Safety and efficacy of different initial doses of lurasidone in the schizophrenia treatment: A multi-center, randomized, open-label study

Table 1 Patient demographic and clinical characteristics at baseline (full analysis set), mean ± SD/n (%)

Characteristic	Lurasidone (40 mg/day), n = 99	Lurasidone (80 mg/day), n = 98	Overall, n = 197
Age (years)	35.7 ± 12.13	34.1 ± 11.15	34.9 ± 11.65
Male	37 (37.4)	29 (29.6)	66 (33.5)
Female	62 (62.6)	69 (70.4)	131 (66.5)
Body weight (kg)	64.98 ± 18.50	61.04 ± 12.21	63.02 ± 15.77
BMI (kg/m2)	23.89 ± 5.87	22.97 ± 4.30	23.43 ± 5.16
PANSS total score	86.5 ± 11.93	87.7 ± 12.03	87.1 ± 11.96
CGI-S score
4 points	12 (12.1)	18 (18.4)	30 (15.2)
5 points	60 (60.6)	61 (62.2)	121 (61.4)
6 points	26 (26.3)	16 (16.3)	42 (21.3)
7 points	1 (1.0)	3 (3.1)	4 (2.0)
CDSS score	3.0 ± 3.98	2.5 ± 3.91	2.8 ± 3.94
AIMS total score	0.1 ± 0.38	0.1 ± 1.11	0.1 ± 0.83
BARS score
0 points	85 (85.9)	90 (91.8)	175 (88.8)
1 point	4 (4.0)	2 (2.0)	6 (3.0)
2 points	7 (7.1)	4 (4.1)	11 (5.6)
3 points	1 (1.0)	2 (2.0)	3 (1.5)
4 points	2 (2.0)	0 (0)	2 (1.0)
SAS total score	0.4 ± 1.61	0.3 ± 0.99	0.3 ± 1.34
Prior antipsychotic medication	71 (71.7)	77 (78.6)	148 (75.1)
Number of episodes	2.7 ± 5.04	2.8 ± 3.52	2.8 ± 4.34

BMI: Body mass index; PANSS: Positive and Negative Syndrome Scale; CGI-S: Clinical Global Impression Scale-Severity; CDSS: Calgary Depression Scale for Schizophrenia; AIMS: Abnormal Involuntary Movement Scale; BARS: Barnes Akathisia Rating Scale; SAS: Self-Rating Anxiety Scale.

Table 2 Exposure and dose modification (full analysis set), mean ± SD

	Lurasidone (40 mg/day), n = 99	Lurasidone (80 mg/day), n = 98	Overall, n = 197
Exposure days on drug (day)	38.6 ± 9.16	32.7 ± 14.55	35.7 ± 12.46
Total exposure level (mg)	2436.4 ± 803.89	2492.0 ± 1147.47	2464.1 ± 987.69
Average daily dose (mg/day)	62.45 ± 13.62	76.72 ± 8.58	69.55 ± 13.43
Dose modification during the second week (%)	60.6	8.2	34.5

Table 3 Summary of adverse events and adverse reactions (safety set), n (%), events

Category	Lurasidone (40 mg/day), n = 99	Lurasidone (80 mg/day), n = 98
Treatment-emergent adverse events	64 (64.6), 182	70 (71.4), 178
Serious adverse events (during the treatment)	1 (1.0), 1	4 (4.1), 4
Adverse reactions	53 (53.5), 122	56 (57.1), 115
Serious adverse reactions (during the treatment)	1 (1.0), 1	3 (3.1), 3
Adverse events leading to discontinuation of investigational product	3 (3.0), 3	5 (5.1), 5
Adverse events leading to dose reduction of investigational product	4 (4.0), 7	12 (12.2), 16
Adverse events leading to subject withdrawal from the trial	1 (1.0), 1	2 (2.0), 2
Adverse events leading to subject death	0, 0	0, 0

Table 4 Change from baseline to endpoint for weight (safety set), n (%)

Measure		Lurasidone (40 mg/day), n = 99	Lurasidone (80 mg/day), n = 98
Weight, kg	Baseline, mean (SD)	64.98 (18.50)	61.04 (12.21)
	Mean change (SD)	0.83 (2.83)a	-0.08 (2.22)
	≥ 7% weight gain	12 (12.1)	4 (4.1)
	≥ 7% weight loss	3 (3.0)	4 (4.1)
BMI (kg/m2)	Baseline, mean (SD)	23.89 (5.87)	22.97 (4.30)
	Mean change (SD)	0.30 (1.06)a	-0.01 (0.86)
	≥ 7% BMI gain	12 (12.1)	4 (4.1)
	≥ 7% BMI loss	3 (3.0)	4 (4.1)

^aP < 0.01 vs baseline.

BMI: Body mass index.

Table 5 Change from baseline to Visit 1-4 for efficacy measures (full analysis set and mixed model for repeated measurements analysis)

Scale	Visit	LS mean (SE)		Difference between groups
		Lurasidone (40 mg/day), n = 99	Lurasidone (80 mg/day), n = 98	LS difference (SE)	95%CI	P value1	P value2
PANSS total	Visit 1	-14.3 (1.41)	-17.0 (1.47)	2.7 (2.04)	-1.30 to 6.73	0.183	0.273
	Visit 2	-20.9 (1.64)	-25.4 (1.72)	4.5 (2.38)	-0.18 to 9.20	0.060	0.114
	Visit 3	-26.4 (1.81)	-30.6 (1.93)	4.2 (2.65)	-1.04 to 9.41	0.116	0.176
	Visit 4	-30.6 (1.92)	-34.2 (2.08)	3.7 (2.84)	-1.93 to 9.27	0.198	0.254
PANSS positive subscale	Visit 1	-4.1 (0.46)	-5.6 (0.48)	1.6 (0.67)	0.23-2.88	0.022a	0.143
	Visit 2	-6.7 (0.49)	-8.4 (0.52)	1.7 (0.72)	0.25-3.08	0.022a	0.063
	Visit 3	-8.6 (0.57)	-9.5 (0.61)	0.9 (0.83)	-0.77 to 2.52	0.294	0.581
	Visit 4	-9.7 (0.60)	-10.4 (0.65)	0.7 (0.88)	-1.02 to 2.46	0.416	0.708
PANSS negative subscale	Visit 1	-3.4 (0.43)	-3.5 (0.45)	0.1 (0.63)	-1.15 to 1.31	0.899	0.742
	Visit 2	-4.6 (0.52)	-5.8 (0.54)	1.2 (0.75)	-0.26 to 2.71	0.105	0.039
	Visit 3	-5.5 (0.56)	-6.7 (0.60)	1.3 (0.82)	-0.37 to 2.89	0.128	0.194
	Visit 4	-6.5 (0.62)	-8.2 (0.66)	1.7 (0.91)	-0.10 to 3.48	0.064	0.145
PANSS general psychopathology subscale	Visit 1	-6.8 (0.70)	-8.0 (0.73)	1.2 (1.01)	-0.80 to 3.19	0.239	0.298
	Visit 2	-9.5 (0.86)	-11.3 (0.90)	1.7 (1.24)	-0.74 to 4.16	0.169	0.424
	Visit 3	-12.3 (0.90)	-14.4 (0.96)	2.0 (1.32)	-0.55 to 4.65	0.121	0.225
	Visit 4	-14.3 (0.90)	-15.6 (0.98)	1.2 (1.33)	-1.39 to 3.87	0.353	0.446
Positive factor score	Visit 1	-2.3 (0.28)	-3.0 (0.29)	0.7 (0.40)	-0.06 to 1.52	0.071	0.599
	Visit 2	-4.0 (0.31)	-5.0 (0.33)	1.0 (0.45)	0.14-1.92	0.024a	0.199
	Visit 3	-5.3 (0.37)	-5.7 (0.40)	0.4 (0.55)	-0.64 to 1.53	0.419	0.923
	Visit 4	-6.1 (0.38)	-6.3 (0.42)	0.2 (0.57)	-0.94 to 1.30	0.754	0.672
Negative factor score	Visit 1	-3.3 (0.42)	-3.1 (0.44)	-0.2 (0.61)	-1.42 to 0.99	0.727	0.932
	Visit 2	-3.9 (0.52)	-5.0 (0.54)	1.1 (0.75)	-0.42 to 2.54	0.161	0.065
	Visit 3	-4.9 (0.56)	-5.9 (0.59)	1.0 (0.82)	-0.61 to 2.61	0.222	0.242
	Visit 4	-5.9 (0.59)	-7.4 (0.63)	1.5 (0.87)	-0.20 to 3.23	0.082	0.155
Cognitive scale score	Visit 1	-1.1 (0.20)	-1.6 (0.20)	0.6 (0.28)	-0.01 to 1.11	0.054	0.029a
	Visit 2	-1.8 (0.23)	-2.6 (0.24)	0.8 (0.33)	0.14-1.44	0.018a	0.008a
	Visit 3	-2.1 (0.24)	-3.2 (0.25)	1.1 (0.35)	0.38-1.76	0.002a	0.003a
	Visit 4	-2.4 (0.24)	-3.5 (0.26)	1.1 (0.36)	0.38-1.80	0.003a	0.003a
Excitation scale score	Visit 1	-2.1 (0.31)	-3.1 (0.33)	1.0 (0.45)	0.07-1.85	0.035a	0.119a
	Visit 2	-2.9 (0.31)	-3.8 (0.33)	0.9 (0.45)	0.00-1.79	0.051	0.168
	Visit 3	-3.6 (0.26)	-4.4 (0.28)	0.8 (0.38)	0.04-1.56	0.040a	0.274
	Visit 4	-3.7 (0.34)	-4.2 (0.37)	0.5 (0.50)	-0.50 to 1.48	0.330	0.326
Depression and anxiety scale score	Visit 1	-1.2 (0.16)	-1.3 (0.17)	0.1 (0.23)	-0.32 to 0.60	0.551	0.878
	Visit 2	-1.7 (0.18)	-1.6 (0.19)	-0.1 (0.27)	-0.60 to 0.45	0.781	0.517
	Visit 3	-2.1 (0.18)	-2.0 (0.20)	-0.1 (0.27)	-0.64 to 0.43	0.698	0.384
	Visit 4	-2.2 (0.19)	-2.0 (0.21)	-0.2 (0.28)	-0.76 to 0.34	0.451	0.226
CGI-S	Visit 1	-0.6 (0.12)	-0.9 (0.12)	0.2 (0.17)	-0.10 to 0.57	0.165	0.525
	Visit 2	-1.0 (0.11)	-1.4 (0.12)	0.3 (0.16)	0.01-0.66	0.044a	0.433
	Visit 3	-1.6 (0.13)	-1.8 (0.14)	0.3 (0.19)	-0.12 to 0.64	0.178	0.721
	Visit 4	-1.9 (0.14)	-2.1 (0.15)	0.2 (0.20)	-0.19 to 0.62	0.298	0.920
CDSS	Visit 1	-1.5 (0.20)	-1.2 (0.21)	-0.4 (0.29)	-0.95 to 0.21	0.213	0.029a
	Visit 2	-1.9 (0.22)	-1.3 (0.23)	-0.6 (0.32)	-1.22 to 0.05	0.072	0.050
	Visit 3	-2.0 (0.22)	-1.5 (0.24)	-0.5 (0.33)	-1.13 to 0.16	0.142	0.035a
	Visit 4	-2.3 (0.22)	-1.4 (0.24)	-0.9 (0.32)	-1.52 to -0.25	0.006a	0.031a

¹P values were derived from the Mixed Model for Repeated Measures model, in which fixed effects included treatment, visit, and treatment-visit interaction effects. Covariates were the baseline values, and random effects were the participants.

²P values were used to compare differences in change from baseline between the two groups at each visit point using either a paired t-test or Wilcoxon paired signed-ranks test. Missing values were imputed using the last observation carried forward approach.

^aP < 0.05 vs lurasidone (40 mg/day).

PANSS: Positive and Negative Syndrome Scale; CGI-S: Clinical Global Impression Scale-Severity; CDSS: Calgary Depression Scale for Schizophrenia; LS: Least squares; CI: Confidence interval; SE: Standard error.