Improvement of Negative Symptoms in Schizophrenia with Paliperidone Palmitate 1-Month and 3-Month Long-Acting Injectables: Results from a Phase 3 Non-Inferiority Study

Abstract

Background: Negative symptoms in schizophrenia are associated with impairments in social and cognitive functioning leading to substantial long-term disability. Available antipsychotic treatments have demonstrated only modest benefit in the improvement of negative symptoms.

Objective: To compare improvements in negative symptoms among patients treated with paliperidone palmitate 3-month (PP3M) or paliperidone palmitate 1-month (PP1M) long-acting injectable (LAI) formulations.

Methods: Data from a randomized double-blind (DB), phase-3, non-inferiority study in patients with schizophrenia were analyzed. Following screening, patients entered a 17-week open-label (OL) phase to receive flexibly dosed PP1M followed by a 48-week DB phase where patients were randomized (1:1) to receive either PP1M or PP3M. Positive and Negative Syndrome Scale (PANSS) total scores with emphasis on 7-item negative subscale scores for PP1M vs PP3M were assessed.

Results: Of 1429 patients enrolled, 1016 were randomized to receive PP3M (n=504) or PP1M (n=512). At baseline, mean (SD) PANSS negative subscale was 23.2 (4.60) and negative symptom factor score was 22.3 (4.87), indicating moderate-to-severe negative symptoms. Negative subscale and symptoms factor scores showed continuous improvements throughout OL (15.9 [4.99]) and DB (14.9 [4.81]) phases. Mean (SD) changes from DB baseline in the PANSS negative subscale score were comparable between PP1M (-1.4 [3.67]) and PP3M (-1.4 [3.63]) treatment groups.

Conclusion: Treatment with PP3M or PP1M demonstrated comparable improvement in negative symptoms in patients with moderate-to-severe negative symptoms and in patients with prominent negative symptoms. Long-term treatment with PP3M demonstrated benefit, suggesting that continuous antipsychotic medication treatment for >1 year is needed to achieve greater benefit for negative symptoms.

Trial registration: ClinicalTrials.gov Identifier: NCT01515423.

Keywords: negative symptoms; paliperidone palmitate 1-month formulation; paliperidone palmitate 3-month formulation.

Conflict of interest statement

SG, MM, AS and JG are employees of Janssen Research and Development, USA, EK is an employee of Janssen Scientific affairs, USA and KP is an employee of Janssen-Cilag, Germany; all authors hold company stocks. The authors report no other conflicts of interest in this work.

© 2020 Gopal et al.

Figures

Figure 1

Study profile. Abbreviations: PP1M, paliperidone palmitate 1-month formulation; PP3M, paliperidone palmitate 3-month formulation.

Figure 2

Negative symptom factor vs subscale scores over time (ITT analysis set). Abbreviations: DB, Double blind; ITT, intent-to-treat, OL, Open-label.

Figure 3

(A) Total PANSS vs negative subscale scores over time (mITT-DB analysis set). (B) Total PANSS vs negative symptom factor over time (mITT-DB analysis set). Abbreviations: PANSS, Positive and Negative Syndrome Scale for schizophrenia; mITT-DB, modified intent-to-treat double-blind analysis set; SD, standard deviation.

Figure 4

PP1M vs PP3M negative subscale scores change from baseline (DB) over time (mITT-DB analysis set). Abbreviations: PP1M, paliperidone palmitate 1-month formulation; PP3M, paliperidone palmitate 3-month formulation; mITT-DB, modified intent-to-treat double-blind analysis set; SD, standard deviation.

Figure 5

PANSS negative symptom factor score over time in patients with severe negative symptoms factor (≥ 25) at baseline (mITT-DB analysis set). Abbreviations: DB, Double blind; OL, Open-label; PANSS, Positive and Negative Syndrome Scale for Schizophrenia; mITT-DB, modified intent-to-treat double-blind analysis set; SD, Standard deviation.