Adverse Event of INVEGA TRINZA - Upper Respiratory Tract Infection

Summary

• Upper respiratory tract infection (URTI) was among the most common adverse events with an incidence of 10% in the INVEGA TRINZA-treated patients vs an incidence of 4% for placebo patients during the double-blind phase of the long-term relapse prevention trial.^1,2
• URTI, as described in the INVEGA TRINZA Prescribing Information, represents a combination of terms that includes URTI, nasopharyngitis, pharyngitis and rhinitis.² Nasopharyngitis contributed to the largest percentage of adverse events for this combination term (5.6% during the double-blind phase of the relapse prevention study).³
• Based on the pivotal relapse prevention trial for INVEGA TRINZA, the incidence of URTI-related terms was rated as mild to moderate and no patients discontinued based on a report of URTI.³
  • In all cases in the double-blind phase of the trial, investigators reported that URTI adverse events were not related to study drug.³
• In a randomized, multicenter, double-blind study assessing the noninferiority of INVEGA TRINZA to INVEGA SUSTENNA, nasopharyngitis was reported in 7% of patients in the INVEGA TRINZA group and in 6% of patients in the INVEGA SUSTENNA group.⁴
• In a randomized, multicenter, double-blind study assessing the noninferiority of INVEGA TRINZA and INVEGA HAFYERA, URTI and nasopharyngitis, respectively, were reported in 9 (4.0%) and 13 (5.8%) patients in the INVEGA TRINZA group and 24 (5.0%) and 22 (4.6%) patients in the INVEGA HAFYERA group during the doubleblind phase.⁵
  • In a post hoc subgroup analysis of patients enrolled in European investigational sites, nasopharyngitis and rhinitis, respectively, were reported in 10 (8.1%) and 4 (3.2%) patients in the INVEGA TRINZA group and 16 (6.2%) and 5 (1.9%) patients in the INVEGA HAFYERA group during the double-blind phase.⁶
• In DREaM (Disease Recovery Evaluation and Modification), a 20-month, prospective, delayed-start, matched-control, double-randomized, open-label, flexible-dose, multicenter study, time to first treatment failure (TtFTF) of INVEGA SUSTENNA or INVEGA TRINZA (PP) vs oral antipsychotics (OAPs) in patients with recent-onset schizophrenia or schizophreniform disorder was evaluated. During part II of the study, 6.4% and 2.5% of patients in the PP and OAPs groups, respectively, experienced nasopharyngitis. During part III, 6.1% of patients in the PP/PP group, no patients in the OAP/PP group, and 6.3% of patients in the OAP/OAP group reported nasopharyngitis. During the extended disease progression (EDP) phase, 10.2% and 9.5% of patients in the PP/PP and OAP/OAP groups, respectively, experienced nasopharyngitis.⁷
• In CASPAR (Clinical Study to Assess the Treatment of Schizophrenia with Paliperidone Palmitate in Rwandan Healthcare Settings), a 66-week, multicenter, open-label study evaluating treatment with INVEGA SUSTENNA followed by INVEGA TRINZA in young adults (aged 18-35) with schizophrenia, nasopharyngitis was reported in 13 (14.1%) patients during the overall follow-up period. Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity, and no new safety concerns were identified.⁸

PRODUCT LABELING

Please refer to the following section of the Full Prescribing Information that is relevant to your inquiry: ADVERSE REACTIONS.²

CLINICAL DATA

Pivotal Relapse Prevention Trial

URTI is reported in the United States (US) Prescribing Information as a combination of terms that includes URTI, nasopharyngitis, pharyngitis and rhinitis.  During the open-label phase of the pivotal relapse prevention trial, 5% of patients  experienced URTI.² The reporting rate for individual terms during the 29–week, open-label phase of the trial is described in Table: Upper Respiratory Tract Adverse Events During the Open-Label Phase of the Pivotal Relapse Prevention Study.

During the double-blind phase of the relapse prevention study, nasopharyngitis represented the largest proportion of the URTI-combined terms (n=9; 5.6%).^1,3  The reporting rate for the individual URTI adverse event terms during the double-blind phase of the trial is described in Table: Upper Respiratory Tract Adverse Events During the Double-Blind Phase of the Pivotal Relapse Prevention Study.

There were 16 URTI events reported in the INVEGA TRINZA group during the double-blind phase of the study; 13 events were reported to be mild, and 3 were reported as moderate. None of the events led to study discontinuation. In all cases in the double-blind phase of the trial, investigators reported that URTI adverse events were not related to study drug.³

Noninferiority Trial

In a randomized, double-blind, parallel-group, multicenter, noninferiority study of INVEGA TRINZA and INVEGA SUSTENNA, patients completed an open-label treatment phase with INVEGA SUSTENNA before being randomized to INVEGA TRINZA (n=504) or to INVEGA SUSTENNA (n=512). In the double-blind phase, nasopharyngitis was reported in 7% of the INVEGA TRINZA group and 6% of the INVEGA SUSTENNA group.⁴

In a randomized, double-blind, parallel-group, multicenter, open-label, noninferiority study of INVEGA TRINZA and INVEGA HAFYERA, patients completed an open-label treatment with INVEGA SUSTENNA or INVEGA TRINZA before being randomized to INVEGA TRINZA (n=224) or INVEGA HAFYERA (n=478) in a 12-month double-blind phase. In the open-label phase, URTI and nasopharyngitis were reported in 19 (2.3%) and 22 (2.6%) patients, respectively, in the INVEGA SUSTENNA/INVEGA TRINZA group. In the double-blind phase, URTI and nasopharyngitis, respectively, were reported in 9 (4.0%) and 13 (5.8%) patients in the INVEGA TRINZA group and 24 (5.0%) and 22 (4.6%) patients in the INVEGA HAFYERA group.⁵ A post hoc subgroup analysis of this noninferiority study evaluated 384 patients with schizophrenia who were enrolled in European investigational sites and received INVEGA TRINZA (n=124) or INVEGA HAFYERA (n=260). In the doubleblind phase, nasopharyngitis and rhinitis, respectively, were reported in 10 (8.1%) and 4 (3.2%) patients in the INVEGA TRINZA group and 16 (6.2%) and 5 (1.9%) patients in the INVEGA HAFYERA group.

DREaM Study

DREaM was a 20-month, prospective, delayed-start, matched-control, double-randomized, open-label, flexible-dose, multicenter study that evaluated TtFTF of PP vs OAPs and changes in cognition, functioning, and intracortical myelin volume in patients with recent-onset schizophrenia or schizophreniform disorder. The study consisted of the following phases⁷:

• Part I (2 months): All randomized patients received oral paliperidone or risperidone for 2 months to establish tolerability.
• Part II (9 months): Patients who demonstrated adequate tolerability were randomized in a 1:2 ratio to receive either PP or OAP.
• Part III (9 months): Patients completing OAP treatment in part II were matched and rerandomized to either continue treatment with OAP (OAP/OAP) or switch to PP (OAP/PP) in a 1:1 ratio. Patients on PP remained on PP (PP/PP).
• An EDP phase spanning from part II through part III (18 months) compared differences between PP/PP and OAP/OAP groups and therefore only evaluated patients on the same treatment regimen for all 18 months.

In parts II and III, PP treatment was defined as INVEGA SUSTENNA for a minimum of 4 months (5 injections), followed by INVEGA TRINZA treatment.⁷

During part II of the study, nasopharyngitis was experienced by 6.4% of patients in the PP group and 2.5% of patients in the OAP group. During part III, 6.1% of patients in the PP/PP group, no patients in the OAP/PP group, and 6.3% of patients in the OAP/OAP group reported nasopharyngitis. During the EDP phase, 10.2% and 9.5% of patients in the PP/PP and OAP/OAP groups, respectively, experienced nasopharyngitis.⁷

CASPAR Study

CASPAR was a 66-week, multicenter, single-arm, open-label interventional study that evaluated the efficacy and safety of INVEGA TRINZA in young adults (aged 18-35) with schizophrenia. Patients initially received oral antipsychotics during an observation/run-in phase and were subsequently transitioned to INVEGA SUSTENNA for at least 17 weeks, followed by 24 weeks of maintenance treatment with INVEGA TRINZA. Of the 93 patients enrolled, 86 (92.5%) completed the study (92 were in lead-in and maintenance phase received INVEGA SUSTENNA and 89 in maintenance phase received INVEGA TRINZA). During the overall follow-up period, at least 1 TEAE was reported in 69 (75.0%) patients. Nasopharyngitis was among the most frequently observed TEAEs, reported in 8 (8.6%) patients during the observational/run-in phase and 6 (6.5%) patients during the lead-in/maintenance phase, with an overall incidence of 13 (14.1%) during the follow-up period. Most TEAEs were mild to moderate in severity, and no new safety concerns were identified.⁸

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 24 July 2026.