Invega® Significantly Reduced Symptoms Of Schizophrenia In Acutely Ill, Hospitalised Patients Compared To Quetiapine

Main Category: Schizophrenia
Article Date: 16 Oct 2007 - 8:00 PDT

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Yesterday, Janssen-Cilag presented for the first time in Europe, new preliminary data that show acutely ill, hospitalised patients with schizophrenia experienced significant improvement in symptoms after taking INVEGA® (paliperidone prolonged-release tablets) as compared to Seroquel® (quetiapine) or placebo. Symptom improvement was observed with INVEGA five days into therapy and continued through to the end of the two-week study period,[i].

The primary endpoint was the change in the total Positive and Negative Syndrome Scale (PANSS)[1] at day 14 (monotherapy endpoint for INVEGA vs. quetiapine). The results showed that INVEGA achieved a significant reduction of symptoms of acutely ill, hospitalised patients, compared to quetiapine or placebo after two weeks of treatment measured by the PANSS (p<0.05 and p< 0.001, respectively). INVEGA is the first prolonged-release oral atypical antipsychotic medication and is taken once daily. It was first approved in the United Kingdom on 29 June, 2007 for treatment of schizophrenia.

"Treating patients with an acute exacerbation of schizophrenia is challenging. It is important to explore medications that not only have the potential to achieve effective, acute symptom control but also offer a favourable long-term profile," said Brian Mangan MD, MRC Psych (Consultant Psychiatrist, Craigavon Hospital, Northern Ireland). "These new data show beneficial effects of INVEGA compared to quetiapine in severely ill, hospitalised patients and complement several longer-term studies suggesting this treatment is an effective and tolerable maintenance therapy. This is encouraging for psychiatrists as it offers a viable treatment to add to the therapeutic options available."

In this comparative study, 397 patients with an acute exacerbation of symptoms of schizophrenia were randomised to receive INVEGA, quetiapine or placebo. These patients were either hospitalised or in need of hospitalisation at the start of the trial and willing to remain hospitalised for a minimum of 10 days. The study involved two phases: a two-week monotherapy phase (primary endpoint) followed by a four-week additive therapy phase (secondary endpoint). During the four-week phase, the patients could be prescribed additional psychotropic therapy as clinically indicated to manage psychiatric symptoms.

Recent trials in hospitalised patients have suggested the need for higher doses in the treatment of acute patients.[ii] This study examined the effects of recommended labeled doses while taking into account common clinical practice for this patient population. INVEGA was initiated at the recommended starting dose of 6 mg/day (days one to three) increasing to 9 mg/day on day four. There was an option to increase the dose to 12 mg/day on day eight. Quetiapine was titrated to 600 mg/day by day five with an option to increase the dose to 800 mg/day on day eight. Because this study enrolled severely ill patients with recent onset of symptoms, patients were more likely to require doses near the upper end of the recommended ranges to control their symptoms. The average doses during the monotherapy phase were 10.4 mg/day for INVEGA and 690.9 mg/day for quetiapine.

The primary efficacy endpoint was total change in PANSS score from baseline to the end of the monotherapy phase (day 14). The average PANSS score at baseline was 102.8 (±13.1) for the INVEGA group, 101.6 (± 13.5) for the quetiapine group and 103.8 (± 15.7) for the placebo group. At the end of the monotherapy phase (day 14), the change in the total score from baseline was -23.4 (+1.8) for INVEGA, -17.1(+1.8) for quetiapine and -15.0 (+2.2) for placebo, with INVEGA showing a significant reduction in symptoms over quetiapine (p<0.001) or placebo (p<0.001).

"In acutely ill patients it is important to see an early improvement in symptoms. The results from this study are promising because the symptom reduction with Invega was greater than quetiapine and that this reduction was observed as early as day five," commented Brian Mangan, MD, MRC Psych.

In a separate analysis INVEGA also produced a statistically significant improvement in the reduction in the individual symptom domains of the PANSS scale, which includes positive, negative, disorganised thoughts and uncontrolled hostility/excitement, than quetiapine (p≤0.008) or placebo (p≤0.003) at two weeks. In the additive therapy phase (days 15-42), 52.9 percent of patients taking INVEGA received optional additive therapy compared with 55.4 percent of patients taking quetiapine and 66.7% of patients taking placebo. At the 6-week endpoint significantly greater improvements were seen in the INVEGA group compared with the quetiapine group (p=0.023).

During this study, discontinuation rates due to adverse effects were: INVEGA (4%), quetiapine (10%) and placebo (6%). In the monotherapy phase, adverse events that occurred with an incidence of >10 percent were headache (INVEGA 12%, quetiapine 8% and placebo 14%), somnolence (9%, 12%, 1%), tremor (14%, 5%, 8%), and insomnia (10%, 9%, 11%). In the entire study, adverse events that occurred with an incidence of >10% were headache (INVEGA 15%, quetiapine 12% and placebo 16%), hypertonia (12%, 4%, 4%), sedation (4%, 11%, 4%), somnolence (11%, 15%, 3%), tremor (20%, 8%, 15%), dizziness (4%, 15%, 1%), schizophrenia (6%, 9%, 13%) and insomnia (12%, 10%, 15%).

Notes:

INVEGA (paliperidone prolonged-release tablets) is indicated for the treatment of schizophrenia.

INVEGA was developed by Johnson & Johnson Pharmaceutical Research and Development (J&JPRD). INVEGA prolonged release tablets have been authorised by the Food and Drug Administration since December 2006 and is marketed by Janssen, L.P. in the United States. Upon authorisation by the European Commission, INVEGA prolonged release tablets will be marketed in Europe by the Janssen-Cilag companies.

Janssen-Cilag Ltd (http://www.janssen-cilag.co.uk), manufacturer of Risperdal® Consta™, Risperdal® (risperidone) and Risperdal® Quicklet™ is part of the Johnson & Johnson family of companies, a leading research-based pharmaceutical company, with more than 110,000 employees worldwide and establishments in approximately 50 countries.

References

[1] Positive and Negative Syndrome Scale for Schizophrenia (PANSS) is a standard rating scale used in trials to assess the severity of symptoms. The scale consists of 30 items, which are assessed from absent to extreme, and these are divided into both positive and negative symptoms.

[i] Canuso C, Dirks B, Carothers J et al., A comparative analysis of paliperidone ER and quetiapine in patients with a recent, acute exacerbation of schizophrenia, presented at the 20th Annual U.S. Psychiatric and Mental Health Congress in Orlando, Florida.

[ii] Citrome L, Jaffe A, Levine J, et al., Dosing of quetiapine in schizophrenia: how clinical practice differs from registration studies. J. Clinical Psychiatry 2005 Dec; 66(12): 1512-1516

For further information please go to:
Janssen-Cilag Ltd

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