Study of Paliperidone Palmitate 3 Month and 1 Month Formulations for the Treatment of Patients With Schizophrenia

NCT ID: NCT01515423

Last Updated: 2016-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1429 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2015-03-31

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.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Paliperidone palmitate 3-month (PP3M)

A formulation of paliperidone palmitate with a 3-month injection interval

Group Type: EXPERIMENTAL

PP3M 175 mg eq.

Intervention Type: DRUG

Type= exact number, unit= mg eq., number= 175, form= injection, route= intramuscular use. One injection every third month for 48 weeks.

PP3M 263 mg eq.

Intervention Type: DRUG

Type= exact number, unit= mg eq., number= 263, form= injection, route= intramuscular use. One injection every third month for 48 weeks.

PP3M 350 mg eq.

Intervention Type: DRUG

Type= exact number, unit= mg eq., number= 350, form= injection, route= intramuscular use. One injection every third month for 48 weeks.

PP3M 525 mg eq.

Intervention Type: DRUG

Type= exact number, unit= mg eq., number= 525, form= injection, route= intramuscular use. One injection every third month for 48 weeks.

Placebo (20% Intralipid)

Intervention Type: DRUG

Form= injection, route= intramuscular use. One injection monthly when not receiving active medication for 48 weeks.

Paliperidone palmitate 1-month (PP1M)

A formulation of paliperidone palmitate with a 1-month injection interval

Group Type: ACTIVE_COMPARATOR

PP1M 50 mg eq.

Intervention Type: DRUG

Type= exact number, unit= mg eq., number= 50, form= injection, route= intramuscular use. One injection every month for 48 weeks.

PP1M 75 mg eq.

Intervention Type: DRUG

Type= exact number, unit= mg eq., number= 75, form= injection, route= intramuscular use. One injection every month for 48 weeks.

PP1M 100 mg eq.

Intervention Type: DRUG

Type= exact number, unit= mg eq., number= 100, form= injection, route= intramuscular use. One injection every month for 48 weeks.

PP1M 150 mg eq.

Intervention Type: DRUG

Type= exact number, unit= mg eq., number= 150, form= injection, route= intramuscular use. One injection every month for 48 weeks.

Interventions

PP3M 175 mg eq.

Type= exact number, unit= mg eq., number= 175, form= injection, route= intramuscular use. One injection every third month for 48 weeks.

Intervention Type: DRUG

PP3M 263 mg eq.

Type= exact number, unit= mg eq., number= 263, form= injection, route= intramuscular use. One injection every third month for 48 weeks.

Intervention Type: DRUG

PP3M 350 mg eq.

Type= exact number, unit= mg eq., number= 350, form= injection, route= intramuscular use. One injection every third month for 48 weeks.

Intervention Type: DRUG

PP3M 525 mg eq.

Type= exact number, unit= mg eq., number= 525, form= injection, route= intramuscular use. One injection every third month for 48 weeks.

Intervention Type: DRUG

Placebo (20% Intralipid)

Form= injection, route= intramuscular use. One injection monthly when not receiving active medication for 48 weeks.

Intervention Type: DRUG

PP1M 50 mg eq.

Type= exact number, unit= mg eq., number= 50, form= injection, route= intramuscular use. One injection every month for 48 weeks.

Intervention Type: DRUG

PP1M 75 mg eq.

Type= exact number, unit= mg eq., number= 75, form= injection, route= intramuscular use. One injection every month for 48 weeks.

Intervention Type: DRUG

PP1M 100 mg eq.

Type= exact number, unit= mg eq., number= 100, form= injection, route= intramuscular use. One injection every month for 48 weeks.

Intervention Type: DRUG

PP1M 150 mg eq.

Type= exact number, unit= mg eq., number= 150, form= injection, route= intramuscular use. One injection every month for 48 weeks.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Little Rock, Arkansas, United States

Glendale, California, United States

Long Beach, California, United States

Oakland, California, United States

Oceanside, California, United States

Orange, California, United States

San Diego, California, United States

New Britain, Connecticut, United States

Bradenton, Florida, United States

Kissimmee, Florida, United States

Tampa, Florida, United States

Wichita, Kansas, United States

East Lansing, Michigan, United States

St Louis, Missouri, United States

Las Vegas, Nevada, United States

Jamaica, New York, United States

Durham, North Carolina, United States

Canton, Ohio, United States

Oklahoma City, Oklahoma, United States

Philadelphia, Pennsylvania, United States

Charleston, South Carolina, United States

Memphis, Tennessee, United States

Austin, Texas, United States

Bothell, Washington, United States

Buenos Aires, , Argentina

Córdoba, , Argentina

Rosario, , Argentina

Elizabeth Vale, , Australia

Frankston, , Australia

Innsbruck, , Austria

Assebroek, , Belgium

Bertrix, , Belgium

Dave, , Belgium

Heusden, , Belgium

Jette, , Belgium

Marchienne-au-Pont, , Belgium

Sint-Denijs-Westrem, , Belgium

Rio de Janeiro, , Brazil

Burgas, , Bulgaria

Kazanlak, , Bulgaria

Radnevo, , Bulgaria

Sofia, , Bulgaria

Calgary, Alberta, Canada

Halifax, Ontario, Canada

Montreal, Quebec, Canada

Burlington, , Canada

Baoding, , China

Beijing, , China

Changsha, , China

Guangdong, , China

Guangzhou, , China

Hangzhou, , China

Kunming, , China

Shanghai, , China

Tianjin, , China

Wuhan, , China

Xi'an, , China

Brno, , Czechia

Hořovice, , Czechia

Liberec, , Czechia

Prague, , Czechia

Přerov, , Czechia

Clermont-Ferrand, , France

Dole, , France

Montpellier, , France

Toulon, , France

Bochum, , Germany

Gelsenkirchen, , Germany

Hamburg, , Germany

Heidelberg, , Germany

München, , Germany

Arta, , Greece

Athens, , Greece

Katerini, , Greece

Balassagyarmat, , Hungary

Budapest, , Hungary

Gyõr, , Hungary

Kalocsa, , Hungary

Sopron, , Hungary

Aizu-Wakamatsu, , Japan

Fujioka, , Japan

Fujisawa, , Japan

Hadano, , Japan

Himeji, , Japan

Hitachi, , Japan

Ichikawa, , Japan

Kanuma, , Japan

Kanzaki, , Japan

Kashihara, , Japan

Kashiwara, , Japan

Kasuya, , Japan

Kawasaki, , Japan

Kitagunma, , Japan

Kochi, , Japan

Kodaira, , Japan

Kumagaya, , Japan

Kumamoto, , Japan

Kure, , Japan

Matsusaka, , Japan

Mitaka, , Japan

Moriguchi, , Japan

Nagasaki, , Japan

Naha, , Japan

Nirasaki, , Japan

Ohta, , Japan

Okayama, , Japan

Okinawa, , Japan

Sakai, , Japan

Shibukawa, , Japan

Takatsuki, , Japan

Toki, , Japan

Tokushima, , Japan

Tokyo, , Japan

Toyoake, , Japan

Ueda, , Japan

Yatsushiro, , Japan

Yokkaichi, , Japan

Yokohama, , Japan

Guadalajara, , Mexico

Monterrey, , Mexico

Tlalnepantla, , Mexico

Bełchatów, , Poland

Bydgoszcz, , Poland

Chełmno, , Poland

Gdynia Na, , Poland

Lubin, , Poland

Lubliniec, , Poland

Piekary Śląskie, , Poland

Torun, , Poland

Ząbki, , Poland

Almada, , Portugal

Angra do Heroísmo, , Portugal

Coimbra, , Portugal

Lisbon, , Portugal

Porto, , Portugal

Brasov, , Romania

Cluj-Napoca, , Romania

Arkhangelsk, , Russia

Gatchina, , Russia

Krasnodar, , Russia

Moscow, , Russia

Nizhny Novgorod, , Russia

Saint Petersburg, , Russia

Saratov, , Russia

Smolensk, , Russia

Smolensk Region N/A, , Russia

St-Peterburg, , Russia

Tomsk Na, , Russia

Yaroslavl, , Russia

Yekaterinburg, , Russia

Bratislava, , Slovakia

Michalovce, , Slovakia

Rimavská Sobota, , Slovakia

Trenčín, , Slovakia

Busan, , South Korea

Gwangju, , South Korea

Gyeonggi-do, , South Korea

Seoul, , South Korea

Alicante, , Spain

Barakaldo, , Spain

Barcelona, , Spain

Coslada, , Spain

Elche, , Spain

Madrid, , Spain

Zamora, , Spain

Uppsala, , Sweden

Bali Township, Taipei County, , Taiwan

Kaohsiung City, , Taiwan

Taoyuan District, , Taiwan

Hlevakha, , Ukraine

Kharkiv, , Ukraine

Kiev, , Ukraine

Odesa, , Ukraine

Poltava, , Ukraine

Countries

United States; Argentina; Australia; Austria; Belgium; Brazil; Bulgaria; Canada; China; Czechia; France; Germany; Greece; Hungary; Japan; Mexico; Poland; Portugal; Romania; Russia; Slovakia; South Korea; Spain; Sweden; Taiwan; Ukraine

References

Li X, Ye C, Zhang W, Jia M, Wang G. Factors Associated with Symptom Stabilization that Allow for Successful Transition from Once-Monthly Paliperidone Palmitate to Three-Monthly Paliperidone Palmitate: A Post Hoc Analysis Examined Clinical Characteristics in Chinese Patients with Schizophrenia. CNS Drugs. 2024 Jan;38(1):55-65. doi: 10.1007/s40263-023-01056-x. Epub 2024 Jan 8.

Reference Type: DERIVED

PMID: 38190077 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32184607 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30994855 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30962688 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29882073 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27743205 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27333588 (View on PubMed)

Other Identifiers

R092670PSY3011

Identifier Type: OTHER

Identifier Source: secondary_id

2011-004889-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1135-7054

Identifier Type: OTHER

Identifier Source: secondary_id

CR100662

Identifier Type: -

Identifier Source: org_study_id