Table 2.
Summary of TEAEs during (A) the DB trial and (B) the OLE study (safety population)
| (A) DB trial (Study 237) | |||
|---|---|---|---|
| TEAE category | Number of patients (%) | NNH (95% CI)a | |
| Lurasidone N = 391 |
Risperidone N = 190 |
||
| Any TEAE | 329 (84.1) | 160 (84.2) | |
| Most frequently reported TEAEsb | |||
| Insomnia | 60 (15.3) | 24 (12.6) | 37 (NS) |
| Nausea | 60 (15.3) | 20 (10.5) | 21 (NS) |
| Sedation | 54 (13.8) | 27 (14.2) | −251 (NS) |
| Akathisia | 53 (13.6) | 14 (7.4) | 17 (9, 87) |
| Somnolence | 53 (13.6) | 33 (17.4) | −27 (NS) |
| Headache | 38 (9.7) | 28 (14.7) | −20 (NS) |
| Weight increase | 38 (9.7) | 38 (20.0) | −10 (−26, −6) |
| Vomiting | 37 (9.5) | 7 (3.7) | 18 (11, 55) |
| Anxiety | 35 (9.0) | 16 (8.4) | 189 (NS) |
| Weight decrease | 29 (7.4) | 9 (4.7) | 38 (NS) |
| Dizziness | 24 (6.1) | 6 (3.2) | 34 (NS) |
| Nasopharyngitis | 21 (5.4) | 12 (6.3) | −106 (NS) |
| Psychotic disorder | 19 (4.9) | 13 (6.8) | −51 (NS) |
| Parkinsonism | 17 (4.3) | 10 (5.3) | −110 (NS) |
| Dystonia | 13 (3.3) | 12 (6.3) | −34 (NS) |
| Constipation | 7 (1.8) | 11 (5.8) | −26 (−234, −14) |
| Any EPS-related TEAEc | 48 (12.3) | 36 (18.9) | −15 (−457, −8) |
| Any metabolic-related TEAEd | 52 (13.3) | 43 (22.6) | −11 (−41, −7) |
| Any serious TEAE | 42 (10.7) | 17 (8.9) | 56 (NS) |
| Most frequently reported serious TEAEse | |||
| Psychotic disorder | 10 (2.6) | 8 (4.2) | −61 (NS) |
| Schizophrenia | 8 (2.0) | 2 (1.1) | 101 (NS) |
| Suicidal ideation | 2 (0.5) | 2 (1.1) | −185 (NS) |
| Any TEAE leading to discontinuation | 82 (21.0) | 27 (14.2) | 15 (8, 276) |
| Most frequently reported TEAEs leading to discontinuatione | |||
| Psychotic disorder | 13 (3.3) | 8 (4.2) | −113 (NS) |
| Schizophrenia | 12 (3.1) | 4 (2.1) | 104 (NS) |
| Suicidal ideation | 4 (1.0) | 2 (1.1) | −3377 (NS) |
| Akathisia | 4 (1.0) | 2 (1.1) | −3377 (NS) |
| Hallucination, auditory | 4 (1.0) | 0 | 98 (50, 3906) |
| Vomiting | 4 (1.0) | 0 | 98 (50, 3906) |
| Electrocardiogram QT prolonged | 0 | 2 (1.1) | −96 (NS) |
| (B) OLE study (Study 237-EXT) | ||
|---|---|---|
| TEAE category | Number of patients (%) | |
| Lurasidone–lurasidone N = 129 |
Risperidone–lurasidone N = 84 |
|
| Any TEAE | 76 (58.9) | 49 (58.3) |
| Most frequently reported TEAEsb | ||
| Headache | 6 (4.7) | 7 (8.3) |
| Psychotic disorder | 6 (4.7) | 6 (7.1) |
| Parkinsonism | 5 (3.9) | 5 (6.0) |
| Insomnia | 3 (2.3) | 5 (6.0) |
| Anxiety | 2 (1.6) | 6 (7.1) |
| Any EPS-related TEAEc | 11 (8.5) | 6 (7.1) |
| Any metabolic-related TEAEd | 4 (3.1) | 5 (6.0) |
| Any serious TEAE | 7 (5.4) | 3 (3.6) |
| Types of serious TEAE | ||
| Psychotic disorder | 2 (1.6) | 1 (1.2) |
| Schizophrenia | 1 (0.8) | 1 (1.2) |
| Completed suicide | 1 (0.8) | 0 |
| Ankle fracture | 1 (0.8) | 0 |
| Non-small cell lung cancer | 1 (0.8) | 0 |
| Convulsion | 1 (0.8) | 0 |
| Carbon monoxide poisoning | 0 | 1 (1.2) |
| Any TEAE leading to discontinuation | 7 (5.4) | 6 (7.1) |
| Most frequently reported TEAEs leading to discontinuatione | ||
| Psychotic disorder | 1 (0.8) | 2 (2.4) |
| Nausea | 0 | 1 (1.2) |
| Hepatitis C | 0 | 1 (1.2) |
| Anxiety | 0 | 1 (1.2) |
| Schizophrenia | 0 | 1 (1.2) |
aLurasidone versus risperidone. NNH is provided only for comparisons in which the 95% CI did not include infinity, denoting statistical significance at the p ≤ 0.05 threshold. NNH = 1/(rate with lurasidone − rate with risperidone) and rounded up. A negative NNH denotes an advantage for lurasidone relative to risperidone and can be expressed as a positive number if the comparison is risperidone vs lurasidone instead of lurasidone vs risperidone
b ≥ 5% of patients in either group
cEPS-related TEAEs were determined by medical review of preferred terms prior to unblinding in the DB trial and comprised: bradykinesia, cogwheel rigidity, drooling, dystonia, muscle rigidity, oculogyric crisis, oromandibular dystonia, parkinsonism, psychomotor retardation, torticollis, tremor, and trismus
dMetabolic-related TEAEs were determined by medical review of preferred terms prior to unblinding in the DB trial and comprised: increased blood glucose, increased blood triglycerides, diabetes mellitus, increased glycosylated haemoglobin, hyperglycaemia, hyperlipidaemia, hypertriglyceridaemia, metabolic syndrome, overweight, type 2 diabetes mellitus, and weight increase
e ≥ 1% of patients in either group
CI confidence interval, EPS extrapyramidal symptoms, NNH number needed to harm, NS not significant (the 95% CI contains infinity), TEAE treatment-emergent adverse event