General disorders
Injection Site Pain	72/838 (8.6%)		9/224 (4%)		37/478 (7.7%)		0/42 (0%)		0/109 (0%)
Infections and infestations
Nasopharyngitis	22/838 (2.6%)		13/224 (5.8%)		22/478 (4.6%)		1/42 (2.4%)		4/109 (3.7%)
Upper Respiratory Tract Infection	19/838 (2.3%)		9/224 (4%)		24/478 (5%)		0/42 (0%)		1/109 (0.9%)
Investigations
Weight Increased	8/838 (1%)		17/224 (7.6%)		40/478 (8.4%)		0/42 (0%)		0/109 (0%)
Nervous system disorders
Headache	16/838 (1.9%)		12/224 (5.4%)		32/478 (6.7%)		0/42 (0%)		0/109 (0%)

Limitations/Caveats

The non-inferiority design was based on the principle of enrichment; that is, criteria of clinical stability were applied prior to entry into the Double-blind Phase. Hence, the ITT (DB) analysis set does not reflect the overall sample of participants who were initially enrolled in Study PSY3015 (ClinicalTrials.gov Identifier: NCT03345342) for treatment with PP3M/PP6M. Therefore, results may not reflect true efficacy for prevention of relapses in the overall population.

More Information

Certain Agreements

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

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the Sponsor for review at least 60 days before submission for publication or presentation. Expedited reviews will be arranged for abstracts, poster presentations, or other materials. If requested by the Sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application.