Table 3.
Summary of efficacy studies for paliperidone palmitate
| Authors | Study details | Number of patients (n) | Length | Paliperidone palmitate dose and route |
Outcome | ||||
|---|---|---|---|---|---|---|---|---|---|
| Doses† (mg eq) | (mg) | route | |||||||
| Kramer et al14 | RCT, DB, PC Efficacy and safety study |
247 (197 ITT analysis) | 9 weeks | Gluteal | Mean PANSS total (SD) | ||||
| Baseline | Change from baseline | ||||||||
| 50 | 78 | 88.0 (12.39) | −5.2 (21.5) (P = 0.001)* | ||||||
| 100 | 156 | 85.2 (11.09) | −7.8 (19.4) (P < 0.001)* | ||||||
| Placebo | 87.8 (13.90) | 6.2 (18.3) | |||||||
| Gopal et al17 | RCT, DB, PC Dose-response study |
388 | 13 weeks | Gluteal | Mean PANSS total (SD) | ||||
| Baseline | Change from baseline | ||||||||
| 50 | 78 | 90 (10.8) | −3.5 (2.67) (P = 0.19) | ||||||
| 100 | 156 | 90 (11.7) | −6.9 (2.65) (P = 0.019)* | ||||||
| 150 | 234 | 92 (11.7) | −5.5 (3.61) | ||||||
| Placebo | 92 (12.6) | −4.1 (1.83) | |||||||
| Pandina et al18 | RCT, DB, PC Dose-response study |
652 | 13 weeks | Deltoid/gluteal | Mean PANSS total (SD) | Estimated effect sizes versus pbo | |||
| Baseline | Change from baseline | ||||||||
| 25 | 39 | 86.9 (11.99) | −8.1* | (0.28) | |||||
| 100 | 156 | 86.2 (10.77) | −11.6* | (0.49) | |||||
| 150 | 234 | 88.4 (11.70) | −13.2* | (0.55) | |||||
| Placebo | 86.8 (10.31) | −2.9 (*P ≤ 0.034) | |||||||
| Hough et al20 | RCT, DB, PC, study to evaluate efficacy in prevention of recurrence of symptoms | 312 included in the interim analysis 408 included in final analysis |
52 weeks | 25 | 39 | Gluteal | Time to relapse in PP patients versus placebo (P < 0.0001, Chi-square = 29.41) Relapse event rates: PP: 10% versus pbo: 34% Hazard ratio at final analysis (pbo/PP) was 3.60 (95% CI 2.45, 5.28) |
||
| 5 phases | 50 | 78 | |||||||
| 100 | 156 | ||||||||
| Gopal et al21 | Long-term, open-label, extension-phase study (see Hough et al20) | 388 | 52-week extension (median treatment duration 338 days) | Mode doses | OLE Baseline PANSS total score (SD) for total PP group: 58.1 (18.33) Mean (SD) of change from OLE baseline to endpoint in PANSS total score: −4.3 (15.43) Greatest improvement in PANSS total score was observed in PP pts who had been on pbo in DB phase: −8.4 (19.43) |
||||
| 100: 56% | 156 | ||||||||
| 50: 34% | 78 | ||||||||
| 75: 9% | 117 | ||||||||
| 25: 1% | 39 | ||||||||
| Poster presentations | |||||||||
| Nasrallah et al19,27 | RCT, DB, PC, parallelgroup, dose-response study | 518 (514 ITT population) | 13 weeks | Gluteal | Mean PANSS total (SD) | ||||
| Baseline | Change from baseline | ||||||||
| 25 | 39 | 90.7 (12.2) | −13.6 (21.45) (P = 0.02)* | ||||||
| 50 | 78 | 91.2 (12.0) | −13.2 (20.14) (P = 0.02)* | ||||||
| 100 | 156 | 90.8 (11.7) | −16.1 (20.36) (P < 0.001)* | ||||||
| Placebo | 90.7 (12.2) | −7.0 (20.07) | |||||||
| Comparison with RLAI | |||||||||
| Fleischhacker et al22 | RCT, parallel-group, noninferiority study of PP compared with RLAI | 749 | 53 weeks | PP: 39, 78, 117 or 156 mg/four weeks (+ oral pbo and IM pbo/two weeks) RLAI: 25, 37.5 or 50 mg/two weeks (+ oral risperidone) |
Mean (SD) change from baseline to endpoint (LOCF) in PANSS total (60–120 at baseline): PP: −12 (21.2) RLAI: −14 (19.8) Least-squares means change in PANSS total score was 2.6 points lower (95% CI 5.84, 0.61) for RLAI than PP group. Predetermined margin for noninferiority was not met (by 0.84 points). |
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| Pandina et al23 | RCT, DB, parallel-group, multicenter comparative study with RLAI | 1220 total 913 (ITT analysis) |
13 weeks | PP: 78, 156 or 234 mg/four weeks (+ oral pbo and IM pbo/two weeks) RLAI: 25, 37.5 or 50 mg/two weeks (+ oral risperidone) |
Baseline PANSS total score, mean (SD): PP: 84.1 (12.09); RLAI: 83.6 (11.28) Lower limit of 95% CI of treatment difference for change in PANSS total score exceeded protocol prespecified noninferiority margin (−5) PP demonstrated to be noninferior to RLAI (point estimate [95% CI]: 0.4 [−1.62; 2.38]) |
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*
Notes: Statistically significant;
†
Commercially available product dosage strengths of paliperidone palmitate are labeled in milligrams (mg) whereas current published poster presentations and clinical trials use doses reported as milligram equivalents (mg eq) to paliperidone.
Abbreviations: CI, confidence interval; DB, double-blind; ITT, intention to treat; LOCF, last observation carried forward; OLE, open label extension; Pp, paliperidone palmitate; pbo, placebo; PC, placebo-controlled; PANSS, positive and negative symptom scale; pts, patients; RCT, randomized controlled trial; RLAI, risperidone long-acting injection; SD, standard deviation.