Clinical trial NCT01081769: Prevention of Relapse With Injectable Paliperidone Palmitate Versus Oral Antipsychotics
Official title: A 24-month, Prospective, Randomized, Active-Controlled, Open-Label, Rater-Blinded, Multicenter, International Study of the Prevention of Relapse Comparing Long-Acting Injectable Paliperidone Palmitate to Treatment as Usual With Oral Antipsychotic Monotherapy in Adults With Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Keywords: Schizophrenia
paliperidone palmitate
Invega
Intramuscular injection
Oral antipsychotics
Relapse
Lead sponsor: Janssen-Cilag International NV
Sponsor class: INDUSTRY
First posted: 2010-03-05
Enrollment: 769
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
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 assess the efficacy (how well the drug works; primarily through the time to relapse) of long-acting injectable paliperidone palmitate compared to treatment as usual with orally administered antipsychotics in monotherapy over 24 months in the treatment of recently diagnosed (1-5 years since diagnosis) schizophrenia.

Detailed description: This is a randomized (study drug assigned by chance), open-label (both physician and patient know the name of the assigned drug), rater-blinded (the person who assesses the condition of the patient does not know the name of the assigned drug), active-controlled, parallel-group, multicenter, prospective international study of paliperidone palmitate versus treatment as usual with oral antipsychotic agents in monotherapy in the prevention of relapse (return of symptoms). Patients who have been recently diagnosed with schizophrenia (within 5 years) and are suffering from a schizophrenic relapse (return of symptoms of schizophrenia) will be enrolled. This study consists of a 2-week initial acute oral treatment phase, followed by a treatment phase (core phase) until relapse or up to maximally 24 months, whichever comes first. Prior to a 2-week oral treatment phase, patients will be randomly (by chance) assigned in a 1:1 ratio to receive treatment with paliperidone palmitate injection (once-monthly) or oral antipsychotic medication (daily). Patients randomized to paliperidone palmitate will first receive oral paliperidone ER once daily for 2 weeks followed by paliperidone palmitate injections at a dose of 150 mg eq. on Day 1, 100 mg eq. on Day 8 both in the deltoid muscle and 75 mg eq. on Day 38 and doses in a dose range of 25 to 150 mg eq. in either the deltoid or the gluteal muscle thereafter. Patients randomized to oral comparator arm will receive oral antipsychotics (haloperidol, paliperidone ER, risperidone, olanzapine, quetiapine or aripiprazole) as per investigator discretion and prescribed according to the label. Total treatment duration is maximally 24 months. During the 24 month treatment phase, investigators will be allowed to flexibly decrease or increase the dose of paliperidone palmitate with one dose level in the range of 25 to 150 mg eq. or the oral antipsychotic in the respective locally approved dose range, all according to the patient's clinical needs. The primary endpoint of the 24-month treatment phase will be the time to relapse. Safety will be monitored by evaluating Adverse Events (AEs), rating of extrapyramidal symptoms (symptoms like abnormal muscle movements, abnormal movements of the tongue or jaw, slow or sustained muscle contractions, muscle spasms, shaking, abnormal movements of the eyes, involuntary muscle contractions, slow movements, or restlessness), vital signs measurements (including heart rate and blood pressure), body weight and physical examination findings. A urine pregnancy test will be performed in females of childbearing potential. Adverse events (unintended, but not necessarily unexpected, results of therapy that can be unpleasant or dangerous), associated concomitant medications, and symptoms of relapse will be recorded as needed.

Eligibility criteria: Inclusion Criteria:

* Have been meeting the diagnostic criteria for schizophrenia for 1 to 5 years before screening, and have a history of treatment with antipsychotics
* Have a history of two or more relapses requiring psychiatric hospitalization in the preceding 24 months, which may include the current acute episode
* Experiencing at screening an acute schizophrenic episode with a Positive And Negative Syndrome Scale (PANSS) total score at screening between 70 and 120, inclusive
* Be healthy on the basis of physical examination, medical history and vital signs performed at screening
* Woman must be postmenopausal (for at least 1 year) or surgically sterile or abstinent or be practicing an effective method of birth control, must agree to continue to use the same method of contraception throughout the study and must have a negative urine pregnancy test at screening
* be able to fill out questionnaires
* 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:

* Patients that have never been treated with antipsychotics before
* Treatment resistant patient and/or currently (i.within the last 3 months) treated with clozapine
* Substance dependence within 6 months prior to entry and current intravenous drug use or abuse
* allergies, hypersensitivity, or intolerance to risperidone or paliperidone or excipients
* treatment with a long-acting injectable antipsychotic within three injection cycles prior to screening
* newly started psychotherapy program within the two months preceding the treatment phase baseline
* evidence of clinically significant hepatic, renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances in the past 6 months (as determined by medical history, clinical laboratory or ECG results, or physical examination) that would increase the risk associated with taking study medication or would confound the interpretation of the study
* history or current symptoms of tardive dyskinesia or neuroleptic malignant syndrome
* involuntarily hospitalized patient
* pregnant or breast-feeding females

Primary outcomes:
measure: Time to First Relapse Event
timeFrame: from baseline (Day 1 of core phase) up to maximally 24 months.
measure: Number of Participants With a Relapse Event
timeFrame: from baseline (Day 1 of core phase) up to maximally 24 months
Secondary outcomes:
measure: Percentage of Treatment Responders
timeFrame: from baseline (day 1 of core phase) up to maximally 24 months
measure: Change From Baseline in PANSS Total Score
timeFrame: Baseline, day 8, month 1, 2, 3, 4, 6, 9, 12, 15, 18, 21, 24
measure: Change From Baseline in PANSS Subscale Score
timeFrame: Baseline (day 1 of core phase), day 8, month 12, 24
measure: Change From Baseline in PANSS Marder Factor Scores
timeFrame: Baseline (day 1 of core phase), day 8, month 12 and 24
measure: Change From Baseline in Clinical Global Impression Severity (CGI-S) Score
timeFrame: Baseline (day 1 of core phase), day 8, month 1, 2, 3, 4, 6, 9, 12, 15, 18, 21, 24
measure: Clinical Global Impression-Change (CGI-C)
timeFrame: Month 24 and endpoint
measure: Changes From Baseline in Personal and Social Performance (PSP) Total Score
timeFrame: baseline (day 1 of core phase), month 1, 3, 6, 9, 12, 15, 18, 21 and 24
measure: Change From Baseline in Short Form-36 Health Survey (SF-36)
timeFrame: baseline (day 1 of core phase), month 6, 12 and 24
measure: Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) VAS Score
timeFrame: baseline (day 1 of core phase), month 6, 12 and 24
measure: Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) Index Score
timeFrame: baseline (day 1 of core phase), month 6, 12 and 24
measure: Change From Baseline in Subjective Well-Being Under Neuroleptics-Short Form (SWN-S) Total Score
timeFrame: baseline (day 1 of core phase), month 6, 12 and 24
measure: Change From Baseline in Patient's Treatment Satisfaction
timeFrame: baseline (day 1 of core phase), month 12 and 24
measure: Change From Baseline in Physician's Treatment Satisfaction
timeFrame: baseline (day 1 of core phase), month 12 and 24
Other outcomes:
Locations:
city: Wien
country: Austria
city: Bertrix
country: Belgium
city: Gent
country: Belgium
city: Liège
country: Belgium
city: Oostende
country: Belgium
city: Bourgas
country: Bulgaria
city: Plovdiv N/A
country: Bulgaria
city: Radnevo N/A
country: Bulgaria
city: Zagreb
country: Croatia
city: Brno
country: Czech Republic
city: Litomerice
country: Czech Republic
city: Olomouc 9
country: Czech Republic
city: Praha 10
country: Czech Republic
city: Praha
country: Czech Republic
city: Prerov
country: Czech Republic
city: Alexandria
country: Egypt
city: Cairo
country: Egypt
city: Talinn
country: Estonia
city: Tartu N/A
country: Estonia
city: Colombes Cedex
country: France
city: La Seyne Sur Mer
country: France
city: Limoges N/A
country: France
city: Metz Cedex 01
country: France
city: Paris
country: France
city: Saint Avé
country: France
city: Berlin
country: Germany
city: Bochum
country: Germany
city: Mannheim
country: Germany
city: Munchen
country: Germany
city: München
country: Germany
city: Thessalonikis
country: Greece
city: Budapest
country: Hungary
city: Kalocsa
country: Hungary
city: Nagykallo
country: Hungary
city: Sopron
country: Hungary
city: Bat-Yam
country: Israel
city: Beer Yaakov
country: Israel
city: Hod-Hasharon
country: Israel
city: Ramat-Gan
country: Israel
city: Tirat Hacarmel
country: Israel
city: Amman
country: Jordan
city: Goyang
country: Korea, Republic of
city: Incheon
country: Korea, Republic of
city: Kyounggi
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Siauliai
country: Lithuania
city: Vilnius
country: Lithuania
city: Chelmno
country: Poland
city: Gdansk
country: Poland
city: Torun N/A
country: Poland
city: Zabki
country: Poland
city: Arad
country: Romania
city: Bucharest
country: Romania
city: Jebel
country: Romania
city: Oradea
country: Romania
city: Sibiu
country: Romania
city: Ekaterinburg Na
country: Russian Federation
city: Krasnodar N/A
country: Russian Federation
city: Nizny Novgorod
country: Russian Federation
city: Samara
country: Russian Federation
city: Saratov
country: Russian Federation
city: St Petersburg N/A
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: St-Petersburg
country: Russian Federation
city: Tomsk
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Bratislava
country: Slovakia
city: Michalovce
country: Slovakia
city: Rimavska Sobota
country: Slovakia
city: Cape Town
country: South Africa
city: Pretoria
country: South Africa
city: Barcelona
country: Spain
city: Burgos
country: Spain
city: Elche
country: Spain
city: Madrid
country: Spain
city: Sant Boi De Llobregat
country: Spain
city: Zamora
country: Spain
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Istanbul
country: Turkey
city: Manisa Turkey
country: Turkey
city: Zonguldak
country: Turkey
city: Dnipropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Glevakha
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kharkov
country: Ukraine
city: Kherson
country: Ukraine
city: Kiev
country: Ukraine
city: Lviv
country: Ukraine
city: Odessa
country: Ukraine
city: Poltava
country: Ukraine
city: Simferopol
country: Ukraine
city: Uzhgorod
country: Ukraine
city: Birmingham
country: United Kingdom
city: Exeter
country: United Kingdom
city: London
country: United Kingdom
city: Warrington
country: United Kingdom
Study officials:
affiliation: Janssen-Cilag International NV
name: Janssen-Cilag International NV Clinical Trial
role: STUDY_DIRECTOR
References: