An analysis of safety data from five phase III clinical trials on the use of botulinum neurotoxin type A-ABO for the treatment of glabellar lines.

BACKGROUND A new formulation of a botulinum neurotoxin type A (BoNTA-ABO; Dysport [abobotulinumtoxinA]; Medicis Aesthetics, Scottsdale, AZ) was recently approved by the US Food and Drug Administration for the treatment of moderate to severe glabellar lines. OBJECTIVE This article summarizes the safety data from five phase III clinical trials investigating the use of BoNTA-ABO in the treatment of glabellar lines. METHODS Of the five phase III studies conducted, three were multicenter, randomized, placebo-controlled, double-blind studies and two were multicenter, open-label, repeat-dose studies (one of which was an extension trial). Two fixed-dose, placebo-controlled studies randomized a total of 416 patients to receive one 50-unit dose of BoNTA-ABO. The single variable-dose study randomized 544 patients to receive 50 to 80 units of BoNTA-ABO, as determined by gender and patient muscle mass. A substudy of this variable-dose study on QT/QTc prolongation included 50 patients randomized to BoNTA-ABO. One open-label repeat-dose study administered 50 units of BoNTA-ABO to 1200 patients. The single extension study (N = 1415) included both fixed (5423 treatments) and variable dosing (1337 treatments) following a protocol amendment. The extension study included patients from the four previously mentioned studies. Safety endpoints were adverse events (AE), laboratory data, and changes in vital signs. Of 2485 healthy adult patients with moderate to severe glabellar lines enrolled in the trials, 2160 received at least one cycle of BoNTA-ABO. RESULTS Treatment of glabellar lines with 50 units of BoNTA-ABO was well tolerated, with similar rates of treatment-emergent adverse events (TEAE) observed in the active treatment and placebo groups in terms of type, frequency, severity, and relatedness-with the exception of injection site reactions and ptosis. In the variable-dose, single-treatment study, BoNTA-ABO was well tolerated, with an incidence of active TEAE (31%) only slightly greater than that observed for placebo (28%). In the repeat-dose studies, there was no evidence of cumulative safety issues, the incidence of TEAE decreased over time, and patients did not drop out because of TEAE. The most frequently reported AE were nasopharyngitis, sinusitis, upper respiratory tract infection, headache, and injection site reactions. The majority of TEAE were considered unlikely to be related or were not related to BoNTA-ABO treatment. In all studies, the TEAE that were considered possibly related to treatment were primarily headaches (with rates comparable to those observed for placebo), injection site reactions, and eye disorders (such as blepharospasm and eyelid ptosis). There were no clinically significant changes in hematologic or biochemical parameters or in vital signs. The cardiovascular substudy revealed that BoNTA-ABO had no effect on QT/QTc prolongation. CONCLUSIONS Treatment of glabellar lines with BoNTA-ABO is well tolerated. Overall, the safety profile of BoNTA-ABO is comparable to that of placebo in terms of type, frequency, severity, and relatedness of AE.