Paliperidone ER: Reformulated antipsychotic for schizophrenia Tx

Current Psychiatry. 2007 September;06(09):75-82

September 1, 2007|Psychiatry

Jeffrey Rado, MD;Sheila M. Dowd, PhD;Philip G. Janicak, MD

Risperidone’s metabolite behaves well but differently in once-daily delivery.

Patients taking either paliperidone ER dose showed statistically significant greater improvement in PANSS total score compared with those taking placebo (6 mg, P = 0.006; 12 mg, P

Clinical response rates were similar with the 6-mg and 12-mg paliperidone ER doses—50% and 51%, respectively—and greater than with placebo (34%). The higher response rates with paliperidone ER were statistically significant compared with placebo (6 mg, P

Discontinuation rates for lack of efficacy were lower with paliperidone ER (6 mg, 23%; 12 mg, 14%) than with placebo (35%). A substantially lower percentage of patients taking this agent remained classified as “marked/severe/extremely severe” on the CGI-S score from baseline to endpoint, compared with the placebo group;

6 mg paliperidone ER, 58% to 26%
12 mg paliperidone ER, 64% to 21%
placebo, 60% to 45%.

PSP scores improved in both paliperidone ER groups, but the difference compared with placebo was statistically significant only for the 6-mg dose (P

The second study² included U.S. and international sites and compared 3 fixed doses of paliperidone ER (6-, 9-, and 12-mg) with placebo. Among the 630 patients enrolled, 66% completed the study. Patients were randomly assigned to 6 mg, 9 mg, or 12 mg of paliperidone ER; 10 mg of olanzapine; or placebo. The number of patients who dropped out because of adverse events was comparable across the groups.

Patient groups assigned to paliperidone ER showed significant improvement when compared with placebo (P 30% reduction in PANSS total score from baseline to endpoint included:

6 mg paliperidone ER, 56%
9 mg paliperidone ER, 51%
12 mg paliperidone ER, 61%
placebo, 30%.

Discontinuation rates for lack of efficacy also were lower in the paliperidone ER groups vs placebo (6 mg, 16%; 9 mg, 16%; 12 mg, 10%; placebo, 40%). A substantially lower percentage of patients taking the drug remained classified as “marked/severe/extremely severe” by CGI-S score, compared with placebo:

6 mg paliperidone ER, 63% at baseline to 22% at endpoint
9 mg paliperidone ER, 58% to 23%
12 mg paliperidone ER, 64% to 16%
placebo, 60% to 51%.

PSP scores improved significantly for all 3 paliperidone ER doses vs placebo.

The third study³ was a multicenter international trial that compared 3 fixed doses of paliperidone ER (3, 9, and 15 mg) with placebo. Among the 618 randomized patients, 365 (59%) completed the study: 70 of 127 (55%) on 3-mg paliperidone ER, 78 of 125 (62%) on 9-mg paliperidone ER, 82 of 115 (71%) on 15-mg paliperidone ER, and 47 of 123 (38%) on placebo.

Clinical Point

In clinical trials, weight gain with paliperidone ER was similar to that seen with risperidone and in the moderate range among SGAs

All 3 paliperidone ER doses were associated with statistically significant improvements in PANSS total and Marder factor scores at endpoint compared with placebo (P

3 mg paliperidone ER, 40%
9 mg paliperidone ER, 46%
15 mg paliperidone ER, 53%
placebo, 18% (P ≤0.005).

Discontinuation rates for lack of efficacy were lower in the paliperidone ER groups vs placebo and were dose-related (3 mg, 24%; 9 mg, 18%; 15 mg, 12%; placebo, 44%). Among patients taking olanzapine, 10 mg, 13% discontinued for lack of efficacy. Substantially fewer patients in the active drug groups were classified as “marked/severe/extremely severe” from baseline to end-point on the CGI-S scale vs the placebo group:

3 mg paliperidone ER, 54% to 32%
9 mg paliperidone ER, 52% to 23%
15 mg paliperidone ER, 57% to 17%
placebo, 56% to 50%.

Finally, a statistically significant improvement in mean PSP scores from baseline to endpoint was seen for all 3 paliperidone ER doses vs placebo (3 mg, 8.3 ± 17 points; 9 mg, 7.6 ± 14 points; 15 mg, 12 ± 15.7 points; placebo, 1.5 ± 16 points [P

Additional trial evidence

Schizophrenia subpopulations. Post hoc analyses of data reported from the 3 pivotal trials suggest that paliperidone ER may be useful for specific groups of schizophrenia patients, including those who are recently diagnosed, age >65, or severely ill or have predominant negative symptoms or sleep problems (Table 4).^18-23

Clinical Point

Sleep quality improved without greater daytime sleepiness in stable patients with schizophrenia-related insomnia

So far, these analyses have been presented as posters at meetings or in sponsored supplements but have not been published in peer-reviewed publications.

Efficacy in delaying recurrence. Paliperidone ER’s efficacy in delaying symptom recurrence was examined in a randomized, double-blind, placebo-controlled study of 207 patients who had been stabilized on open-label, flexible-dosed paliperidone ER.²⁴ Time to first recurrence of schizophrenia symptoms was the primary efficacy measure. Starting dose was 9 mg/d (flexible dose range 3 to 15 mg/d).

References

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