Of 258 subjects screened, 227 were randomized, with 170 in the BoNTA group and 57 in the placebo group; 222 completed the study. Reasons for discontinuation included SAEs (one breast cancer and one gastric cancer) that the investigator considered to be unrelated to the treatment, withdrawal from the study (n=2), and loss to follow-up (n=1). Overall, the mean age was 42.3 (41.7 for the BoNTA group vs. 44.1 for the placebo group, p=.06). There were more women (85.9%) than men (14.1%).
At baseline, the proportion of subjects who had moderate or severe glabellar lines at maximum frown was similar in the BoNTA group (50.6% moderate and 49.4% severe) and the placebo group (47.4% moderate and 52.6% severe) (p>.05) (Table 1).
Table 1. Patient Characteristics and Baseline Glabellar Lines Severity at Maximum Frown
|Variable||Botulinum Toxin Type A (n=170)||Placebo (n=57)||P- Value|
| Age, mean||41.7||44.1||.06|
| Sex, n (%)|
| Male||28 (16.5)||4 (7.0)||.08|
| Female||142 (83.5)||53 (93.0)|| |
| Height, cm, mean||163.6||161.4||.04|
| Weight, kg, mean||59.6||56.8||.07|
| Chinese, n (%)||170 (100.0)||57 (100.0)|| |
|Baseline severity of glabellar lines at maximum frown, n (%)|
| Moderate||86 (50.6)||27 (47.4)||.66|
| Severe||84 (49.4)||30 (52.6)|| |
The percentage of responders peaked at 94.1% (160/170) in the BoNTA group at day 30 and was maintained at 52.9% (90/170) at day 120, compared with 3.5% (2/57) in the placebo group at day 30. The responder rate in the placebo group was 5.3% (3/57) during the study period (Figure 1). At every follow-up visit, the difference in the response rates between the two groups was statistically significant (p<.001).
The investigator's assessment of glabellar line severity at rest was analyzed for the subgroup of subjects with a baseline glabellar line severity score of moderate or severe at rest, which comprised 39 subjects in the BoNTA group and 17 subjects in the placebo group. The proportions of subjects with none or mild scores were higher in the BoNTA group than in the placebo group for all post-injection follow-ups (p<.01). The proportions at days 7, 30, 60, 90, and 120 were 64.1%, 66.7%, 53.85, 48.72, and 33.33, respectively, in the BoNTA group and 5.9%, 0.0%, 0.0%, 5.9%, and 0.0%, respectively, in the placebo group.
In the BoNTA group, the mean scores of subjects' global assessment of change in appearance of glabellar lines were 2.9, 3.1, 2.8, 2.3, and 1.8 at days 7, 30, 60, 90, and 120, respectively. In the placebo group, the mean scores at the same time points were all 0.0. The differences between the mean scores of the two treatment groups were statistically significant at all time points (p<.001). An obvious improvement was found in the BoNTA group. But no improvements were recorded in the placebo group.
The proportion of subjects in the BoNTA group who reported at least 50% improvement in global assessment of glabellar line severity was 95.3% (162/170) at day 30 and decreased to 52.9% (90/170) at day 120. The proportion in the placebo group was 1.7% (1/57) (Figure 2).
Figure 2. Proportion of subjects reporting at least 50% improvement in global assessment of glabellar line severity up to 120 days after botulinum toxin type A treatment.
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In the BoNTA group, the mean changes in self-perception of age at days 7, 30, 60, 90, and 120 were −2.3, −2.8, −2.6, −2.1, and −1.6 years, respectively, showing that treatment made the subjects feel like they looked younger than their chronological ages. In the placebo group, the mean changes at the same time points were −0.1, 0.0, 0.0, 0.0, and 0.0, respectively, showing that no change occurred after treatment. The differences between the two treatment groups were statistically significant for all time points (p<.001).
All participants generally tolerated BoNTA well. Most of the AEs were mild or moderate in severity. SAEs, all of which were considered unrelated to study medication as judged by the investigator, were reported for four subjects treated with BoNTA (1 lumbar vertebral fracture, 1 gastric cancer, 2 breast cancer) and one subject treated with placebo (herpes zoster). Two subjects in the BoNTA group, one with gastric cancer and the other with breast cancer, discontinued the study because of the SAEs. No subject died during the study.
AEs were reported for 55 (32.3%) subjects treated with BoNTA and 11 (19.3%) subjects treated with placebo (p=.06). The most frequently reported AEs (rate>3%) in the BoNTA group were headache (9.4%, 16/170), nasopharyngitis (7.1%, 12/170), and abnormal sensation in the eye (5.3%, 9/170); none were statistically different from the placebo group (p>.05).
The most frequently reported treatment-related AEs were headache (8.8%, 15/170 in the BoNTA treated group; 1.7%, 1/57 in the placebo group, p=.08) and abnormal sensation in the eye (5.3%, 9/170) (Table 2). One subject (0.6%) treated with BoNTA and none (0.0%) of the subjects treated with placebo reported ptosis as an AE. There were no statistically significant differences between the two treatment groups for any laboratory variable or vital sign.
Table 2. Treatment-Related Adverse Events (≥2 subjects)
|Adverse event||Botulinum Toxin Type A (n=170)||Placebo (n=57)||p-Value*|
| Abnormal sensation in the eye||9 (5.3)||0 (0.0%)||.12|
|Diarrhea||2 (1.2)||0 (0.0%)||>/99|
|Administration site pain||2 (1.2)||0 (0.0%)||>/99|
|Abnormal hepatic function||2 (1.2)||0 (0.0%)||>/99|
|Nervous system disorders|
| Headache||15 (8.8)||1 (1.7%)||.08|
| Somnolence||2 (1.2)||0 (0.0%)||>/99|
|Respiratory, thoracic, and mediastinal disorders|
| Influenza||2 (1.2)||0 (0.0%)||>/99|
| Nasopharyngitis||3 (1.8)||0 (0.0%)||.57|
|Skin and subcutaneous tissue disorders|
| Eyelid edema||3 (1.8)||0 (0.0%)||.57|
| Swollen face||3 (1.8)||1 (1.7%)||1|