Reduction of unwanted submental fat with ATX-101 (deoxycholic acid), an adipocytolytic injectable treatment: results from a phase III, randomized, placebo-controlled study

Abstract

Background: Unwanted submental fat (SMF) is aesthetically unappealing, but methods of reduction are either invasive or lack evidence for their use. An injectable approach with ATX-101 (deoxycholic acid) is under investigation.

Objectives: To evaluate the efficacy and safety of ATX-101 for the reduction of unwanted SMF.

Methods: In this double-blind, placebo-controlled, phase III study, 363 patients with moderate/severe SMF were randomized to receive ATX-101 (1 or 2 mg cm(-2) ) or placebo injections into their SMF at up to four treatment sessions ~28 days apart, with a 12-week follow-up. The co-primary efficacy endpoints were the proportions of treatment responders [patients with ≥ 1-point improvement in SMF on the 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS)] and patients satisfied with their face and chin appearance on the Subject Self-Rating Scale (SSRS). Secondary endpoints included skin laxity, calliper measurements and patient-reported outcomes. Adverse events were monitored.

Results: Significantly more ATX-101 recipients met the primary endpoint criteria vs. placebo: on the clinician scale, 59·2% and 65·3% of patients treated with ATX-101 1 and 2 mg cm(-2) , respectively, were treatment responders vs. 23·0% for placebo (CR-SMFRS; P < 0·001); on the patient scale, 53·3% and 66·1%, respectively, vs. 28·7%, were satisfied with their face/chin appearance (SSRS; P < 0·001). Calliper measurements showed a significant reduction in SMF (P < 0·001), skin laxity was not worsened and patients reported improvements in the severity and psychological impact of SMF with ATX-101 vs. placebo. Most adverse events were transient and associated with the treatment area.

Conclusions: ATX-101 was effective and well tolerated for nonsurgical SMF reduction.

Figure 1

Disposition of randomized subjects. Premature treatment discontinuation: patient still completed study follow-up visits. Did not complete study: patient did not complete follow-up visits. AE, adverse event.

Figure 2

Proportion of treatment responders^a at visit 7^b (12 weeks after the final treatment). *OR = 4·73 (95% CI 2·70–8·28); P < 0·001. ^#OR = 6·21 (95% CI 3·52–10·94); P < 0·001. ^a≥ 1-point reduction in submental fat on the 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS); ^blast observation carried forward. Intention-to-treat population. P-values calculated using binary logistic regression. CI, confidence interval; OR, odds ratio.

Figure 3

Proportion of patients satisfied with their appearance in association with their face and chin^a at visit 7^b (12 weeks after the final treatment). *OR = 2·99 (95% CI 1·74–5·14); P < 0·001. ^#OR = 5·22 (95% CI 2·99–9·11); P < 0·001. ^aScore ≥ 4 out of a maximum of 6 on the Subject Self-Rating Scale (SSRS); ^blast observation carried forward. Intention-to-treat population. P-values calculated using binary logistic regression. CI, confidence interval; OR, odds ratio.

Figure 4

Representative images of the aspect of the submental fat of patients before treatment (baseline) and after treatment (12 weeks after the final treatment) with ATX-101 2 mg cm⁻². Note: the patients shown here have provided written, informed consent for their images to be published. CR-SMFRS, Clinician-Reported Submental Fat Rating Scale; SMF, submental fat; SSRS, Subject Self-Rating Scale (satisfaction in association with the appearance of the face and chin).

Figure 5

Change (mean ± SD) in CR-SMFRS from baseline by study visit. *P < 0·001 vs. placebo. Intention-to-treat population. Changes from baseline analysed using an overall analysis of variance (ANOVA). CR-SMFRS, Clinician-Reported Submental Fat Rating Scale.

Figure 6

Change in PR-SMFIS single-item scores (assessing psychological impact of SMF appearance on feelings and perceived visual self-image) from baseline to visit 7 (12 weeks after the final treatment). *P < 0·001. Changes from baseline were analysed by an overall analysis of variance (ANOVA) and pairwise Fisher's Least Significant Difference tests for continuous variables. Intention-to-treat population. PR-SMFIS, Patient-Reported Submental Fat Impact Scale.