The percentage of subjects rating themselves as improved or better on the GAIS was 95% or greater across all dose groups at days 30 and 60 (Figure 5). Over time, the percentage of subjects in the higher dose groups who rated themselves as improved or better was greater than that of the lower dose groups with a clear dose-response relationship evident at day 180. Subjects treated with 50, 75, and 100U INCO are shown at baseline, days 30, 180, and 240, and at visit when return to baseline was observed in Figure 6.
Primary Safety Endpoints
The incidence of TEAEs over the main period was 23 (37.1%) for the 20U group (N=62), 23 (38.3%) for the 50U group (N=60), 26 (42.6%) for the 75U group (N=61), and 22 (37.9%) for the 100U group (N=58) (Table 3). The TEAEs with incidences rate ≥ 5% were nasopharyngitis (14.5%) and headache (7.1%). Only one serious TEAE was reported (an appendicitis in the 100U group that the investigator determined was not related to treatment). No new or unexpected adverse events were observed.
The incidence of treatment-related adverse events was low across all doses (20U:7[11.3%], 50U:6[10.0%], 75U:8[13.1%], and 100U:7[12.1%]) (Table 3). All treatment-related TEAEs were mild to moderate in intensity. No treatment related serious TEAEs were reported. Only five subjects (2.1%) reported TEAESIs: eyelid ptosis (4[1.7%], all related to treatment with duration ranging from 44–108 days); and constipation (1[0.4%], unrelated to treatment).
DISCUSSION
These results demonstrate a clear INCO dose effect of at least
6 months duration for the majority of GFL subjects as assessed
by ≥1-point improvement from baseline severity at maximum
frown on the FWS. There was a consistent prolongation in the
median duration of effect with increasing doses. For the primary
endpoint, effect was observed in all dose groups up to day 90
and a strong dose effect became apparent thereafter. From day
120 there was a clear differentiation in duration between 20U,
50U and the two higher dose groups. After day 180, the best
