A double-blind, randomized, placebo-controlled, two-dose comparative study of botulinum toxin type A for treating glabellar lines in Japanese subjects

Abstract

Background: Systematic, well-controlled clinical trials of botulinum toxin type A (BoNTA) in diverse patient populations are needed. The aim of this study was to characterize the safety and efficacy of 10-U and 20-U BoNTA doses versus placebo for treating glabellar lines in Japanese subjects.

Methods: A 16-week, multicenter, double-blind, randomized, placebo-controlled trial comparing 10 or 20 U of BoNTA versus placebo in 142 Japanese subjects with glabellar lines of at least moderate severity at maximal contraction. The primary efficacy endpoint was physician-rated line severity at maximal contraction 4 weeks after treatment. Secondary efficacy endpoints included physician/subject ratings and estimates of the effect's duration.

Results: Response rates by physician-rated line severity at maximal contraction (week 4) were 86.4% (10 U), 88.6% (20 U), and 0% (placebo, p < 0.001). Line severity at maximal contraction in each BoNTA group (p < 0.001) improved significantly from baseline at each visit. BoNTA and placebo differed significantly on all other efficacy measures. Mean duration of effect was 9.4 weeks in the 20-U group and 7.9 weeks in the 10-U BoNTA group. No serious adverse events occurred.

Conclusion: Doses of BoNTA of 10 and 20 U are effective and safe for treating glabellar lines in Japanese subjects, and the 20-U dose provides greater efficacy and longer duration of effect.

Fig. 1

Study design and patient flow through study

Fig. 2

Percentage of responders (line severity = none or mild) at maximal contraction (physician ratings). *p < 0.001, 10 U vs. placebo and 20 U vs. placebo; 10 U vs. 20 U not significant. Calculated in the full analysis set

Fig. 3

Mean change from baseline in line severity at maximal contraction (physician ratings). *p < 0.001, 10 U vs. placebo and 20 U vs. placebo; 10 U vs. 20 U not significant

Fig. 4

Subgroup analysis: percentage of responders among subjects with pretreatment line severity at rest of ≥2 (lines are noticeable or readily apparent; physician ratings). 10 U vs. placebo, all visits, p ≤ 0.019; 20 U vs. placebo, all visits, p < 0.001. *10 U vs. 20 U, week 8, p = 0.037; all other visits, not significant. Calculated in the full analysis set

Fig. 5

Subject assessment of line improvement: Percentage of responders. All comparisons between 10 U vs. placebo and 20 U vs. placebo, p < 0.001; *10 U vs. 20 U, p = 0.035 at week 8; all other visits are not significant. Calculated in the full analysis set

Fig. 6

Subject satisfaction ratings (scores of 1, 2, 3). All comparisons between 10 U vs. placebo and 20 U vs. placebo, p < 0.001; no significant differences between 10 U and 20 U. Calculated in the full analysis set

Fig. 7

Duration of effect of BoNTA: Kaplan–Meier curve of treated subjects with scores of 0 (none) or 1 (mild)