Once-monthly paliperidone palmitate in recently diagnosed and chronic non-acute patients with schizophrenia

Figures & data

Table 1. Patient disposition.

	Recently diagnosed patients (≤3 years)	Chronic patients (>3 years)
Patients enrolled (n)	234	361
ITT population* (n)	233	360
	↓	↓
Most common reasons for early study discontinuation (≥2% in any group) (%)
Withdrawal of consent	6.4	12.5
Lost to follow-up	3.9	2.8
Adverse event	3.4	7.8
Lack of efficacy	3.0	2.2

*Patients who received at least one dose of study drug.

ITT: Intent-to-treat.

Table 2. Patient demographics and dosing information.

	Recently diagnosed (≤3 years) (n = 233)	Chronic (>3 years) (n = 360)
Mean age, years (SD)	32.2 (10.3)	42.4 (11.0)
Mean age at diagnosis, years (SD)	32.0 (10.3)	29.5 (9.4)
Male, (%)	63.9	62.5
Schizophrenia subtype, n (%)
Paranoid	195 (83.7)	271 (75.3)
Disorganized	13 (5.6)	30 (8.3)
Catatonic	1 (0.4)	4 (1.1)
Undifferentiated	19 (8.2)	35 (9.7)
Residual	5 (2.1)	20 (5.6)
Mean baseline weight, kg (SD)	77.6 (17.1)	83.3 (17.8)
Mean BMI, kg/m^2 (SD)	26.2 (5.7)	28.6 (5.9)
Patients with ≥1 co-morbidity, %*	60.9	61.4
Relevant co-morbidities reported in ≥5% of patients in any group and >4% difference between groups, n (%)
Metabolism and nutrition disorders	22 (9.4)	69 (19.2)
Vascular disorders	11 (4.7)	41 (11.4)
Hypertension	10 (4.3)	31 (8.6)
Number of patients with previous psychiatric hospitalizations, n (%)
None	59 (25.3)	54 (15.0)
1–3	135 (57.9)	120 (33.3)
≥4	39 (16.7)	186 (51.7)
PP1M dosing
Patients receiving PP1M initiation regimen at Day 1 and Day 8 according to protocol, n (%)^†	219 (94.0)	338 (93.9)
Mean modal PP1M maintenance dose, mg eq (SD)^‡	98.5 (34.2)	103.3 (32.9)
Last PP1M maintenance dose received, n (%) of patients
50 mg eq	26 (11.2)	27 (7.5)
75 mg eq	78 (33.5)	90 (25.0)
100 mg eq	71 (30.5)	140 (38.9)
150 mg eq	58 (24.9)	103 (28.6)
Relevant co-medications
Patients using benzodiazepines, n (%)
At baseline	43 (18.5)	95 (26.4)
Newly initiated during study	42 (18.0)	83 (23.1)
At endpoint	39 (16.7)	84 (23.3)
At 6 months for completers	25 (13.8)	60 (23.0)
Patients using anticholinergics, n (%)
At baseline	28 (12.0)	39 (10.8)
Newly initiated during study	22 (9.4)	26 (7.2)
At endpoint	18 (7.7)	28 (7.8)
At 6 months for completers	13 (7.2)	18 (6.9)

*Individual patients can be labelled for >1 co-morbidity.

^†The recommended initiation regimen was PP1M 150 mg eq on Day 1 and 100 mg eq on Day 8 given in the deltoid muscle.

^‡Excluding the initiation regimen (Day 1/Day 8).

BMI: body mass index; PP1M: once-monthly paliperidone palmitate; SD: standard deviation.

Figure 1. Mean PANSS total score over time (efficacy ITT population).

***p < 0.0001 vs. baseline.^†††p < 0.0001 for mean change from baseline in PANSS total score for recently diagnosed vs. chronic patients.Error bars represent 95% confidence intervals.BL: baseline; ITT: intent-to-treat; PANSS: Positive and Negative Syndrome Scale.

Table 3. Efficacy outcome (efficacy ITT population)*.

	Recently diagnosed (≤3 years) (n = 231)	Chronic (>3 years) (n = 358)
Mean PANSS positive subscale score, (SD)
Baseline	15.6 (4.8)	15.4 (5.0)
Endpoint	12.1 (4.7)	13.1 (5.4)
Mean change from baseline to endpoint	−3.6 (4.9)	−2.3 (4.9)
95% CI of mean change; p value^†	−4.2, −2.9; <0.0001	–2.8, −1.8; <0.0001
Change from baseline to endpoint p value between subgroup test^‡	0.0010
Mean PANSS negative subscale score, (SD)
Baseline	20.4 (5.3)	20.1 (5.5)
Endpoint	16.0 (5.5)	17.2 (6.1)
Mean change from baseline to endpoint	−4.4 (5.1)	−2.9 (5.5)
95% CI of mean change; p value^†	−5.1, −3.8; <0.0001	–3.4, −2.3; <0.0001
Change from baseline to endpoint p value between subgroup test^‡	0.0003
Mean PANSS general psychopathology score, (SD)
Baseline	36.6 (8.4)	35.2 (7.7)
Endpoint	29.5 (8.6)	30.8 (9.6)
Change from baseline to endpoint	−7.1 (8.4)	−4.4 (8.2)
95% CI of mean change; p value^†	−8.2, −6.0; <0.0001	−5.3, −3.6; <0.0001
Change from baseline to endpoint p value between subgroup test^‡	0.0001

*Only patients with a valid baseline measurement and at least one valid follow-up assessment were included.

^†Within-group difference was tested using the Wilcoxon signed-rank test.

^‡Between-group difference was tested using the Wilcoxon two-sample test.

CI: confidence interval; ITT: intent-to-treat; PANSS: Positive and Negative Syndrome Scale; SD: standard deviation.

Figure 2. CGI–C according to proportion of patients by category over time (efficacy ITT population).

*p = 0.0320; ^†p = 0.0008 between-group comparison, Fisher’s exact test.CGI–C: Clinical Global Impression–Change; ITT: intent-to-treat.

Table 4. Selected secondary endpoints*.

	Recently diagnosed (≤3 years)	Chronic (>3 years)
Mean SWN-S total score, n	211	310
Baseline, (SD)	80.7 (16.7)	79.7 (17.6)
Endpoint, (SD)	86.6 (17.7)	84.7 (17.1)
Mean change from baseline to endpoint, (SD)	5.9 (16.6)	5.0 (15.0)
95% CI; p value^†	3.6, 8.2; <0.0001	3.4, 6.7; <0.0001
Change from baseline to endpoint p value between subgroup test^‡	NS
Mean TSQM total global satisfaction score, n	195	299
Baseline, (SD)	56.6 (20.3)	55.4 (22.4)
Endpoint, (SD)	68.3 (23.4)	62.9 (26.0)
Mean change from baseline to endpoint (SD)	11.7 (27.9)	7.5 (29.7)
95% CI; p value^†	7.7, 15.6; <0.0001	4.1, 10.9; <0.0001
Change from baseline to endpoint p value between subgroup test^‡	NS
^§Mean quality of sleep score, n	229	353
Baseline, (SD)	6.9 (2.4)	6.7 (2.6)
Endpoint, (SD)	7.7 (2.2)	7.0 (2.4)
Mean change from baseline to endpoint, (SD)	0.8 (2.6)	0.3 (2.8)
95% CI; p value^†	0.5, 1.1; <0.0001	0.0, 0.6; 0.0346
Change from baseline to endpoint p value between subgroup test^‡	0.0397
^¶Mean drowsiness score, n	229	353
Baseline, (SD)	4.0 (2.8)	3.9 (2.9)
Endpoint, (SD)	2.8 (2.7)	3.3 (2.8)
Mean change from baseline to endpoint, (SD)	−1.3 (3.4)	−0.6 (3.4)
95% CI; p value^†	−1.7, −0.8; <0.0001	−1.0, −0.2; 0.0008
Change from baseline to endpoint p value between subgroup test^‡	0.0118

*Only patients with a valid baseline measurement and at least one valid follow-up assessment were included.

^†Within-group difference was tested using the Wilcoxon signed-rank test.

^‡Between-group difference was tested using the Wilcoxon two-sample test.

^§A higher score indicates improvements in the quality of sleep.

^¶A lower score indicates improvements in the level of drowsiness.

CI: confidence interval; NS: not significant; SD: standard deviation; SWN-S: Subjective Well-being under Neuroleptics (Short form); TSQM: Treatment Satisfaction Questionnaire for Medication.

Figure 3. Functioning outcomes in non-acute schizophrenia patients. Changes in frequency distribution by PSP category over time in recently diagnosed and chronic patients.

PSP: Personal and Social Performance

Figure 4. Functioning outcomes in non-acute schizophrenia patients: Mini-ICF-APP domain scores* at baseline and endpoint for recently diagnosed (A, n = 218) and chronic (B, n = 325) patients.

*Change from baseline to Month 6, p < 0.0001 for all domains in both groups.Mini-ICF-APP: Mini International Classification of Functionality, Disability and Health (ICF) Rating for Activity and Participation Disorders in Psychological Illnesses.

Table 5. TEAEs occurring in ≥5% of patients in any group (safety ITT population).

	Recently diagnosed (≤3 years) (n = 233)	Chronic (>3 years) (n = 360)
	Number of patients (%)
Injection-site pain	30 (12.9)	43 (11.9)
Insomnia	23 (9.9)	28 (7.8)
Anxiety	15 (6.4)	25 (6.9)
Headache	14 (6.0)	19 (5.3)
Akathisia	13 (5.6)	15 (4.2)
Somnolence	12 (5.2)	14 (3.9)
Weight increased	12 (5.2)	7 (1.9)
Depression	12 (5.2)	6 (1.7)
Psychotic disorder	11 (4.7)	25 (6.9)

ITT: intent-to-treat; TEAEs: treatment-emergent adverse events.