Clinical Data Demonstrating Time to Relapse With INVEGA TRINZA®

A Long-term Maintenance Trial Demonstrated the Efficacy and Safety of INVEGA TRINZA® vs Placebo1,2

Abbreviated Study Design1,2

study-design

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 trial.1,2

Study Design

A randomized, double-blind, placebo-controlled, long-term maintenance study compared 3-month paliperidone palmitate (INVEGA TRINZA®) with placebo in adults with schizophrenia. Patients were treated for 17 weeks with 1-month paliperidone palmitate (INVEGA SUSTENNA®) during an open-label, flexible-dose stabilization phase, and then a single dose of INVEGA TRINZA® during an open-label maintenance phase. This was followed by a fixed dose of INVEGA TRINZA® or placebo once every 3 months in a variable-duration, double-blind phase.1,2

Inclusion and Exclusion Criteria

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)

*Based on Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV-TR ®)

PANSS=Positive and Negative Syndrome Scale

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

In a Long-term Maintenance Trial, 93% of Adult Patients Treated With INVEGA TRINZA® Remained Relapse-free1

Primary Endpoint: Longer Time to Relapse vs Placebo1,2

Interim Analysis

primary-endpoint

Key Study Observations1,2

  • 7% of patients taking INVEGA TRINZA® relapsed vs 23% of patients taking placebo (P<0.001)1,2
  • Median time to relapse for placebo was 274 days in the double-blind phase1,2
  • Median time to relapse in the INVEGA TRINZA® arm could not be estimated due to low percentage (7.4%) of patients with relapse1,2
  • Due to the significant efficacy of INVEGA TRINZA®, the study was terminated early at the preplanned interim analysis by an Independent Data Monitoring Committee1,2

The study protocol designated that an Independent Data Monitoring Committee perform an interim analysis after 42 relapse events had occurred across both arms of the trial. At that point, the committee decided to terminate the study because of the significant difference in efficacy favoring INVEGA TRINZA®, and the interim analysis became the primary efficacy analysis.1,2

Demonstrated Longer Time to Relapse vs Placebo1,2

Final Analysis

final-analysis

Key Study Observations2

  • 9% of patients taking INVEGA TRINZA® relapsed vs 29% of patients taking placebo (P<0.001)2
  • Median time to relapse for placebo was 395 days in the double-blind phase2
  • Median time to relapse in the INVEGA TRINZA® arm could not be estimated due to low percentage of patients with relapse1,2

Between the interim analysis and the final study closeout, 22 additional patients were randomized, and 14 relapse events occurred across both arms of the trial. Final analysis results—which included these additional patients and relapse events—were consistent with, and confirmed the results of, the interim analysis.2

The safety data in the INVEGA TRINZA® label are based on the final analysis.

Relapse Criteria1,2

Relapse was defined as emergence of ≥1 of the following:

  • Psychiatric hospitalization
  • Increase in PANSS total score*
  • Increase in distinct PANSS item scores
  • Deliberate self-injury or violent behavior
  • Suicidal or homicidal ideation

*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.

PANSS=Positive and Negative Syndrome Scale

Indicated for the treatment of schizophrenia in adults.

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-IV® or current version) where applicable.

Study Phases

Stabilization Phase

A 17-week flexible-dose open-label transition period with 1-month paliperidone palmitate1,2 (first part of a 29-week open-label stabilization phase)

17 weeks N=506
  • Patients had to be clinically stable at the end of this period before receiving INVEGA TRINZA® at the week 17 visit
  • Clinical stability was defined as achieving a PANSS total score <70 at week 17

PANSS=Positive and Negative Syndrome Scale.

Maintenance Phase

A 12-week open-label maintenance period with a single dose of INVEGA TRINZA®1,2 (second part of a 29-week open-label stabilization phase)

12 Weeks n=379
  • Patients received a single dose of INVEGA TRINZA®, which was a 3.5 multiple of the last dose of 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

PANSS=Positive and Negative Syndrome Scale.

Double-Blind Phase

A variable-length double-blind treatment period with INVEGA TRINZA®1,2

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

Early Termination Information

Independently Monitored Study1,2

  • 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

Significant Efficacy Resulted in Early Termination1,2

  • 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 patients treated with INVEGA TRINZA® compared with placebo, and the study was stopped early by an IDMC because efficacy was demonstrated

References: 1. INVEGA TRINZA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; January 2019. 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 November 8, 2019.