A Study of Paliperidone Palmitate 6-Month Formulation

Schizophrenia Clinical Trial

Official title:

A Double-blind, Randomized, Active-controlled, Parallel-group Study of Paliperidone Palmitate 6-Month Formulation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03345342
• Other study ID #: CR108390
• Secondary ID: R092670PSY301520
• Status: Completed
• Phase: Phase 3
• Start date: November 20, 2017
• Est. completion date: May 8, 2020

Study information

• Verified date: September 2023
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 841
• Est. completion date: May 8, 2020
• Est. primary completion date: May 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• PP6M
Participants will receive intramuscular injection of PP6M.
• PP3M 350 mg eq.
Participants will receive intramuscular injection of PP3M 350 mg eq.
• PP3M 525 mg eq.
Participants will receive intramuscular injection of PP3M 525 mg eq.
• PP1M
Participants will receive intramuscular injection of PP1M 50 to 150 mg eq.

Other:
• Placebo
Participants will receive matching placebo.

Locations

Country	Name	City	State
Argentina	Fundacion para el Estudio y Tratamiento de las Enfermedades Mentales	Ciudad Autónoma De Buenos Aires
Argentina	CEN	Cordoba
Argentina	Sanatorio Prof. Leon S. Morra	Cordoba
Argentina	Clinica Privada de Salud Mental Santa Teresa de Ávila	La Plata
Argentina	Instituto de Neurociencias San Agustín	La Plata
Argentina	C.I.A.P. (Centro de investigación y Asistencia en Psiquiatría)	Rosario
Australia	The Lyell McEwin Hospital	Elizabeth Vale
Australia	Neuro Trials Victoria	Noble Park
Brazil	Trial Tech Tecnologia em Pesquisas com Medicamentos	Curitiba
Brazil	Instituto Bairral de Psiquiatria	Itapira
Brazil	Hospital das Clinicas de Porto Alegre	Porto Alegre
Brazil	Ruschel Medicina e Pesquisa Clínica Ltda	Rio de Janeiro
Brazil	SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo	Sao Paulo
Brazil	CPQuali Pesquisa Clinica LTDA ME	São Paulo
Brazil	Hospital Das Clinicas Da Faculdade De Medicina Da USP	São Paulo
Bulgaria	Mental Health Center Prof. Dr. Ivan Temkov	Bourgas
Bulgaria	State Psychiatric Hospital Pazardzhik	Pazardzhik
Bulgaria	UMHAT 'Sveti Georgi'-Plovdiv	Plovdiv
Bulgaria	State Psychiatric HospitalDr.Georgi Kissiov	Radnevo
Bulgaria	Centre for Mental Health Prof.N.Shipkovenski EOOD	Sofia
Bulgaria	Medical Center Intermedica, OOD	Sofia
Czechia	Psychiatricka ambulance, MUDr. Marta Holanova	Brno
Czechia	NeuropsychiatrieHK, s.r.o.	Hradec Kralove-Vekose
Czechia	A-Shine s.r.o.	Plzen
Czechia	Institut Neuropsychiatricke pece	Prague
Czechia	Psychiatricka ambulance MUDr. Simona Papezova	Prague
Czechia	PRAGTIS s.r.o.	Praha 2
France	C.H.S. Charles Perrens	Bordeaux
France	CHRU La Colombière	Montpellier
France	CHU Caremeau	Nimes Cedex 9
France	Hopital Sainte Anne	Paris
France	Hôpital Sainte Musse	Toulon Cedex
Hong Kong	Kwai Chung Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Hungary	Józsefvarosi Szent Kozma Egészségügyi Központ	Budapest
Hungary	Petz Aladar Megyei Oktato Korhaz	Gyor
Hungary	Bács-Kiskun Megyei Kórház a Szegedi Tudományegyetem Általános Orvostudományi Kar Oktató Kórháza	Kalocsa
Hungary	CRU Hungary Kft.	Miskolc
India	Ratandeep Multispeciality Hospital	Ahmedabad
India	Sri Ramachandra Medical Centre	Chennai
India	Asha hospital	Hyderabad
India	Ahana Hospitals	Madurai
India	Vinaya Hospital and Research Center	Mangalore
India	Kasturba Medical College Hospital	Manipal
India	Jehangir Clinical Development Center Pvt Ltd	Pune
India	Deva Institute of Health Care and Research Pvt Ltd	Varanasi
Italy	Clinica Psichiatrica - Università di Cagliari	Cagliari
Italy	Dipartimento di Salute Mentale	Lecce
Italy	Seconda Universita degli Studi di Napoli - Azienda Ospedaliera Universitaria	Napoli
Italy	Universita degli Studi di Roma 'La Sapienza' - Azienda Ospedaliera Sant Andrea	Roma
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	CHA Bundang Medical Center, CHA University	Gyeonggi-do
Korea, Republic of	Chonbuk National Univ Hospital	Jeonju
Korea, Republic of	Seoul National University Hospital	Seoul
Malaysia	Hospital Bahagia Ulu Kinta	Ipoh
Malaysia	Hospital Kuala Lumpur	Kuala Lumpur
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Sarawak General Hospital	Kuching
Mexico	Gabipros SC.	Mexico City
Mexico	Centro de Estudios Clinicos y Especialidades Medicas, S.C.	Monterrey
Mexico	Infosame/Research	Monterrey
Mexico	Instituto Neuropsique	Monterrey
Mexico	Centro de Atencion e Investigacion Cardiovascular del Potosi, S.C.	San Luis Potosí
Poland	Mlynowamed Specjalistyczny Psychiatryczny Gabinet Lekarski Joanna Lazarczyk	Bialystok
Poland	Wlokiennicza MED Specjalistyczna Praktyka Lekarska dr n.med. Tomasz Markowski	Bialystok
Poland	Zespol Opieki Zdrowotnej w Chelmnie	Chelmno
Poland	Centrum Badan Klinicznych PI-House sp. z o.o.	Gdansk
Poland	Szpital Specjalistyczny im. H. Klimontowicza, Oddzial Psychiatryczny	Gorlice
Poland	Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS	Leszno
Poland	Centrum Medyczne Luxmed Sp z o o	Lublin
Poland	Poradnia Zdrowia Psychicznego 'Syntonia' w Pruszczu Gdanskim	Pruszcz Gdanski
Poland	Mazowieckie Specjalistyczne Centrum Zdrowia im. Prof. Jana Mazurkiewicza w Pruszkowie	Pruszkow
Poland	Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu	Torun
Russian Federation	Sverdlovsk Regional Clinical Psychiatric Hospital	Ekaterinburg
Russian Federation	Clinical Psychiatric Hospital #3 Named After V.A. Gilyarovsky	Moscow
Russian Federation	Psychiatric Clinical hospital 1 named after N.A. Alekseev	Moscow
Russian Federation	Nizny Novgorod clinical psychiatric hospital 1	Nizny Novgorod
Russian Federation	Saratov Regional Psychiatric hospital named after St. Sofia	Saratov
Russian Federation	SHI 'Saratov City Clinical Hospital 2 n.a V.I. Razumovsky	Saratov
Russian Federation	Psychoneurological dispensary 1	St-Petersburg
Russian Federation	Psychoneurological dispensary 10	St-Petersburg
Russian Federation	Psychoneurological Dispensary of Frunzensky District	St-Petersburg
Russian Federation	St-Petersburg Bekhterev Psychoneurological Research Institute	St-Petersburg
Russian Federation	Psychoneurological Dispensary #4	St.Peterburg
Russian Federation	Research Institute of Mental Health	Tomsk
South Africa	Flexivest 14 Research	Cape Town
South Africa	Gert Bosch - Pretoria South Africa	Pretoria
South Africa	Juan Schrönen - Western Cape South Africa	Welgemoed
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Inst. Internac. Neurociencias Aplicadas	Barcelona
Spain	Hosp. Univ. de Basurto	Bilbao
Spain	Centro Salud Mental La Corredoria	Oviedo
Spain	Hosp. El Bierzo	Ponferrada
Spain	Hosp. Clinico Univ. de Valencia	Valencia
Spain	Hosp. Prov. de Zamora	Zamora
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Mackay Memorial Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital	Taoyuan
Turkey	Abdurrah Yurtarslan Training and Research Hospital	Ankara
Turkey	Ankara Numune Research and Training Hospital	Ankara
Turkey	Erenkoy Mental Health Hospital	Istanbul
Turkey	Selcuk University, Medical School, Department of Psychiatry	Konya
Turkey	Sakarya University Medical Faculty Psychiatry Department	Sakarya
Ukraine	MNCE of Kyiv RC Regional Psychiatric and Narcological Medical Association	Glevakha
Ukraine	Mnpe of Kharkiv Regional Council 'Regional Clinical Psychiatric Hospital #3'	Kharkiv
Ukraine	CNPE'Kherson Regional Institution of Mental Care'of Kherson Regional Council	Kherson
Ukraine	Kyiv Territorial Medical Incorporation 'Psychiatry'	Kyiv
Ukraine	CNCE of the Lviv Regional Council 'Lviv Regional Clinical Psychiatric Hospital'	Lviv
Ukraine	Municipal Institution 'Lviv Regional Clinical Psycho-Neurological Dispensary'	Lviv
Ukraine	CNCE Odesa regional psychiatric hospital #2 Odesa regional council	Oleksandrivka
Ukraine	CNCE 'Cherkasy Regional Psychiatric Hospital of Cherkasy Regional Council'	Smila
Ukraine	CNCE 'Vinnytsya RC Psychoneurological Hospital n.a. O.I. Yushchenko Vinnytsya RC'	Vinnytsia
United States	California Pharmaceutical Research Institute, Inc.	Anaheim	California
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Uptown Research Institute	Chicago	Illinois
United States	Wexner Medical Center at the Ohio State University	Columbus	Ohio
United States	ATP Clinical Research	Costa Mesa	California
United States	Future Search Trials of Dallas	Dallas	Texas
United States	Midwest Clinical Research Center	Dayton	Ohio
United States	Collaborative NeuroScience Network	Garden Grove	California
United States	The Zucker Hillside Hospital	Glen Oaks	New York
United States	Cherry Street Services, Inc.	Grand Rapids	Michigan
United States	New Life Medical Research Center, Inc.	Hialeah	Florida
United States	Clinical Trials of America Inc	Hickory	North Carolina
United States	Alexian Behavioral Health Hospital	Hoffman Estates	Illinois
United States	Synergy East	Lemon Grove	California
United States	Clintex Research Group	Miami	Florida
United States	Florida Research Center Inc.	Miami	Florida
United States	Pacific Research Partners	Oakland	California
United States	University of Pennsylvania Medical Center	Philadelphia	Pennsylvania
United States	Woodland Research Northwest	Rogers	Arkansas
United States	St. Louis Clinical Trials	Saint Louis	Missouri
United States	Psychiatric and Behavioral Solutions	Salt Lake City	Utah
United States	SF-Care, Inc	San Rafael	California
United States	Olympian Clinical Research	Tampa	Florida
United States	Ascension via Christi Research	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Bulgaria,  Czechia,  France,  Hong Kong,  Hungary,  India,  Italy,  Korea, Republic of,  Malaysia,  Mexico,  Poland,  Russian Federation,  South Africa,  Spain,  Taiwan,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Relapse During the Double-Blind (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.	Up to 12 months of DB Phase
Secondary	Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score	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).	Baseline (DB) to 12 Months of DB Phase
Secondary	Change From Baseline in the Clinical Global Impression - Severity (CGI-S) Score	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.	Baseline (DB) to 12 Months of DB Phase
Secondary	Change From Baseline in the Personal and Social Performance (PSP) Scale Total Score	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.	Baseline (DB) to 12 Months of DB Phase
Secondary	Percentage of Participants With Symptomatic Remission Based on PANSS Score During 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.	Up to 12 months of DB Phase
Secondary	Change From Baseline in the Satisfaction With Participants in Social Roles (SPSR) Score	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.	Baseline (DB) to 12 Months of DB Phase
Secondary	Change From Baseline in the Treatment Satisfaction Questionnaire for Medication (TSQM-9) Total Score	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.	Baseline (DB) to 12 Months of DB Phase
Secondary	Change From Baseline in the Simpson-Angus Rating Scale (SAS) Total Score	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.	Baseline (DB) to 12 Months of DB Phase
Secondary	Number of Participants With Symptoms of Akathisia Assessed Using Barnes Akathisia Rating Scale (BARS) Score	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).	Up to 12 Months of DB Phase
Secondary	Change From Baseline in the Abnormal Involuntary Movement Scale (AIMS) Total Score	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.	Baseline (DB) to 12 Months of DB Phase
Secondary	Number of Participants Based on Columbia Suicide Severity Rating Scale (C-SSRS) Total Score	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.	Baseline and endpoint (12 Months of DB Phase)
Secondary	Number of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values During 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).	Baseline (DB) to 12 Months of DB Phase
Secondary	Change From Baseline in the Body Mass Index (BMI) During DB Phase	Change from baseline in BMI was reported.	Baseline (DB) to 12 Months of DB Phase
Secondary	Change From Baseline in the Waist Circumference During DB Phase	Change from baseline in waist circumference was reported.	Baseline (DB) to 12 Months of DB Phase
Secondary	Change From Baseline in the Body Weight During DB Phase	Change from baseline in body weight was reported.	Baseline (DB) to 12 Months of DB Phase
Secondary	Change From Baseline in the Vital Signs (Pulse Rate) During DB Phase	Change from baseline vital signs (pulse rate) were reported. This included supine pulse rate, standing pulse rate and supine-standing pulse rate.	Baseline (DB) to 12 Months of DB Phase
Secondary	Change From Baseline in the Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) During DB Phase	Change from baseline in vital signs including SBP and DBP (supine/standing) were reported.	Baseline (DB) to 12 Months of DB Phase
Secondary	Change From Baseline in Positive and Syndrome Scale (PANSS) Subscales Score During 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).	Baseline (DB) to 12 Months of DB Phase
Secondary	Number of Participants With Treatment-emergent Clinically Significant Abnormal Laboratory Values in Chemistry During 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.	Up to 12 Months of DB Phase
Secondary	Number of Participants With Treatment-emergent Clinically Significant Abnormal Laboratory Values in Hematology During 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.	Up to 12 Months of DB Phase