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(Deoxycholic Acid Injection) for Reduction of Submental Fat: Results from a 12-Month Open-Label Study Kenneth Beer MD,ª Susan H

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(Deoxycholic Acid Injection) for Reduction of Submental Fat: Results from a 12-Month Open-Label Study Kenneth Beer MD,ª Susan H To order reprints or e-prints of JDD articles please contact [email protected] September 2019 870 Volume 18 • Issue 9 Copyright © 2019 ORIGINAL ARTICLE Journal of Drugs in Dermatology SPECIAL TOPIC ATX-101 (Deoxycholic Acid Injection) for Reduction of Submental Fat: Results From a 12-Month Open-Label Study Kenneth Beer MD,ª Susan H. Weinkle MD,b Sue Ellen Cox MD,c Mark G. Rubin MD,d Ava Shamban MD,e and Christine Somogyif ªBeer Surgical, Aesthetic and General Dermatology, West Palm Beach, FL bUniversity of South Florida, Tampa and Private Practice, Bradenton, FL cDepartment of Dermatology, University of North Carolina School of Medicine and Aesthetic Solutions, Chapel Hill, NC dLasky Skin Center, Beverly Hills, CA ePrivate Practice, Santa Monica, CA fAllergan plc, Irvine, CA ABSTRACT Background: ATX-101 (deoxycholic acid) causes adipocytolysis when injected into subcutaneous fat. Objective: Evaluate the long-term safety and efficacy of ATX-101 for submental fat (SMF) reduction. Methods: Adults (N=165) with moderate-to-extreme SMF received ≤6 treatments of open-label ATX-101 (2 mg/cm2) and were evalu- ated up to 12 months after last treatment. Efficacy end points included improvements in SMF based on clinician or subject assessment, patient-reported outcomes, downtime (via subject questionnaire), and skin laxity. Safety was evaluated throughout the study. Results: Twelve weeks after last treatment, most subjects achieved a ≥1-grade improvement in SMF based on clinician (86.8%) or sub- ject (83.8%) evaluation; at 12 months, 90.4% and 80.7% of these responders, respectively, maintained the response. Overall, 84.9% of subjects were satisfied with the appearance of their face/chin. At 12 months, 82.9% of subjects had unchanged, and 10.1% had improved, skin laxity relative to 12 weeks after last treatment. Adverse events were mild to moderate and mainly involved the treatment area. During the 7 days after the first treatment, 13.3% of subjects missed work and 33.9% missed social/leisure activities. Following subsequent treatments, 2.4%–6.0% of subjects missed work and 10.0%–15.7% missed social/leisure activities. Conclusion: The safety and efficacy of ATX-101 were sustained over 12 months. ClinicalTrials.gov identifer, NCT01426373 Do Not Copy J Drugs Dermatol. 2019;18(9):870-877. Penalties Apply INTRODUCTION into fat, ATX-101 causes adipocytolysis and a local tissue re- he submental area impacts facial harmony, balance, sponse involving macrophage infltration to eliminate cellular and attractiveness.1-3 In addition, an undesirable sub- debris and liberated lipids from the injection site, as well as mental profle can negatively affect self-perception.4,5 fbroblast recruitment thought to be responsible for neocolla- T 17-19 Accumulation of submental fat (SMF) can occur in individuals genesis. not otherwise overweight and is typically resistant to weight reduction measures.6-8 The safety and effcacy of ATX-101 have been assessed in 4 large randomized, controlled phase 3 trials.14,15,20-23 The current Treatment options to improve submental contour have tradi- trial evaluated the safety and durability of the ATX-101 treat- tionally included surgical procedures.9 Nonsurgical methods of ment effect over 12 months. The impact of ATX-101 treatment submental contouring are available, although many tighten skin on work and social/leisure activities was also assessed. rather than reduce SMF.10-13 ATX-101 (deoxycholic acid injection) is an injectable drug approved in the United States (Kybella)14 METHODS and Australia, Canada, Europe, and South Korea (Belkyra)15 for Study Design improvement in the appearance of moderate-to-severe convex- This open-label, phase 3b trial (ClinicalTrials.gov identifer, ity or fullness associated with SMF. NCT01426373) was conducted between August 2011 and June 2013 at 18 sites in the United States in compliance with the In- The active ingredient of ATX-101, deoxycholic acid, preferen- ternational Conference on Harmonization Guideline for Good tially targets adipocytes, as the cytolytic activity is diminished Clinical Practice and the Declaration of Helsinki. All participants in protein-rich tissues such as muscle and skin.16 When injected provided written informed consent. This document contains proprietary information, images and marks of Journal of Drugs in Dermatology (JDD). No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD. JO0919 If you feel you have obtained this copy illegally, please contact JDD immediately at [email protected] To order reprints or e-prints of JDD articles please contact [email protected] 871 Journal of Drugs in Dermatology K. Beer, S.H. Weinkle, S.E. Cox, et al September 2019 • Volume 18 • Issue 9 All subjects received open-label ATX-101 (area-adjusted dose: line as evaluated by the clinician using the CR-SMFRS (wherein 2 mg/cm2) by subcutaneous injection into preplatysmal SMF. clinicians rate SMF on a 5-point scale ranging from absent [0] to Consistent with the product label,14,15 up to 10 mL of ATX-101 extreme [4]) and by the subject using the PR-SMFRS (wherein could be injected per treatment, and subjects were eligible to subjects rate their chin fat on a 5-point scale ranging from none receive up to 6 treatments (every 28±5 days). Subjects could re- [0] to very large amount [4]). The psychological impact of SMF ceive <6 treatments due to insuffcient SMF to safely inject study was assessed by the subject via the validated Patient-Reported drug, subject satisfaction with treatment, or safety/tolerability SMF Impact Scale (PR-SMFIS), which includes 6 questions, each concerns. Subjects were evaluated at Weeks 0, 4, 8, 12, 16, and rated on a scale from 0 (no impact) to 10 (greatest negative im- 20 and at approximately 7 days after each treatment during the pact).24 Subject satisfaction with the appearance of their face/ open-label period. During the follow-up period, subjects were chin was assessed via the 7-point SSRS, while self-ratings of evaluated at 4 weeks; 12 weeks (primary time point in phase attractiveness were assessed via the Self-Ratings of Attractive- 3 trials); and 6, 9, and 12 months after last treatment. Subjects ness questions in which subjects rated their features on a scale who did not complete the 12-month visit were considered to of 1 to 9, with higher numbers indicating greater attractiveness. have discontinued from the study. The SMSLG scale (ranging from none [1] to severe [4]) was used by the clinician to evaluate skin laxity. Detailed descriptions of Subjects these scales have been previously published.14,21 SMF thickness Adults (≥18 years) who had at least moderate SMF (grade 2, 3, or was measured using calipers. A questionnaire completed by the 4 on both the validated Clinician-Reported and Patient-Reported subject assessed the effect of ATX-101 treatment on work and SMF Rating Scale [CR-SMFRS and PR-SMFRS, respectively]) social/leisure activities. At select sites, standardized photogra- and were dissatisfed with the appearance of their face/chin phy was performed at baseline, 12 weeks after last treatment, (score of 0, 1, or 2 on the Subject Self-Rating Scale [SSRS]) were and 12 months after last treatment. eligible. In addition, body weight had to be stable for ≥6 months. Exclusion criteria included body mass index (BMI) >40 kg/m2; Statistical Analysis prior treatment of SMF (liposuction, surgery, lipolytic agents); Safety data are reported for the safety population (subjects who treatment in the chin/neck within 6 months (botulinum toxin) or received ≥1 injection of ATX-101). AEs were summarized by se- 12 months (radiofrequency, lasers, chemical peels, dermal fll- verity, association with treatment area, study drug relatedness, ers); prior trauma to chin/neck that may affect safety/effcacy and those leading to discontinuation of treatment or death. Eff- evaluations; enlargement of the submental area for any reason cacy evaluations were based on the treatment effect population other than SMF; history or current symptoms of dysphagia;Do anyNot (subjectsCopy who received ≥1 injection of ATX-101 and who had any medical condition that would compromise the subject’sPenalties ability post-treatment Apply data for effcacy or skin laxity). to undergo study procedures or interfere with study assess- ments; or excessive skin laxity (grade 4 on the Submental Skin Categories of observed scores and change from baseline were Laxity Grade [SMSLG] scale) or other anatomical feature (loose summarized for each visit using frequency counts and percent- skin in the chin/neck, prominent platysmal bands) for which SMF ages. Descriptive statistics were provided for numerical values. reduction may result in an aesthetically unacceptable outcome. Responder analyses were categorized as subjects who achieved a ≥1-grade improvement in SMF from baseline on the CR- Assessments SMFRS (CR-1 response), PR-SMFRS (PR-1 response), and both The primary objective was to assess the safety of ATX-101 treat- CR-SMFRS and PR-SMFRS (composite CR-1/PR-1 response). ment as evaluated by the incidence and severity of adverse events (AEs) as well as changes in vital signs and clinical labora- RESULTS tory test results. At each visit (before ATX-101 administration), Subject Disposition and Demographics the treatment area was examined by the clinician, and each sub- Of the 255 subjects screened, 165 were enrolled and included in ject was interviewed in an open-ended manner to inquire about the safety and treatment effect populations (Figure 1). Most sub- any AEs since the previous visit. In addition to evaluation of jects (82.4%) completed the open-label period; 79.4% completed spontaneously reported AEs, a checklist of commonly reported the study (including 12 months of follow-up). Of the subjects AEs was used as a guide for the clinician evaluating the sub- who discontinued prior to study completion, 6 withdrew due to ject.
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