Table 4.
Safety Summary (Safety Population)
| Patients, n (%) | |||
|---|---|---|---|
| Aripiprazole | |||
| Low dose (n = 44) | High dose (n = 45) | Placebo (n = 44) | |
| Any patient with ≥1 adverse event | 29 (65.9) | 34 (75.6) | 18 (40.9) |
| Most common AEs (≥5% in any treatment group)a | |||
| Sedation | 8 (18.2) | 4 (8.9) | 1 (2.3) |
| Somnolence | 5 (11.4) | 7 (15.6) | 1 (2.3) |
| Increased appetite | 4 (9.1) | 3 (6.7) | 1 (2.3) |
| Fatigue | 3 (6.8) | 7 (15.6) | 0 |
| Headache | 3 (6.8) | 4 (8.9) | 1 (2.3) |
| Nausea | 3 (6.8) | 4 (8.9) | 1 (2.3) |
| Nasopharyngitis | 3 (6.8) | 4 (8.9) | 0 |
| Vomiting | 2 (4.5) | 3 (6.7) | 2 (4.5) |
| Lethargy | 0 | 5 (11.1) | 0 |
| Restlessness | 0 | 3 (6.7) | 1 (2.3) |
| Akathisia | 0 | 3 (6.7) | 0 |
| AEs leading to treatment discontinuationab | 1 (2.3) | 7 (15.6) | 1 (2.3) |
| Somnambulism | 1 (2.3) | 0 | 0 |
| Fatigue | 0 | 2 (4.4) | 0 |
| ECG QT prolonged | 0 | 1 (2.2) | 0 |
| Disturbance in attention | 0 | 1 (2.2) | 0 |
| Dysarthria | 0 | 1 (2.2) | 0 |
| Extrapyramidal disorder | 0 | 1 (2.2) | 0 |
| Headache | 0 | 1 (2.2) | 0 |
| Lethargy | 0 | 1 (2.2) | 0 |
| Somnolence | 0 | 1 (2.2) | 0 |
| Insomnia | 0 | 1 (2.2) | 0 |
| TD | 0 | 0 | 1 (2.3) |
| Extrapyramidal symptom and suicidal ideation assessments | n = 42 | n = 35 | n = 42 |
|---|---|---|---|
| LS mean (SE) change from baseline in AIMS score, week 8c | −3.45 (0.87) | −4.26 (0.87) | −1.99 (0.84) |
| Treatment difference vs. placebo (95% CI) | −1.46 (−3.57 to 0.65) | −2.27 (−4.42 to −0.13) | |
| p-Value | 0.1717 | 0.0382 | |
| LS mean (SE) change from baseline in BARS total score, week 8c | −0.18 (0.05) | −0.10 (0.05) | −0.09 (0.05) |
| Treatment difference vs. placebo (95% CI) | −0.09 (−0.20 to 0.03) | −0.01 (−0.13 to 0.12) | |
| p-Value | 0.1483 | 0.9090 | |
| LS mean (SE) change from baseline in SAS total score, week 8c | −0.28 (0.22) | −0.74 (0.22) | −0.10 (0.21) |
| Treatment difference vs. placebo (95% CI) | −0.18 (−0.77 to 0.41) | −0.64 (−1.24 to −0.04) | |
| p-Value | 0.5502 | 0.0357 | |
| Mean (SD) change from baseline in C-SSRS score, week 8d | −0.3 (1.5) | 0.1 (0.8) | 0 (0) |
AIMS scores range from 0 to 28, BARS total score ranges from 0 to 5, and SAS total score ranges from 0 to 40. Higher scores represent a worse condition, and a larger reduction from baseline represents greater improvement.
Suicidal ideation intensity total score is the sum of intensity scores ranging from 1 (least severe) to 5 (most severe) of five items (frequency, duration, controllability, deterrents, and reasons for ideation). A score of 0 is given if no suicidal ideation is reported for a total score ranging from 0 to 25.
By MedDRA Preferred term. Patients were counted once, per preferred term, for the most severe of multiple occurrences of a specific adverse event. Any patients with AEs in multiple system organ classes were counted once toward the total.
The patient in the low-dose aripiprazole group and six out of seven patients in the high-dose aripiprazole group who discontinued study medication because of AEs weighed <50 kg.
Number of patients with baseline and week 8 assessment (ITT population). Derived from a repeated-measures linear model with treatment, week, treatment by week interaction, region, and weight group as fixed categorical effects; the baseline value as a fixed covariate; and the week as the time variable for repeated measures.
Using suicidal ideation intensity total score.
AEs, adverse events; AIMS, Abnormal Involuntary Movement Scale; BARS, Barnes Akathisia Rating Scale; C-SSRS, Columbia-Suicide Severity Rating Scale; ECG, electrocardiogram; ITT, intent-to-treat; LS, least squares; SAS, Simpson-Angus Scale; SD, standard deviation; SE, standard error; TD, Tourette's disorder.