Clinical trial NCT01281527: Paliperidone Palmitate Flexible Dosing in Schizophrenia
Official title: A 6-month, Open Label, Prospective, Multicenter, International, Exploratory Study of a Transition to Flexibly Dosed Paliperidone Palmitate in Patients With Schizophrenia Previously Unsuccessfully Treated With Oral or Long-acting Injectable Antipsychotics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Keywords: Paliperidone palmitate
Schizophrenia
Intramuscular injection
Lead sponsor: Janssen-Cilag International NV
Sponsor class: INDUSTRY
First posted: 2011-01-24
Enrollment: 1044
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study explores the tolerability, safety and efficacy (i.e. how well the drug works) of flexibly dosed paliperidone palmitate in the treatment of schizophrenia in patients previously unsuccessfully treated with other oral or long-acting injectable (LAI) (i.e. with a long duration of action) antipsychotics.

Detailed description: This study explores the tolerability, safety and treatment response of flexibly dosed paliperidone palmitate in approximately 1,000 patients with schizophrenia previously unsuccessfully treated with an oral or LAI antipsychotic medication. Non-acute and acute patients will be involved in the study. This study consists of a screening phase, a 6-month core treatment phase, and an optional extension phase. A transition period of preferably a maximum of 4 weeks will be allowed for the previous oral antipsychotic. When switching patients from previous LAI antipsychotics, paliperidone palmitate will be initiated in place of the next scheduled injection. Patients without source documentation of previous risperidone or paliperidone exposure must undergo oral tolerability testing with paliperidone ER (3 mg/day) for the 2 days prior to Baseline Visit. Patients who successfully complete the 6-month core treatment phase and would like to continue treatment with paliperidone palmitate may be enrolled in an optional extension phase until paliperidone palmitate is available in their respective country or until a maximum duration of 12 months after the last subject has completed the 6-month core treatment phase, whichever comes first. Patients will receive, without cost, paliperidone palmitate. Patients entering this optional extension phase, will receive once monthly injections with paliperidone palmitate. The recommended maintenance dose for these monthly injections is 75 mg eq. once monthly but flexible dosing in the range of 50 to 150 mg eq. once monthly will be allowed. The doctor may flexibly increase or decrease the dose preferably by one dosing level (within the range of 50 to 150 mg eq.) according to patients' clinical needs. During the extension phase, two types of visits can be distinguished: 'assessment visits' and 'treatment-only visits'. At each assessment visit (once every 3 months +/- 7 days), patients will receive their injection and will be questioned about adverse events (AEs). Body weight will also be assessed. Paliperidone palmitate will be given once monthly by injection in either the upper arm or buttocks muscle, but start every time with upper arm application. The recommended maintenance dose for these monthly injections is 75 mg eq., range could be between 50 to 150 mg eq.

Eligibility criteria: Inclusion Criteria:

Meet the DSM-IV criteria for schizophrenia Currently non-acute, i.e., on the same antipsychotic medication used for the treatment of schizophrenia given in an adequate dose and a CGI-S change \<= 1 in the past 4 weeks before enrollment Patient has been given an adequate dose of either an appropriate oral antipsychotic, or a protocol-defined LAI antipsychotic for an adequate period of time prior to enrollment, but current treatment is considered unsuccessful OR Patients with acute symptoms of schizophrenia, previously treated with an oral antipsychotic, having a baseline total Positive and Negative Syndrome Scale (PANSS) score \>= 80 and a baseline CGI-S score \>= 4 Women must be postmenopausal for at least 1 year, surgically sterile, abstinent (at the discretion of the investigator/per local regulations), or if sexually active, be practicing a highly effective method of birth control as local regulations permit, and before entry, must agree to continue to use the same method of contraception throughout the study Is cooperative and reliable, and agrees to receive regular injections and complete all aspects of the protocol Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug.

Exclusion Criteria:

The patient's psychiatric diagnosis is due to direct pharmacological effects of a substance (e.g., a drug of abuse or medication) or a general medical condition (e.g., clinically notable hypothyroidism) First antipsychotic treatment ever, i.e., patient has never been treated with antipsychotics before and antipsychotic treatment given in this study will be the first antipsychotic treatment that the patient will have ever received On clozapine during the last 3 months Patients who remain at imminent risk of suicide even after clinical intervention Serious unstable medical condition, including recent and present clinically relevant laboratory abnormalities

Primary outcomes:
measure: Improved efficacy for non-acute patients transitioned due to lack of efficacy, as measured by the total PANSS score at endpoint versus baseline.
timeFrame: Baseline to 6 months or early discontinuation
measure: Improved efficacy for acute patients, as measured by the total PANSS score at endpoint versus baseline.
timeFrame: Baseline to 6 months or early discontinuation
measure: Maintained efficacy for non-acute patients transitioned for other reasons based on PANSS score at endpoint versus baseline.
timeFrame: Baseline to 6 months or early discontinuation
Secondary outcomes:
measure: Change from baseline in Clinical Global Impression-Severity Scale [CGI-S]
timeFrame: Baseline, week 1, month 1, 2, 3 and 6
measure: Change from baseline in personal and social functioning (Personal and Social Performance Scale [PSP])
timeFrame: Baseline, week 1, month 1, 2, 3 and 6
measure: Change from baseline in Health status (Self-reported health status questionnaire [SF-36])
timeFrame: Baseline, month 3 and 6
measure: Change from baseline in Measure of Health Outcome (EQ-5D)
timeFrame: Baseline, month 3 and 6
measure: Change from baseline in Patient well-being (Subjective Well-Being under Neuroleptics Scale [SWN-S]);
timeFrame: Baseline, month 3 and 6
Other outcomes:
Locations:
city: Salzburg N/A
country: Austria
city: Brussel
country: Belgium
city: Dave
country: Belgium
city: Diest
country: Belgium
city: Kruishoutem
country: Belgium
city: Liege
country: Belgium
city: Melle
country: Belgium
city: Roeselare
country: Belgium
city: Sint-Denijs-Westrem
country: Belgium
city: Tournai
country: Belgium
city: Rijeka
country: Croatia
city: Zagreb
country: Croatia
city: Aalborg
country: Denmark
city: København V
country: Denmark
city: Randers
country: Denmark
city: Tallinn
country: Estonia
city: Bar Le Duc
country: France
city: Bron
country: France
city: Clermont Ferrand
country: France
city: Dax
country: France
city: Dijon Cedex
country: France
city: Dole
country: France
city: Lille
country: France
city: Limoges Cedex 1
country: France
city: Montpellier
country: France
city: Nimes
country: France
city: Paris
country: France
city: Saint Nazaire
country: France
city: St Priest En Jarez
country: France
city: Strasbourg Cedex
country: France
city: Villejuif Cedex
country: France
city: Bad Saarow
country: Germany
city: Berlin
country: Germany
city: Bielefeld
country: Germany
city: Bochum
country: Germany
city: Butzbach
country: Germany
city: Dresden
country: Germany
city: Gelsenkirchen
country: Germany
city: Greifswald
country: Germany
city: Hamburg
country: Germany
city: Heidelberg
country: Germany
city: Königsbrück
country: Germany
city: Mittweida
country: Germany
city: Oranienburg
country: Germany
city: Regensburg
country: Germany
city: Stralsund
country: Germany
city: Ulm
country: Germany
city: Westerstede
country: Germany
city: Würzburg
country: Germany
city: Arta
country: Greece
city: Athens
country: Greece
city: Katerini
country: Greece
city: Thessalonikis
country: Greece
city: Thessaloniki
country: Greece
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Pécs
country: Hungary
city: Pardesia
country: Israel
city: Ramat Gan
country: Israel
city: Tirat Hacarmel
country: Israel
city: Daugavpils
country: Latvia
city: Jelgava
country: Latvia
city: Liepaja
country: Latvia
city: Riga
country: Latvia
city: Sigulda
country: Latvia
city: Strenci
country: Latvia
city: Panevezys
country: Lithuania
city: Vilnius
country: Lithuania
city: Groningen
country: Netherlands
city: Almada N/A
country: Portugal
city: Angra Do Heroísmo
country: Portugal
city: Castelo Viegas N/A
country: Portugal
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Alcorcon
country: Spain
city: Alicante
country: Spain
city: Barcelona
country: Spain
city: Burgos
country: Spain
city: Coslada
country: Spain
city: Elche
country: Spain
city: Madrid
country: Spain
city: Malaga N/A
country: Spain
city: Palma De Mallorca
country: Spain
city: San Juan De Alicante
country: Spain
city: Sant Boi De Llobregat
country: Spain
city: Santa Coloma De Gramenet
country: Spain
city: Vigo
country: Spain
city: Zamora
country: Spain
city: Zaragoza
country: Spain
city: Göteborg
country: Sweden
city: Lidingö
country: Sweden
city: Malmö
country: Sweden
city: Mölndal
country: Sweden
city: Spånga
country: Sweden
city: Upplands-Väsby
country: Sweden
city: Solothurn
country: Switzerland
city: Zürich
country: Switzerland
city: Ankara N/A
country: Turkey
city: Ankara
country: Turkey
city: Diyarbakir
country: Turkey
city: Gaziantep
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Trabzon
country: Turkey
city: Dnepropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Glevakha
country: Ukraine
city: Ivano-Frankivsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kharkov
country: Ukraine
city: Kiev
country: Ukraine
city: Lvov
country: Ukraine
city: Odessa
country: Ukraine
city: Poltava
country: Ukraine
city: Simferopol
country: Ukraine
city: Smela
country: Ukraine
city: Ternopil
country: Ukraine
city: Uzhgorod
country: Ukraine
city: Yevpatoria
country: Ukraine
city: Barnet
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Coventry
country: United Kingdom
city: Darlington
country: United Kingdom
city: Lincoln
country: United Kingdom
city: London
country: United Kingdom
city: Prescott
country: United Kingdom
city: Stoke-On-Trent
country: United Kingdom
Study officials:
affiliation: Janssen-Cilag International NV
name: Janssen-Cilag International NV Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Schreiner A, Bergmans P, Cherubin P, Keim S, Rancans E, Bez Y, Parellada E, Carpiniello B, Vidailhet P, Hargarter L. A prospective flexible-dose study of paliperidone palmitate in nonacute but symptomatic patients with schizophrenia previously unsuccessfully treated with oral antipsychotic agents. Clin Ther. 2014 Oct 1;36(10):1372-88.e1. doi: 10.1016/j.clinthera.2014.08.014. Epub 2014 Oct 23.