Search

Purpose. This post hoc analysis assessed the importance of proper paliperidone palmitate (PP) dose preparation prior to administration and evaluated injection site reactions after dorsogluteal injection of PP once-every-6-months (PP6M) and once-every-3-months (PP3M) formulations from a double-blind (DB) noninferiority study. Design and Methods. Clinically stable patients receiving moderate/high doses of PP once-monthly (PP1M) (156mg/mL; 234mg/1.5mL) or PP3M (546mg/1.75mL; 819mg/2.63mL) were randomly assigned 2:1 to corresponding dorsogluteal injections of PP6M (1092mg/3.5mL; 1560mg/5mL) or PP3M (546mg/1.75mL; 819mg/2.63mL) during a 12-month DB phase. Patients receiving PP6M injections received alternating matching placebo injections every 3months between active doses to maintain blinding. Prior to administration, each PP formulation was prepared per specific instructions to ensure complete resuspension of the medication. Findings. Of 895 PP6M injections, one of two incomplete injections was possibly related to insufficient shaking before administration; neither resulted in an adverse reaction. After dorsogluteal administration, 59 of 478 patients who received PP6M (12.3%) and 11 of 224 patients who received PP3M (4.9%) reported an injection site-related treatment-emergent adverse event (TEAE), with pain being the most commonly reported (7.7% and 4.0%, respectively). Patient-reported pain decreased from baseline to end point in both groups. During the DB phase, injection site-related TEAEs associated with PP6M injections up to 5mL and PP3M injections up to 2.63mL were mild to moderate in severity; none were reported as serious, resulted in treatment discontinuation, or required dermatological consultation. Practice Implications. These results inform provider and patient expectations of PP6M administration and reinforce the importance of proper PP dose preparation and administration; future work could assess safety data from real-world clinical practice. This trial is registered with NCT03345342., Author(s): Steven Krozer [1]; Karen L. Johnston (corresponding author) [2]; Dean Najarian [2]; Steven Wang [3]; Sherry Fua [2]; Jennifer Kern Sliwa [2]; Oliver Lopena [2] 1. Introduction Long-acting injectable [...]

Background Paliperidone palmitate 6-month (PP6M) demonstrated noninferiority to paliperidone palmitate 3-month in preventing relapse in patients with schizophrenia in a phase 3 double-blind (DB) study (NCT03345342). Here, we report long-term efficacy and safety results from a 2-year single-arm, open-label extension (OLE; NCT04072575) of this DB study. Methods Participants who completed the DB study without relapse were enrolled and followed-up every 3 months up to 2 years. Participants received 4 PP6M gluteal injections (700/1000 mg eq.) at baseline, 6-month, 12-month, and 18-month visits. Efficacy endpoints included assessment of relapse, Positive and Negative Syndrome Scale total score, Personal and Social Performance score, and Clinical Global Impression-Severity scale change from baseline. Safety was assessed by treatment-emergent adverse events (TEAEs), physical examinations, and laboratory tests. Results Of 178 participants enrolled, 154 (86.5%) completed the OLE (mean age: 40.4 years, men: 70.8%; mean duration of PP6M exposure during OLE: 682.1 days). Overall, 7/178 (3.9%) participants relapsed between 20 and 703 days after enrolment. Mean (SD) changes from baseline to endpoint were as follows: Positive and Negative Syndrome Scale total score, 0.7 (8.22); Clinical Global Impression-Severity, 0.0 (0.51); and Personal and Social Performance Scale, 0.5 (7.47). Overall, 111/178 participants (62.4%) reported ≥1 TEAE; most common (>5%) TEAEs were headache (13.5%) and increased blood prolactin/hyperprolactinemia (18.0%); 8/178 (4.5%) participants experienced serious TEAEs, and 6/178 (3.4%) participants withdrew due to TEAEs. No deaths were reported. Conclusions The relapse rate observed with PP6M during the 2-year OLE was low (3.9%). Clinical and functional improvements demonstrated in the DB study were maintained during OLE, and no new safety concerns were identified. Trial registration ClinicalTrials.gov Identifier: NCT04072575; EudraCT number: 2018-004532-30. [ABSTRACT FROM AUTHOR]

Background This double-blind (DB), randomized, parallel-group study was designed to evaluate efficacy and safety of paliperidone palmitate 6-month (PP6M) formulation relative to paliperidone palmitate 3-month (PP3M) formulation in patients with schizophrenia. Methods Following screening, patients entered an open-label (OL) maintenance phase and received 1 injection cycle of paliperidone palmitate 1-month (PP1M; 100 or 150 mg eq.) or PP3M (350 or 525 mg eq.). Clinically stable patients were randomized (2:1) to receive PP6M (700 or 1000 mg eq. gluteal injections) or PP3M (350 or 525 mg eq.) in a 12-month DB phase; 2 doses of PP6M (corresponding to doses of PP1M and PP3M) were chosen. Results Overall, 1036 patients were screened, 838 entered the OL phase, and 702 (mean age: 40.8 years) were randomized (PP6M: 478; PP3M: 224); 618 (88.0%) patients completed the DB phase (PP6M: 416 [87.0%]; PP3M: 202 [90.2%]). Relapse rates were PP6M, 7.5% (n = 36) and PP3M, 4.9% (n = 11). The Kaplan-Meier estimate of the difference (95% CI) between treatment groups (PP6M − PP3M) in the percentages of patients who remained relapse free was −2.9% (−6.8%, 1.1%), thus meeting noninferiority criteria (95% CI lower bound is larger than the pre-specified noninferiority margin of −10%). Secondary efficacy endpoints corroborated the primary analysis. Incidences of treatment-emergent adverse events were similar between PP6M (62.1%) and PP3M (58.5%). No new safety concerns emerged. Conclusions The efficacy of a twice-yearly dosing regimen of PP6M was noninferior to that of PP3M in preventing relapse in patients with schizophrenia adequately treated with PP1M or PP3M. Trial Registration Clinical Trials.gov identifier: NCT03345342 [ABSTRACT FROM AUTHOR]

Background: This double-blind (DB), randomized, parallel-group study was designed to evaluate efficacy and safety of paliperidone palmitate 6-month (PP6M) formulation relative to paliperidone palmitate 3-month (PP3M) formulation in patients with schizophrenia., Methods: Following screening, patients entered an open-label (OL) maintenance phase and received 1 injection cycle of paliperidone palmitate 1-month (PP1M; 100 or 150 mg eq.) or PP3M (350 or 525 mg eq.). Clinically stable patients were randomized (2:1) to receive PP6M (700 or 1000 mg eq., gluteal injections) or PP3M (350 or 525 mg eq.) in a 12-month DB phase; 2 doses of PP6M (corresponding to doses of PP1M and PP3M) were chosen., Results: Overall, 1036 patients were screened, 838 entered the OL phase, and 702 (mean age: 40.8 years) were randomized (PP6M: 478; PP3M: 224); 618 (88.0%) patients completed the DB phase (PP6M: 416 [87.0%]; PP3M: 202 [90.2%]). Relapse rates were PP6M, 7.5% (n = 36) and PP3M, 4.9% (n = 11). The Kaplan-Meier estimate of the difference (95% CI) between treatment groups (PP6M - PP3M) in the percentages of patients who remained relapse free was -2.9% (-6.8%, 1.1%), thus meeting noninferiority criteria (95% CI lower bound is larger than the pre-specified noninferiority margin of -10%). Secondary efficacy endpoints corroborated the primary analysis. Incidences of treatment-emergent adverse events were similar between PP6M (62.1%) and PP3M (58.5%). No new safety concerns emerged., Conclusions: The efficacy of a twice-yearly dosing regimen of PP6M was noninferior to that of PP3M in preventing relapse in patients with schizophrenia adequately treated with PP1M or PP3M., Trial Registration: Clinical Trials.gov identifier: NCT03345342., (© The Author(s) 2021. Published by Oxford University Press on behalf of CINP.)