Efficacy, patient-reported outcomes and safety profile of ATX-101 (deoxycholic acid), an injectable drug for the reduction of unwanted submental fat: results from a phase III, randomized, placebo-controlled study

Abstract

Background: Unwanted submental fat (SMF) may result in an unattractive chin profile and dissatisfaction with appearance. An approved and rigorously tested non-surgical method for SMF reduction is lacking.

Objective: To evaluate the efficacy and safety of ATX-101 for the pharmacological reduction of unwanted SMF in a phase III randomized, double-blind, placebo-controlled study.

Methods: Patients (n = 360) with moderate or severe SMF were randomized to receive ATX-101 1 or 2 mg/cm(2) or placebo injected into their SMF for up to four treatments ~28 days apart, with a 12-week follow-up. Coprimary efficacy endpoints were the proportions of treatment responders, defined as a ≥1-point reduction in SMF on the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS), and those satisfied with their appearance in association with their face and chin after treatment on the Subject Self-Rating Scale (SSRS score ≥4). Secondary efficacy endpoints included a ≥1-point improvement in SMF on the Patient-Reported Submental Fat Rating Scale (PR-SMFRS) and changes in the Patient-Reported Submental Fat Impact Scale (PR-SMFIS). Additional patient-reported outcomes and changes in the Skin Laxity Rating Scale were recorded. Adverse events (AEs) and laboratory test results were monitored.

Results: Compared with placebo, a greater proportion of patients treated with ATX-101 1 and 2 mg/cm(2) showed a ≥1-point improvement in CR-SMFRS (58.3% and 62.3%, respectively, vs. 34.5% with placebo; P < 0.001) and patient satisfaction (SSRS score ≥4) with the appearance of their face and chin (68.3% and 64.8%, respectively, vs. 29.3%; P < 0.001). Patient-reported secondary efficacy endpoints showed significant improvements in SMF severity (PR-SMFRS; P = 0.009 for ATX-101 1 mg/cm(2) , P < 0.001 for ATX-101 2 mg/cm(2) vs. placebo) and emotions and perceived self-image (PR-SMFIS; P < 0.001). No overall worsening of skin laxity was observed. AEs were mostly transient, mild to moderate in intensity and localized to the treatment area.

Conclusion: ATX-101 was effective and well tolerated, and may be an alternative to surgery for patients desiring improvement of their submental profile.

Figure 1

Schematic disposition of randomized patients into different treatment groups. AE, adverse event.

Figure 2

Proportion of responders* to treatment at Visit 7^† (12 weeks after the final treatment). Intention-to-treat population. *≥1-point reduction in submental fat on the Clinician-Reported Submental Fat Rating Scale; ^†last observation carried forward; ^‡OR = 2.60 (95% CI 1.52–4.43), binary logistic regression (P < 0.001, Bonferroni–Holm testing procedure); ^§OR = 3.13 (95% CI 1.83–5.36), binary logistic regression (P < 0.001, Bonferroni–Holm testing procedure). CI, confidence interval; OR, odds ratio.

Figure 3

Proportion of patients satisfied with the appearance of their face and chin* at Visit 7^† (12 weeks after the final treatment). Intention-to-treat population. *Score ≥4 of a maximum of 6 on the Subject Self-Rating Scale; ^†last observation carried forward; ^‡OR = 5.37 (95% CI 3.06–9.44), binary logistic regression (P < 0.001, Bonferroni–Holm testing procedure); ^§OR = 4.62 (95% CI 2.65–8.04), binary logistic regression (P < 0.001, Bonferroni–Holm testing procedure). CI, confidence interval; OR, odds ratio.

Figure 4

Representative images of the aspect of the SMF of patients before (at baseline) and after treatment (Visit 7) with ATX-101 2 mg/cm² (a, b) and 1 mg/cm² (c, d). CR-SMFRS, Clinician-Reported SMF Rating Scale; SSRS, Subject Self-Rating Scale; SMF, submental fat.

Figure 5

Proportion of patients with an improvement in Patient-Reported Submental Fat Rating Scale (PR-SMFRS) score from baseline to Visit 7 (12 weeks after the final treatment). Intention-to-treat population. *P = 0.009; ^†P < 0.001 relative to placebo (Pearson's chi-square test).

Figure 6

Change in patient evaluations of the psychological impact of their submental fat (Patient-Reported Submental Fat Impact Scale [PR-SMFIS] component scores) from baseline to Visit 7 (12 weeks after the final treatment). Intention-to-treat population. *P < 0.001 relative to placebo (analysis of variance and post hoc Fisher's least significant difference tests).

Figure 7

Treatment-emergent adverse events at the injection site (incidence ≥10%). Percentages are based on the number of patients in the safety population.