Clinical trial NCT01515423: Study of Paliperidone Palmitate 3 Month and 1 Month Formulations for the Treatment of Patients With Schizophrenia
Official title: A Randomized, Multicenter, Double-Blind, Non-inferiority Study of Paliperidone Palmitate 3 Month and 1 Month Formulations for the Treatment of Subjects With Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Keywords: Schizophrenia
R092670
Paliperidone Palmitate
Paliperidone palmitate 1 month formulation (PP1M)
Paliperidone palmitate 3 month formulation (PP3M)
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2012-01-24
Enrollment: 1429
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to demonstrate that a paliperidone palmitate 3 month formulation (PP3M) is as effective as the paliperidone palmitate 1 month formulation (PP1M) in the treatment of patients with schizophrenia who have been stabilized on PP1M.

Detailed description: This is a randomized (the study drug is assigned by chance), double blind (neither physician nor patient knows the treatment that the patient receives), parallel group (each group of patients will be treated at the same time), multicenter non-inferiority (the effect of the new treatment is not worse than that of the comparison treatment) study. A new formulation of paliperidone palmitate with a 3-month injection interval (PP3M) is being tested for use as maintenance treatment for subjects with schizophrenia who have been first stabilized on paliperidone palmitate with a 1-month injection interval (PP1M). The study consists of 3 phases: a screening/washout/tolerability phase (up to 21 days); a 17-week open-label (all people know the identity of the intervention) stabilization phase (referred to as the Open-label Phase) and a 48-week fixed dose, randomized, double-blind controlled phase (referred to as the Double-blind Phase). After completion of the Screening Phase, all patients will receive PP1M in the Open-label Phase. During this time, flexible dosing will occur at Weeks 5 and 9. At Week 13 patients are to receive the dose of PP1M that was administered at Week 9. Patients who are clinically stable at the end of the Open-label Phase will enter the Double-blind Phase and will be randomly assigned in a 1:1 ratio to receive fixed doses of PP3M or PP1M.

Eligibility criteria: Inclusion Criteria:

* Patients with schizophrenia for more than 1 year and whose symptoms are worsening in the opinion of the investigator
* A total score in the Positive and Negative Syndrome Scale (PANSS) between 70 and 120
* Signed informed consent
* Women must not be pregnant, breastfeeding, and if capable of pregnancy must practice an effective method of birth control
* Men must agree to use a double-barrier method of birth control
* Be medically stable on the basis of clinical laboratory tests, physical examination, medical history, vital signs, and electrocardiogram (ECG)

Exclusion Criteria:

* A diagnosis other than schizophrenia, e.g., dissociative disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, schizophreniform disorder, autistic disorder, primary substance-induced psychotic disorder, dementia-related psychosis
* Relevant history or current presence of any significant or unstable medical condition(s) determined to be clinically significant by the Investigator (ie, obesity, diabetes, heart disease etc)
* A diagnosis of substance dependence within 6 months before screening
* History of neuroleptic malignant syndrome (NMS) or tardive dyskinesia
* Clozapine use in the last 2 months when used for treatment-resistant or treatment-refractory illness
* Clinically significant findings in biochemistry, hematology, ECG or urinalysis results
* Any other disease or condition that, in the opinion of the investigator, would make participation not in the best interest of the patient or that could prevent, limit, or confound the protocol-specified assessments

Primary outcomes:
measure: Percentage of Participants Without Relapse at Week 48 During the Double-Blind Phase
timeFrame: Up to 48 weeks
Secondary outcomes:
measure: Change From Double-Blind (DB) Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 48
timeFrame: DB Baseline (Week 17) and 48 week or DB Endpoint
measure: Change From DB Baseline in Clinical Global Impression Severity (CGI-S) Scale Score at Week 48
timeFrame: DB Baseline (Week 17) and 48 week or DB Endpoint
measure: Change From DB Baseline in Personal and Social Performance (PSP) Total Score at Week 48
timeFrame: DB Baseline (Week 17) and 48 week or DB Endpoint
measure: Percentage of Participants Who Met the Criteria for Symptomatic Remission Based on Andreasen Criteria
timeFrame: Weeks 41 to 65
measure: Change From Baseline in Positive and Negative Syndrome Subscales Score at Week 48
timeFrame: DB Baseline (Week 17) and 48 week or DB Endpoint
measure: Change From Baseline in Marder Factor Subscale Score at Week 48
timeFrame: DB Baseline (Week 17) and 48 week or DB Endpoint
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Glendale
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Oakland
country: United States
state: California
city: Oceanside
country: United States
state: California
city: Orange
country: United States
state: California
city: San Diego
country: United States
state: California
city: New Britain
country: United States
state: Connecticut
city: Bradenton
country: United States
state: Florida
city: Kissimmee
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Wichita
country: United States
state: Kansas
city: East Lansing
country: United States
state: Michigan
city: St. Louis
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: Jamaica
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Canton
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Philadelphia
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Memphis
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Bothell
country: United States
state: Washington
city: Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: Córdoba
country: Argentina
city: Rosario
country: Argentina
city: Elizabeth Vale
country: Australia
city: Frankston
country: Australia
city: Innsbruck
country: Austria
city: Assebroek
country: Belgium
city: Bertrix
country: Belgium
city: Brussel - Jette
country: Belgium
city: Dave
country: Belgium
city: Heusden
country: Belgium
city: Marchienne-Au-Pont
country: Belgium
city: Sint-Denijs-Westrem
country: Belgium
city: Rio De Janeiro
country: Brazil
city: Bourgas N/A
country: Bulgaria
city: Kazanlak
country: Bulgaria
city: Radnevo
country: Bulgaria
city: Sofia
country: Bulgaria
city: Calgary
country: Canada
state: Alberta
city: Halifax
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Burlington
country: Canada
city: Baoding
country: China
city: Beijing
country: China
city: Changsha
country: China
city: Guangdong
country: China
city: Guangzhou
country: China
city: Hangzhou
country: China
city: Kunming
country: China
city: Shanghai
country: China
city: Tianjin
country: China
city: Wuhan
country: China
city: Xi'An
country: China
city: Brno
country: Czech Republic
city: Horovice
country: Czech Republic
city: Liberec
country: Czech Republic
city: Praha 10
country: Czech Republic
city: Praha 9
country: Czech Republic
city: Prerov
country: Czech Republic
city: Clermont Ferrand
country: France
city: Dole
country: France
city: Montpellier
country: France
city: Toulon
country: France
city: Bochum
country: Germany
city: Gelsenkirchen
country: Germany
city: Hamburg
country: Germany
city: Heidelberg
country: Germany
city: München
country: Germany
city: Arta
country: Greece
city: Athens
country: Greece
city: Katerini
country: Greece
city: Balassagyarmat N/A
country: Hungary
city: Budapest
country: Hungary
city: Gyõr
country: Hungary
city: Kalocsa
country: Hungary
city: Sopron
country: Hungary
city: Aizuwakamatsu
country: Japan
city: Fujioka
country: Japan
city: Fujisawa
country: Japan
city: Hadano
country: Japan
city: Himeji
country: Japan
city: Hitachi
country: Japan
city: Ichikawa
country: Japan
city: Kanuma
country: Japan
city: Kanzaki
country: Japan
city: Kashihara
country: Japan
city: Kashiwara
country: Japan
city: Kasuya
country: Japan
city: Kawasaki
country: Japan
city: Kitagunma
country: Japan
city: Kochi
country: Japan
city: Kodaira
country: Japan
city: Kumagaya
country: Japan
city: Kumamoto
country: Japan
city: Kure
country: Japan
city: Matsusaka
country: Japan
city: Mitaka
country: Japan
city: Moriguchi
country: Japan
city: Nagasaki
country: Japan
city: Naha
country: Japan
city: Nirasaki
country: Japan
city: Ohta
country: Japan
city: Okayama
country: Japan
city: Okinawa
country: Japan
city: Sakai
country: Japan
city: Shibukawa
country: Japan
city: Takatsuki
country: Japan
city: Toki
country: Japan
city: Tokushima
country: Japan
city: Tokyo
country: Japan
city: Toyoake
country: Japan
city: Ueda
country: Japan
city: Yatsushiro
country: Japan
city: Yokkaichi
country: Japan
city: Yokohama
country: Japan
city: Busan
country: Korea, Republic of
city: Gwangju-Si
country: Korea, Republic of
city: Gyeonggi-Do
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Guadalajara
country: Mexico
city: Monterrey
country: Mexico
city: Tlalnepantla
country: Mexico
city: Belchatow
country: Poland
city: Bydgoszcz
country: Poland
city: Chelmno
country: Poland
city: Gdynia Na
country: Poland
city: Lubin
country: Poland
city: Lubliniec
country: Poland
city: Piekary Slaskie
country: Poland
city: Torun N/A
country: Poland
city: Zabki
country: Poland
city: Almada N/A
country: Portugal
city: Angra Do Heroísmo
country: Portugal
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Brasov
country: Romania
city: Cluj-Napoca
country: Romania
city: Arkhangelsk
country: Russian Federation
city: Ekaterinburg
country: Russian Federation
city: Gatchina
country: Russian Federation
city: Krasnodar N/A
country: Russian Federation
city: Moscow N/A
country: Russian Federation
city: Nizhniy Novgorod
country: Russian Federation
city: Saratov
country: Russian Federation
city: Smolensk Region N/A
country: Russian Federation
city: Smolensk
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: St-Peterburg
country: Russian Federation
city: St-Petersburg
country: Russian Federation
city: Tomsk Na
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Bratislava
country: Slovakia
city: Michalovce
country: Slovakia
city: Rimavska Sobota
country: Slovakia
city: Trencin
country: Slovakia
city: Alicante
country: Spain
city: Baracaldo
country: Spain
city: Barcelona
country: Spain
city: Coslada
country: Spain
city: Elche
country: Spain
city: Madrid
country: Spain
city: Zamora
country: Spain
city: Uppsala
country: Sweden
city: Bali Township, Taipei County
country: Taiwan
city: Kaohsiung
country: Taiwan
city: Taoyuan
country: Taiwan
city: Glevakha
country: Ukraine
city: Kharkov
country: Ukraine
city: Kiev
country: Ukraine
city: Odessa
country: Ukraine
city: Poltava
country: Ukraine
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Gopal S, Gogate J, Pungor K, Kim E, Singh A, Mathews M. Improvement of Negative Symptoms in Schizophrenia with Paliperidone Palmitate 1-Month and 3-Month Long-Acting Injectables: Results from a Phase 3 Non-Inferiority Study. Neuropsychiatr Dis Treat. 2020 Mar 6;16:681-690. doi: 10.2147/NDT.S226296. eCollection 2020.
citation: Savitz AJ, Xu H, Gopal S, Nuamah I, Mathews M, Soares B. Efficacy and safety of paliperidone palmitate 3-month formulation in Latin American patients with schizophrenia: A subgroup analysis of data from two large phase 3 randomized, double-blind studies. Braz J Psychiatry. 2019 Nov-Dec;41(6):499-510. doi: 10.1590/1516-4446-2018-0153.
citation: Nash AI, Turkoz I, Savitz AJ, Mathews M, Kim E. Predictors of achieving remission in schizophrenia patients treated with paliperidone palmitate 3-month formulation. Neuropsychiatr Dis Treat. 2019 Mar 22;15:731-737. doi: 10.2147/NDT.S194264. eCollection 2019.
citation: Mathews M, Pei H, Savitz A, Nuamah I, Hough D, Alphs L, Gopal S. Paliperidone Palmitate 3-Monthly Versus 1-Monthly Injectable in Patients With Schizophrenia With or Without Prior Exposure to Oral Risperidone or Paliperidone: A Post Hoc, Subgroup Analysis. Clin Drug Investig. 2018 Aug;38(8):695-702. doi: 10.1007/s40261-018-0647-z.
citation: Magnusson MO, Samtani MN, Plan EL, Jonsson EN, Rossenu S, Vermeulen A, Russu A. Population Pharmacokinetics of a Novel Once-Every 3 Months Intramuscular Formulation of Paliperidone Palmitate in Patients with Schizophrenia. Clin Pharmacokinet. 2017 Apr;56(4):421-433. doi: 10.1007/s40262-016-0459-3.
citation: Samtani MN, Nandy P, Ravenstijn P, Remmerie B, Vermeulen A, Russu A, D'hoore P, Baum EZ, Savitz A, Gopal S, Hough D. Prospective dose selection and acceleration of paliperidone palmitate 3-month formulation development using a pharmacometric bridging strategy. Br J Clin Pharmacol. 2016 Nov;82(5):1364-1370. doi: 10.1111/bcp.13050. Epub 2016 Jul 24.