Study Design and Intervention
GROUP B
This was a phase 3, multicenter, randomized study comprising a double-blind phase followed by an open-label phase (ClinicalTrials.gov, NCT02450526), conducted at ten centers in China between April 2015 and September 2017. Since the volumes to be administered per injection site differed for aboBoNT-A and the active comparator onaBoNT-A, two separate matching placebos (i.e., one each for aboBoNT-A and onaBoNT-A) were used to maintain the blinding status at the product level. Hence, patients were randomized into four treatment groups to receive 1 cycle of aboBoNT-A (Group A), matching aboBoNT-A placebo (Group B), active comparator (onaBoNT-A; Group C), or matching comparator placebo (Group D). Patients were randomized to receive aboBoNT-A or comparator in a 3:1 ratio. Within the aboBoNT-A group, patients received either the treatment or placebo in a 5:1 ratio (Group A: Group B). Patients within the comparator group also received active treatment or placebo in a 5:1 ratio (Group C: Group D). Randomization was stratified by sex and baseline severity of glabellar lines at maximum frown, measured by investigator’s live assessment (ILA), to minimize bias in treatment allocation within the specified levels of these factors, thus avoiding confounding the treatment effect. Randomization was performed by an independent statistician in blocks based on computer-generated randomization lists and was managed using an interactive web response system.Study treatments were administered in five predefined sites across the glabellar area: two injections into both corrugator muscles and one into the procerus muscle near the nasofrontal angle. Patients received aboBoNT-A 50 U (10 U [0.05 mL] per injection site), onaBoNT-A 20 U (4 U [0.1 mL] per injection site), matching aboBoNT-A placebo (containing the excipients from aboBoNT-A reconstituted with 1.5 mL of sodium chloride solution), or matching onaBoNT-A placebo (1.5 mL of sodium chloride solution). After treatment, all patients attended follow-up visits on days 8, 29, 57, and 85. After the double-blind treatment cycle (cycle 1), patients received a maximum of four additional cycles (cycles 2−5) with open-label aboBoNT-A 50 U at intervals of  ≥ 84 days (12 weeks) between each cycle, depending on individual patient duration of response to treatment. Patients could start the next treatment cycle (retreatment) if their glabellar line severity had returned to moderate or severe, regardless of the severity of their glabellar lines at baseline. Patients who were ineligible for retreatment were evaluated every 28 days at additional follow-up visits in each treatment cycle until they were eligible for retreatment. Patients completed the study when they had attended the day 85 visit after their fifth injection (including cycle 1), or when they had been in the whole study for 15 months.