INVEGA Significantly Reduced Symptoms Of Schizophrenia In Hospitalized Patients
Acutely ill, hospitalized patients with schizophrenia showed significant improvement in symptoms after taking INVEGA (paliperidone) Extended-Release Tablets as compared to SEROQUEL (quetiapine) and placebo. Symptom improvement was observed with INVEGA as early as five days into therapy and continued through the end of the two-week study period.
The primary endpoint was the change in the total Positive and Negative Syndrome Scale (PANSS) score over the first two weeks of the study. The results showed that INVEGA achieved a significant reduction of symptoms of acutely ill, hospitalized patients, compared to SEROQUEL and placebo after two weeks of treatment (p < less than > 0.001).
"In the treatment of patients with an acute exacerbation of schizophrenia, it is important to explore medications that have the potential to achieve effective, acute symptom control. Schizophrenia patients may take two to four weeks to respond fully to treatment, so the fact that noticeable clinical improvement was observed as early as day 5 in these acutely ill patients is very important," said Miranda Chakos, M.D. Professor of Psychiatry, State University of New York at Downstate, Brooklyn, N.Y., and one of the investigators of the trial. "INVEGA is an important treatment option for patients diagnosed with schizophrenia. This trial showed beneficial effects of INVEGA in severely ill, hospitalized patients with an acute exacerbation of schizophrenia."
In the study, 399 patients with an acute exacerbation of symptoms of schizophrenia were randomized to receive INVEGA, SEROQUEL or placebo. These patients were either hospitalized or in need of hospitalization at the start of the trial and willing to remain hospitalized 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, patients could be prescribed additional psychotropic therapy as clinically indicated to manage psychiatric symptoms.
Recent trials in hospitalized patients have suggested the need for higher doses in the treatment of acute patients(2). 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 6mg/day (days one to three) increasing to 9 mg/day on day four. As these patients were acutely ill, there was an option to increase the dose to 12 mg/day on day eight. SEROQUEL 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 SEROQUEL.
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 (plus or minus 13.1) for the INVEGA group, 101.6 (plus or minus 13.5) for the SEROQUEL group, and 103.8 (plus or minus 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 SEROQUEL and -15.0 (2.2) for placebo, with INVEGA showing a significant reduction in symptoms over both SEROQUEL (p < less than > 0.001) and placebo (p < less than > 0.001).
In a separate analysis, INVEGA(TM) also produced a statistically significant improvement in the reduction in the individual symptom domains of the PANSS, which includes positive symptoms, negative symptoms, disorganized thoughts and uncontrolled hostility/excitement, than quetiapine (p < less than or equal to > 0.008) and placebo (p < less than or equal to > 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 SEROQUEL.
Discontinuation rates due to adverse events were: INVEGA (4%), SEROQUEL (10%) and placebo (6%). In the monotherapy phase, adverse events that occurred with an incidence of < greater than > 10 percent were headache (INVEGA 12%, SEROQUEL 8% and placebo 14%), somnolence (9%, 12%, 1%), tremor (14%, 5%, 8%), and insomnia (10%, 9%, 11%). In the additive therapy phase, adverse events that occurred with an incidence of < greater than > 10% were headache (INVEGA 14%, SEROQUEL 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%).
During the study, 8 percent of the INVEGA patients reported a serious adverse event (SAE), compared to 4 percent of SEROQUEL patients and 3 percent of patients on placebo. The only SAE reported in more than two percent of patients was schizophrenia (INVEGA 4%, SEROQUEL 2%, and placebo 0%).
Ortho-McNeil Janssen Scientific Affairs, LLC and Johnson & Johnson Pharmaceutical Research & Development, LLC sponsored this clinical study. Additional details about the study are available upon request.
INVEGA, an atypical antipsychotic medication, was first approved in the U.S. in December 2006. It is approved for the acute and maintenance treatment of schizophrenia in the U.S. and for the treatment of schizophrenia in the E.U.
Worldwide, it is estimated that one person in every 100 develops schizophrenia, one of the most serious types of mental illness. In the United States, there are currently 2 million people with schizophrenia, with men and women affected equally. The disease is marked by positive symptoms (hallucinations and delusions) and negative symptoms (depression, blunted emotions, and social withdrawal), as well as by disorganized thinking.