Long-Term Efficacy and Safety of Paliperidone 6-Month Formulation: An Open-Label 2-Year Extension of a 1-Year Double-Blind Study in Adult Participants With Schizophrenia

Abstract

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.

Keywords: Long-term efficacy; long-acting injectable; open-label extension; paliperidone palmitate 6-month; schizophrenia.

Figure 1.

Study design of the double-blind study and open-label extension study. ^aThe initial dose of PP6M in OLE study was determined based on the dose level (“moderate” or “higher”) that the participant was receiving during the DB phase. The PP6M dose level was to be adjusted (to 700 or 1000 mg eq.) later in the study (at visits 3, 5, and 7), based on clinical judgment. However, the long-acting nature of PP6M means a dose change could take many months to become apparent. ↑, PP6M injection; DB, double-blind; EOS, End of Study; OLE, open-label extension; PP3M, paliperidone palmitate 3-month formulation; PP6M, paliperidone palmitate 6-month formulation.

Figure 2.

Kaplan Meier estimates of time to relapse during the open-label extension. PP6M, paliperidone palmitate 6-month formulation.

Figure 3.

Mean (±SE) (A) CGI-S, (B) PSP total, (C) PANSS total scores, over time from double-blind study to end of open-label extension. CGI-S, Clinical Global Impression-Severity; DB, double-blind; OL, open-label; PANSS, Positive and Negative Symptom Scale; PSP, Personal and Social Performance; PP3M, paliperidone palmitate 3-month product; PP6M, paliperidone palmitate 6-month product; SE, standard error. Note: Lower scores in PANSS and CGI indicate improvement and higher scores in PSP denote an improvement.