Paliperidone palmitate and risperidone long-acting injectable in subjects with schizophrenia recently treated with oral risperidone or other oral antipsychotics

Figures & data

Table 1 Baseline demographics and clinical characteristics

	Paliperidone palmitate			RLAI
	Prior Ris only (n = 126)	Prior other APa (n = 199)	No prior AP (n = 56)	Prior Ris only (n = 107)	Prior other APa (n = 203)	No prior AP (n = 56)
Age, years, mean (SD)	38.8 (11.5)	40.2 (11.5)	39.0 (11.8)	38.4 (11.0)	39.4 (12.6)	37.9 (10.9)
Gender, n (%)
Male	77 (61.1)	104 (52.3)	41 (73.2)	56 (52.3)	110 (54.2)	28 (50.0)
Female	49 (38.9)	95 (47.7)	15 (26.8)	51 (47.7)	93 (45.8)	28 (50.0)
Race, n (%)
Caucasian	109 (86.5)	158 (79.4)	41 (73.2)	95 (88.8)	161 (79.3)	43 (76.8)
African American	12 (9.5)	20 (10.1)	10 (17.9)	6 (5.6)	22 (10.8)	10 (17.9)
Asian	5 (4.0)	20 (10.1)	5 (8.9)	6 (5.6)	20 (9.9)	1 (1.8)
Other	0	1 (0.5)	0	0	0	2 (3.6)
Age at diagnosis, years, mean (SD)	28.3 (8.2)	27.6 (9.2)	26.3 (8.6)	29.2 (9.1)	27.9 (9.5)	26.4 (8.2)
Previous hospitalizations, n (%)
0	10 (7.9)	23 (11.6)	8 (14.3)	14 (13.1)	22 (10.8)	4 (7.1)
1	20 (15.9)	45 (22.6)	9 (16.1)	24 (22.4)	49 (24.1)	11 (19.6)
2	21 (16.7)	30 (15.1)	9 (16.1)	19 (17.8)	34 (16.7)	8 (14.3)
3	27 (21.4)	23 (11.6)	6 (10.7)	17 (15.9)	26 (12.8)	10 (17.9)
≥4	48 (38.1)	78 (39.2)	24 (42.9)	33 (30.8)	72 (35.5)	23 (41.1)

Notes:

a The “Prior other AP” group includes patients who received the following medications within 2 weeks before start of double-blind study medication: amisulpride, aripiprazole, chlorpromazine, chlorprothixene, clotiapine, flupentixol, fluphenazine, haloperidol, haloperidol decanoate, levomepromazine, loxapine, melperone, olanzapine, perazine, perphenazine, promazine, promethazine, quetiapine, risperidone (included because it was not the only antipsychotic used in this population), sertindole, sulpiride, and thioridazine.

Abbreviations: AP, antipsychotic; Ris, risperidone; RLAI, risperidone long-acting injectable; SD, standard deviation.

Table 2 Patient disposition and study medication exposure

	Paliperidone palmitate			RLAI
	Prior Ris only (n = 126)	Prior other APa (n = 199)	No prior AP (n = 56)	Prior Ris only (n = 107)	Prior other APa (n = 203)	No prior AP (n = 56)
Disposition
Completed, n (%)	111 (88.1)	166 (83.4)	44 (78.6)	93 (86.9)	171 (84.2)	46 (82.1)
Discontinued, n (%)	15 (11.9)	33 (16.6)	12 (21.4)	14 (13.1)	32 (15.8)	10 (17.9)
Lack of efficacy	1 (0.8)	15 (7.5)	1 (1.8)	4 (3.7)	13 (6.4)	1 (1.8)
Withdrew consent	8 (6.3)	10 (5.0)	2 (3.6)	6 (5.6)	12 (5.9)	3 (5.4)
AE	1 (0.8)	5 (2.5)	0	0	2 (1.0)	2 (3.6)
Lost to follow-up	1 (0.8)	2 (1.0)	4 (7.1)	1 (0.9)	2 (1.0)	2 (3.6)
Death	0	0	1 (1.8)	0	0	0
Other	4 (3.2)	1 (0.5)	4 (7.1)	3 (2.8)	3 (1.5)	2 (3.6)
Study medication exposure
Mean dose, mean (SD), mg	115.8 (7.2)	115.2 (7.7)	114.8 (6.5)	28.5 (4.9)	28.2 (4.6)	27.4 (4.2)
Final dose, mean (SD), mg	112.3 (24.2)	109.8 (23.9)	106.3 (21.5)	31.9 (9.6)	31.5 (9.2)	29.7 (8.1)
Total exposure, mean (SD), days	88.3 (12.0)	87.1 (14.2)	86.2 (15.3)	88.1 (13.4)	86.6 (14.7)	84.9 (17.2)

Notes:

a The “Prior other AP” group includes patients who received the following medications within 2 weeks before start of double-blind study medication: amisulpride, aripiprazole, chlorpromazine, chlorprothixene, clotiapine, flupentixol, fluphenazine, haloperidol, haloperidol decanoate, levomepromazine, loxapine, melperone, olanzapine, perazine, perphenazine, promazine, promethazine, quetiapine, risperidone (included because it was not the only antipsychotic used in this population), sertindole, sulpiride, and thioridazine.

Abbreviations: AE, adverse event; AP, antipsychotic; Ris, risperidone; RLAI, risperidone long-acting injectable; SD, standard deviation.

Figure 1 Categorical CGI-S scores from baseline to end point.

Abbreviations: AP, antipsychotic; BL, baseline; CGI-S, Clinical Global Impression–Severity scale; EP, end point; Ris, risperidone; RLAI, risperidone long-acting injectable.

Table 3 Efficacy outcomes

	Paliperidone palmitate			RLAI
	Prior Ris only (n = 126)	Prior other APa (n = 199)	No prior AP (n = 56)	Prior Ris only (n = 107)	Prior other APa (n = 203)	No prior AP (n = 56)
PANSS total, mean (SD)
Baseline	84.3 (11.2)	85.3 (11.7)	84.9 (12.1)	83.7 (10.4)	83.2 (10.9)	83.9 (11.3)
Change from baseline to end point	−18.7 (13.7)b	−18.5 (17.3)b	−19.5 (12.8)b	−18.3 (13.2)b	−17.6 (14.1)b	−17.5 (16.1)b
PANSS positive symptoms, mean (SD)
Baseline	23.3 (4.5)	24.3 (4.8)	24.4 (4.3)	23.8 (4.6)	23.6 (4.5)	24.1 (4.4)
Change from baseline to end point	−5.6 (4.8)b	−6.2 (5.8)b	−6.2 (4.5)b	−5.8 (4.7)b	−5.7 (4.8)b	−5.9 (4.9)b
PANSS negative symptoms, mean (SD)
Baseline	22.7 (4.6)	22.2 (4.6)	21.4 (5.2)	22.0 (4.7)	21.8 (4.4)	21.2 (4.6)
Change from baseline to end point	−4.6 (3.8)b	−4.0 (5.2)b	−3.9 (3.8)b	−4.0 (4.3)b	−4.2 (4.2)b	−3.6 (4.8)b
PANSS disorganized thought, mean (SD)
Baseline	19.9 (3.8)	20.3 (3.7)	19.6 (3.9)	19.8 (3.7)	19.7 (3.7)	19.4 (3.5)
Change from baseline to end point	−3.7 (3.6)b	−3.5 (4.4)b	−4.1 (3.6)b	−4.0 (3.5)b	−3.4 (3.5)b	−3.0 (4.5)b
PANSS uncontrolled hostility/excitement, mean (SD)
Baseline	8.5 (2.9)	8.5 (3.0)	8.8 (2.8)	8.4 (2.7)	8.2 (3.0)	8.9 (2.8)
Change from baseline to end point	−1.9 (2.8)b	−1.9 (3.0)b	−1.9 (2.4)b	−2.1 (2.4)b	−1.6 (3.0)b	−1.7 (3.1)b
PANSS anxiety/depression, mean (SD)
Baseline	9.9 (2.5)	10.1 (2.7)	10.6 (2.2)	9.7 (2.7)	9.8 (2.5)	10.3 (2.4)
Change from baseline to end point	−3.0 (2.5)b	−2.8 (3.3)b	−3.4 (2.8)b	−2.4 (2.5)b	−2.6 (2.8)b	−3.4 (2.6)b
CGI-S, mean (SD)
Baseline	4.2 (0.6)	4.3 (0.6)	4.3 (0.8)	4.2 (0.7)	4.2 (0.7)	4.2 (0.6)
Change from baseline to end point	−1.0 (0.9)b	−1.0 (1.0)b	−1.1 (0.9)b	−1.0 (0.9)b	−0.9 (0.9)b	−0.9 (0.9)b
PSP, mean (SD)
Baseline	55.5 (12.6)	52.8 (11.7)	56.6 (12.5)	55.7 (11.1)	54.5 (12.6)	56.9 (12.0)
Change from baseline to end point	9.9 (10.5)b	9.7 (11.8)b	8.6 (10.7)b	9.9 (10.7)b	9.2 (11.2)b	10.5 (10.5)b
Responder rate at end pointc, n (%)	72 (57.1)	107 (53.8)	37 (66.1)	56 (52.3)	108 (53.2)	27 (48.2)

Notes:

a The “Prior other AP” group includes patients who received the following medications within 2 weeks before start of double-blind study medication: amisulpride, aripiprazole, chlorpromazine, chlorprothixene, clotiapine, flupentixol, fluphenazine, haloperidol, haloperidol decanoate, levomepromazine, loxapine, melperone, olanzapine, perazine, perphenazine, promazine, promethazine, quetiapine, risperidone (included because it was not the only antipsychotic used in this population), sertindole, sulpiride, and thioridazine;

b P ≤ 0.0002, baseline to end point;

c proportion of subjects with ≥30% improvement at end point in PANSS total score.

Abbreviations: AP, antipsychotic; CGI-S, Clinical Global Impressions–Severity scale; PANSS, Positive and Negative Syndrome Scale; PSP, Personal and Social Performance scale; Ris, risperidone; RLAI, risperidone long-acting injectable; SD, standard deviation.

Figure 2 Categorical PSP scale score from baseline to end point.

Abbreviations: AP, antipsychotic; BL, baseline; PSP, Personal and Social Performance; EP, end point; Ris, risperidone; RLAI, risperidone long-acting injectable.

Table 4 Treatment-emergent adverse events

	Paliperidone palmitate			RLAI
n (%)	Prior Ris only (n = 126)	Prior other APa (n = 199)	No prior AP (n = 56)	Prior Ris only (n = 107)	Prior other APa (n = 203)	No prior AP (n = 56)
Subjects with ≥1 AE	68 (54.0)	122 (61.3)	31 (55.4)	56 (52.3)	109 (53.7)	29 (51.8)
Discontinuation due to AEs	1 (0.8)	5 (2.5)	0	0	2 (1.0)	2 (3.6)
Most common AEs (≥5% in any group)
Headache	8 (6.3)	18 (9.0)	5 (8.9)	6 (5.6)	19 (9.4)	3 (5.4)
Insomnia	13 (10.3)	25 (12.6)	4 (7.1)	6 (5.6)	17 (8.4)	4 (7.1)
Injection site pain	9 (7.1)	6 (3.0)	6 (10.7)	0	2 (1.0)	0
Somnolence	5 (4.0)	12 (6.0)	3 (5.4)	6 (5.6)	7 (3.4)	1 (1.8)
Akathisia	5 (4.0)	13 (6.5)	3 (5.4)	4 (3.7)	7 (3.4)	1 (1.8)
Schizophrenia	3 (2.4)	11 (5.5)	1 (1.8)	3 (2.8)	7 (3.4)	2 (3.6)
Salivary hypersecretion	1 (0.8)	7 (3.5)	3 (5.4)	3 (2.8)	0	1 (1.8)
Weight increased	5 (4.0)	3 (1.5)	3 (5.4)	2 (1.9)	3 (1.5)	3 (5.4)
Nasopharyngitis	2 (1.6)	5 (2.5)	2 (3.6)	2 (1.9)	4 (2.0)	3 (5.4)
Lethargy	2 (1.6)	2 (1.0)	0	0	0	4 (7.1)
Tremor	0	8 (4)	3 (5.4)	2 (1.9)	5 (2.5)	0
Subjects with ≥1 EPS-related AE	10 (7.9)	31 (15.6)	9 (16.1)	9 (8.4)	22 (10.8)	2 (3.6)
Most common EPS-related AEs (≥2% in any group)
Akathisia	5 (4.0)	13 (6.5)	3 (5.4)	4 (3.7)	7 (3.4)	1 (1.8)
Muscle rigidity	2 (1.6)	3 (1.5)	1 (1.8)	3 (2.8)	3 (1.5)	0
Muscle tightness	0	1 (0.5)	2 (3.6)	0	1 (0.5)	0
Musculoskeletal stiffness	2 (1.6)	1 (0.5)	2 (3.6)	1 (0.9)	0	0
Tremor	0	8 (4.0)	3 (5.4)	2 (1.9)	5 (2.5)	0
Parkinsonism	0	5 (2.5)	1 (1.8)	0	2 (1.0)	0
Subjects with ≥1 prolactin-related AE	2 (1.6)	6 (3.0)	2 (3.6)	2 (1.9)	5 (2.5)	4 (7.1)
Most common prolactin-related AEs (≥1% in any group)
Amenorrhea	0	2 (1.0)	1 (1.8)	1 (0.9)	2 (1.0)	1 (1.8)
Anorgasmia	0	1 (0.5)	0	0	0	1 (1.8)
Erectile dysfunction	1 (0.8)	0	0	1 (0.9)	1 (0.5)	1 (1.8)
Galactorrhea	0	0	0	0	0	1 (1.8)
Ejaculation delayed	0	0	1 (1.8)	0	0	0
Libido decreased	1 (0.8)	2 (1.0)	0	0	1 (0.5)	0
Subjects with ≥1 glucose-related AE	0	1 (0.5)b	0	0	0	0

Notes:

a The “Prior other AP” group includes patients who received the following medications within 2 weeks before start of double-blind study medication: amisulpride, aripiprazole, chlorpromazine, chlorprothixene, clotiapine, flupentixol, fluphenazine, haloperidol, haloperidol decanoate, levomepromazine, loxapine, melperone, olanzapine, perazine, perphenazine, promazine, promethazine, quetiapine, risperidone (included because it was not the only antipsychotic used in this population), sertindole, sulpiride, and thioridazine;

b one subject had an increased blood glucose level.

Abbreviations: AE, adverse event; AP, antipsychotic; EPS, extrapyramidal symptom; Ris, risperidone; RLAI, risperidone long-acting injectable.