Clinical Study

A long-term maintenance trial demonstrated the efficacy and safety of INVEGA TRINZA® in schizophrenia1,2

 

A randomized, double-blind, placebo-controlled, long-term maintenance study compared INVEGA TRINZA® (paliperidone palmitate) (n=160) with placebo (n=145) in adult patients with schizophrenia1,2

Key inclusion criteria1,2:

  • Adult patients (aged 18 to 70 years) with a diagnosis of schizophrenia* for ≥1 year before screening
  • PANSS total score <120 at screening and baseline
  • Patients with acute symptoms (if previously treated with oral antipsychotics) or who were clinically stable (if treated with long-acting injectable antipsychotics)

Key exclusion criteria2:

  • Primary, active DSM-IV® diagnosis other than schizophrenia
  • Significant risk of suicidal behavior
  • History of substance dependence within 6 months before screening
  • Involuntary status in a psychiatric hospital at screening
  • History of neuroleptic malignant syndrome, tardive dyskinesia, or any malignancy in the previous 5 years, except basal cell carcinoma
Approved for the treatment of schizophrenia

The full constellation of symptoms and the relevant diagnostic criteria should be consulted and are available in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5®, or current version), where applicable.1,2

*

Based on Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV-TR®) criteria.
PANSS=Positive and Negative Syndrome Scale.

 
  1. A 17-week flexible-dose open-label transition period (n=506) with the 1-month paliperidone palmitate (first part of a 29-week open-label stabilization phase). Patients had to be clinically stable at the end of this period before receiving INVEGA TRINZA® (paliperidone palmitate) at the Week 17 visit. Clinical stability was defined as achieving a PANSS total score <70 at Week 17.1,2
  2. A 12-week open-label maintenance period (n=379) with a single dose of INVEGA TRINZA® (second part of a 29-week open-label stabilization phase). Patients received a single dose of INVEGA TRINZA®, which was a 3.5 multiple of the last dose of the 1-month paliperidone palmitate. Subjects had to remain clinically stable before entry into the next period (double-blind). Clinical stability was defined as achieving a PANSS total score <70 and scores of ≤4 for 7 specific PANSS items.1,2
  3. A variable-length double-blind treatment period with INVEGA TRINZA® (INVEGA TRINZA®, n=160; placebo, n=145). 305 stabilized patients were randomized 1:1 to continue treatment with INVEGA TRINZA® or placebo until relapse, early withdrawal, or the end of the study. Patients were randomized to the same INVEGA TRINZA® dose received during the open-label phase (ie, 273 mg, 410 mg, 546 mg, or 819 mg) or to placebo, once every 3 months. The mean duration of exposure during the double-blind phase was 175 days in the INVEGA TRINZA® group and 150 days in the placebo group.1,2

The protocol planned for an interim analysis after 42 relapse events and full analysis after 70 relapse events. The interim analysis showed a significantly longer time to relapse in subjects treated with INVEGA TRINZA® (paliperidone palmitate) compared with placebo, and the study was stopped early by an Independent Data Monitoring Committee because efficacy was demonstrated.1,2

An Independent Data Monitoring Committee (IDMC) performed ongoing safety monitoring, an efficacy interim analysis, and provided recommendations about modifying, stopping, or continuing the study. The IDMC consisted of 4 academic psychiatrists and 1 statistician who independently reviewed safety data on a quarterly basis, along with 1 planned unblinded efficacy analysis.1,2

Relapse was defined as emergence of ≥1 of the following1,2:

  • Psychiatric hospitalization
  • ≥25% increase in PANSS total score*
  • Increase in distinct PANSS item scores
  • Deliberate self-injury or violent behavior
  • Suicidal or homicidal ideation
Approved for the treatment of schizophrenia

The full constellation of symptoms and the relevant diagnostic criteria should be consulted and are available in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5®, or current version), where applicable.1,2

*

Defined as a ≥25% increase for 2 consecutive assessments between 3 and 7 days apart for patients scoring >40 at randomization or a 10-point increase for patients scoring ≤40 at randomization.1,2
PANSS=Positive and Negative Syndrome Scale.

 

Secondary efficacy endpoints included changes from double-blind baseline to endpoints in PANSS total score, subscale scores, 5-factor scores, and Clinical Global Impression-Severity (CGI-S) scores.2

PANSS=Positive and Negative Syndrome Scale.

Following stabilization with INVEGA SUSTENNA® (paliperidone palmitate), all patients received 1 dose of INVEGA TRINZA® 12 weeks before randomization in the double-blind phase of the clinical trial1

Abbreviated Study Design

Key study observations1,2:

  • Median time to relapse in the placebo arm of the double-blind phase was 274 days
  • Median time to relapse in the INVEGA TRINZA® arm could not be estimated due to the low percentage (7.4%) of subjects with relapse

References: 1. INVEGA TRINZA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; March 2016. 2. Berwaerts J, Liu Y, Gopal S, et al. Efficacy and safety of the 3-month formulation of paliperidone palmitate vs placebo for relapse prevention of schizophrenia: a randomized clinical trial. JAMA Psychiatry. 2015;72(8):830-839. Supplemental data available at: http://archpsyc.jamanetwork.com/article.aspx?articleid=2211343#tab12. Accessed March 28, 2016.