Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial
<p>Abstract</p> <p>Background</p> <p>This post hoc analysis (trial registration: ClinicalTrials.gov NCT00590577) assessed onset of efficacy and tolerability of acute treatment with once-monthly paliperidone palmitate (PP), a long-acting atypical antipsychotic initiated...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-04-01
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| Series: | Annals of General Psychiatry |
| Online Access: | http://www.annals-general-psychiatry.com/content/10/1/12 |
| _version_ | 1828490986424107008 |
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| author | Ma Yi-Wen Sliwa Jennifer K Bossie Cynthia A Alphs Larry Turner Norris |
| author_facet | Ma Yi-Wen Sliwa Jennifer K Bossie Cynthia A Alphs Larry Turner Norris |
| author_sort | Ma Yi-Wen |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>This post hoc analysis (trial registration: ClinicalTrials.gov NCT00590577) assessed onset of efficacy and tolerability of acute treatment with once-monthly paliperidone palmitate (PP), a long-acting atypical antipsychotic initiated by day 1 and day 8 injections, in a markedly to severely ill schizophrenia population.</p> <p>Methods</p> <p>Subjects entering the 13-week, double-blind trial were randomized to PP (39, 156, or 234 mg [25, 100, and 150 mg eq of paliperidone, respectively]) or placebo. This subgroup analysis included those with a baseline Clinical Global Impressions-Severity (CGI-S) score indicating marked to severe illness. PP subjects received a 234-mg day 1 injection (deltoid), followed by their assigned dose on day 8 and monthly thereafter (deltoid or gluteal). Thus, data for PP groups were pooled for days 4 and 8. Measures included Positive and Negative Syndrome Scale (PANSS), CGI-S, Personal and Social Performance (PSP), and adverse events (AEs). Analysis of covariance (ANCOVA) and last-observation-carried-forward (LOCF) methodologies, without multiplicity adjustments, were used to assess changes in continuous measures. Onset of efficacy was defined as the first time point a treatment group showed significant PANSS improvement (assessed days 4, 8, 22, 36, 64, and 92) versus placebo, which was maintained through end point.</p> <p>Results</p> <p>A total of 312 subjects met inclusion criterion for this subgroup analysis. After the day 1 injection, mean PANSS total scores improved significantly with PP (all received 234 mg) versus placebo at day 4 (<it>P </it>= 0.012) and day 8 (<it>P </it>= 0.007). After the day 8 injection, a significant PANSS improvement persisted at all subsequent time points in the 234-mg group versus placebo (<it>P </it>< 0.05). PANSS improvements were greater from day 36 through end point in the 156-mg group (<it>P </it>< 0.05) and only at end point in the 39-mg group (<it>P </it>< 0.05). CGI-S and PSP scores improved significantly in the 234-mg and 156-mg PP groups versus placebo at end point (<it>P </it>< 0.05 for both, respectively); improvement in the 39-mg group was not significant. The most common AEs for PP-treated subjects (≥10%, any treatment group) were headache, insomnia, schizophrenia exacerbation, injection site pain, and agitation.</p> <p>Conclusions</p> <p>In this markedly to severely ill population, acute treatment with 234 mg PP improved psychotic symptoms compared with placebo by day 4. After subsequent injections, observed improvements are suggestive of a dose-dependent effect. No unexpected tolerability findings were noted.</p> |
| first_indexed | 2024-12-11T10:54:21Z |
| format | Article |
| id | doaj.art-c184ec3574f146a5b85139d990f03a90 |
| institution | Directory Open Access Journal |
| issn | 1744-859X |
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| publishDate | 2011-04-01 |
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| spelling | doaj.art-c184ec3574f146a5b85139d990f03a902022-12-22T01:10:10ZengBMCAnnals of General Psychiatry1744-859X2011-04-011011210.1186/1744-859X-10-12Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trialMa Yi-WenSliwa Jennifer KBossie Cynthia AAlphs LarryTurner Norris<p>Abstract</p> <p>Background</p> <p>This post hoc analysis (trial registration: ClinicalTrials.gov NCT00590577) assessed onset of efficacy and tolerability of acute treatment with once-monthly paliperidone palmitate (PP), a long-acting atypical antipsychotic initiated by day 1 and day 8 injections, in a markedly to severely ill schizophrenia population.</p> <p>Methods</p> <p>Subjects entering the 13-week, double-blind trial were randomized to PP (39, 156, or 234 mg [25, 100, and 150 mg eq of paliperidone, respectively]) or placebo. This subgroup analysis included those with a baseline Clinical Global Impressions-Severity (CGI-S) score indicating marked to severe illness. PP subjects received a 234-mg day 1 injection (deltoid), followed by their assigned dose on day 8 and monthly thereafter (deltoid or gluteal). Thus, data for PP groups were pooled for days 4 and 8. Measures included Positive and Negative Syndrome Scale (PANSS), CGI-S, Personal and Social Performance (PSP), and adverse events (AEs). Analysis of covariance (ANCOVA) and last-observation-carried-forward (LOCF) methodologies, without multiplicity adjustments, were used to assess changes in continuous measures. Onset of efficacy was defined as the first time point a treatment group showed significant PANSS improvement (assessed days 4, 8, 22, 36, 64, and 92) versus placebo, which was maintained through end point.</p> <p>Results</p> <p>A total of 312 subjects met inclusion criterion for this subgroup analysis. After the day 1 injection, mean PANSS total scores improved significantly with PP (all received 234 mg) versus placebo at day 4 (<it>P </it>= 0.012) and day 8 (<it>P </it>= 0.007). After the day 8 injection, a significant PANSS improvement persisted at all subsequent time points in the 234-mg group versus placebo (<it>P </it>< 0.05). PANSS improvements were greater from day 36 through end point in the 156-mg group (<it>P </it>< 0.05) and only at end point in the 39-mg group (<it>P </it>< 0.05). CGI-S and PSP scores improved significantly in the 234-mg and 156-mg PP groups versus placebo at end point (<it>P </it>< 0.05 for both, respectively); improvement in the 39-mg group was not significant. The most common AEs for PP-treated subjects (≥10%, any treatment group) were headache, insomnia, schizophrenia exacerbation, injection site pain, and agitation.</p> <p>Conclusions</p> <p>In this markedly to severely ill population, acute treatment with 234 mg PP improved psychotic symptoms compared with placebo by day 4. After subsequent injections, observed improvements are suggestive of a dose-dependent effect. No unexpected tolerability findings were noted.</p>http://www.annals-general-psychiatry.com/content/10/1/12 |
| spellingShingle | Ma Yi-Wen Sliwa Jennifer K Bossie Cynthia A Alphs Larry Turner Norris Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial Annals of General Psychiatry |
| title | Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial |
| title_full | Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial |
| title_fullStr | Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial |
| title_full_unstemmed | Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial |
| title_short | Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial |
| title_sort | onset of efficacy with acute long acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia post hoc analysis of a randomized double blind clinical trial |
| url | http://www.annals-general-psychiatry.com/content/10/1/12 |
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