Open-Label Study of Deoxycholic Acid for the Reduction of Localized Subcutaneous Fat in the Submental Area

Multicenter, Open-label Study of ATX-101 (Sodium Deoxycholate Injection) for the Reduction of Localized Subcutaneous Fat in the Submental Area

To evaluate the safety of deoxycholic acid subcutaneous injections in the submental area (below the chin).

Study Overview

• Status: Completed
• Conditions: Moderate or Severe Submental Fullness
• Intervention / Treatment: Drug: Deoxycholic acid injection

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90212
      • Mark Rubin
    • LaJolla, California, United States, 92121
      • Mitchel Goldman
    • San Juan Capistrano, California, United States, 92675
      • Jeffrey Klein
    • Santa Monica, California, United States, 90404
      • Steven Teitelbaum
    • Santa Monica, California, United States, 90404
      • Ava Shamban
  • Florida
    • Bradenton, Florida, United States, 34209
      • Susan Weinkle
    • West Palm Beach, Florida, United States, 33401
      • Palm Beach Cosmetic
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Steven Dayan
  • Louisiana
    • New Orleans, Louisiana, United States, 70124
      • Lupo Center for Aesthetic and General Dermatology
  • Michigan
    • Warren, Michigan, United States, 48088
      • Grekin Skin Institute
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • David Goldberg, MD
  • New York
    • New York, New York, United States, 10016
      • Roy Geronemus, MD
    • New York, New York, United States, 10028
      • Macrene Alexiades-Armenakas
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • Sue Ellen Cox
  • Pennsylvania
    • Yardley, Pennsylvania, United States, 19067
      • Richard Fried
  • Tennessee
    • Nashville, Tennessee, United States, 37215
      • Michael Gold
  • Texas
    • Houston, Texas, United States, 77056
      • Suzanne Bruce
    • Plano, Texas, United States, 75093
      • Jeffrey Adelglass

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Submental fat graded by the investigator as 2, 3, or 4 using the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and graded by the subject as 2, 3, or 4 using the Patient-Reported Submental Fat Rating Scale (PR-SMFRS) as determined on visit 1 (within 28 days before the subject's first dosing session)
• Dissatisfaction with the submental area rated by the subject as 0, 1, or 2 using the Subject Self-rating Scale (SSRS) as determined on visit 1 (within 28 days before the subject's first dosing session)
• Males and nonpregnant, nonlactating females 18 years of age or greater, on the day of the subject's first dosing session (visit 2). Females of childbearing potential must have a negative human chorionic gonadotropin (serum) test result within 28 days before visit 2 and agree to practice adequate contraception, in the judgment of the investigator, during the course of the study
• A normal result on coagulation tests (prothrombin time (PT), partial thromboplastin time (PTT)) obtained within 28 days before subject's first dosing session
• History of stable body weight, in the judgment of the investigator, for at least 6 months before subject's first dosing session
• Expected to understand and comply with the visit schedule and all protocol-specified tests and procedures and agreement by the subject to refrain from making significant changes, in the judgment of the investigator, to his or her dietary or exercise habits during the course of the subject's participation
• Medically able to undergo the administration of study drug determined by clinical and laboratory tests obtained within 28 days before subject's first dosing session for which the investigator identifies no clinically significant abnormality
• Signed informed consent obtained before any study-specific procedure is performed

Exclusion Criteria:

• History of any intervention to treat submental fat (eg, liposuction, surgery, or lipolytic agents)
• History of trauma associated with the chin or neck areas, which in the judgment of the investigator may affect evaluation of safety or efficacy of treatment
• A grade of 4 on the Submental Skin Laxity Grading scale (SMSLG) or any other anatomical feature (eg, predominant subplatysmal fat, loose skin in the neck or chin area, prominent platysmal bands) for which reduction in submental fat may, in the judgment of the investigator, result in an aesthetically unacceptable outcome
• Evidence of any cause of enlargement in the submental area (eg, thyroid enlargement, cervical adenopathy) other than localized submental fat
• Body mass index of ≥ 40 kg/m² as determined on visit 1 (week 0)
• History or current symptoms of dysphagia
• Any medical condition that would interfere with assessment of safety or efficacy or compromise the subject's ability to undergo study procedures or give informed consent
• Treatment with radio frequency, laser procedures, chemical peels, or dermal fillers in the neck or chin area within 12 months before the first treatment session, or botulinum toxin injections in the neck or chin area within 6 months before the first treatment session
• History of sensitivity to any components of the study drug or to topical or local anesthetics (eg, lidocaine, benzocaine, novocaine)
• Previous treatment in this study or previous participation in a Kythera-sponsored ATX-101 study
• Treatment with an investigational device or agent within 30 days before the subject's first treatment session

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Deoxycholic Acid 2 mg/cm²; Participants received deoxycholic acid 2 mg/cm² administered in 0.2 mL injections, up to 10 mL per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.	Drug: Deoxycholic acid injection; Formulated as an injectable solution containing deoxycholic acid at a concentration of 10 mg/mL.; Other Names: Kybella; ATX-101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	Serious AEs include any event that met one or more of the following criteria: was fatal or life-threatening, required inpatient hospitalization or prolonged a hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or a significant medical hazard. The severity of each AE was defined as either: Mild: The participant was aware of the sign or symptom, but it was easily tolerated. Moderate: The sign or symptom caused discomfort and interfered with usual activity. Severe: The sign or symptom was incapacitating, and the participant was unable to engage in usual activity. The investigator determined the relationship of each AE to the study drug using the question: "Is there a reasonable possibility that the event may have been caused by treatment with the study drug?"	Up to 12 months after last treatment (maximum of 18 months from first treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Clinician-Reported Submental Fat Rating Scale Scores (CR-SMFRS)	The CR-SMFRS score is based on the investigator's clinical evaluation of the participant, where submental fullness is scored on a 5-point ordinal scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = extreme). A negative change from baseline indicates improvement.	Baseline and months 3, 6, 9, and 12 after last treatment
Mean Change From Baseline in Patient-Reported Submental Fat Scale Rating Scale (PR-SMFRS)	The PR-SMFRS is based on the participant's response to the question "How much fat do you have under your chin right now?" and answered on a 5-point ordinal scale (0 = no chin fat at all, 1 = a slight amount of chin fat, 2 = a moderate amount of chin fat, 3 = a large amount of chin fat, and 4 = a very large amount of chin fat). A negative change from baseline indicates improvement.	Baseline and month 3 and month 12 after last treatment
Percentage of Participants Who Achieved a Composite 1-grade Response	A composite 1-grade response is defined as at least a 1-grade improvement from baseline on both the CR-SMFRS and PR-SMFRS. The CR-SMFRS score is based on the investigator's clinical evaluation of the participant, where submental fullness is scored on a 5-point ordinal scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = extreme). The PR-SMFRS is based on the participant's response to the question "How much fat do you have under your chin right now?" and answered on a 5-point ordinal scale (0 = no chin fat at all, 1 = a slight amount of chin fat, 2 = a moderate amount of chin fat, 3 = a large amount of chin fat, and 4 = a very large amount of chin fat).	Baseline and month 3 and month 12 after last treatment
Percentage of Participants Who Achieved a Composite 2-grade Response	A composite 2-grade response is defined as at least a 2-grade improvement from baseline on both the CR-SMFRS and PR-SMFRS. The CR-SMFRS score is based on the investigator's clinical evaluation of the participant, where submental fullness is scored on a 5-point ordinal scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = extreme). The PR-SMFRS is based on the participant's response to the question "How much fat do you have under your chin right now?" and answered on a 5-point ordinal scale (0 = no chin fat at all, 1 = a slight amount of chin fat, 2 = a moderate amount of chin fat, 3 = a large amount of chin fat, and 4 = a very large amount of chin fat).	Baseline and month 3 and month 12 after last treatment
Mean Change From Baseline in Patient-Reported Submental Fat Impact Scale (PR-SMFIS)	The PR-SMFIS assesses the impact of submental fat on self-perception of 6 emotional and visual characteristics (unhappy, bothered, self-conscious, embarrassed, look older, and look overweight) related to the appearance of submental fullness as evaluated by the participant. Each item is rated on an 11-point numeric scale from 0 to 10. Scores for the 6 items were averaged to generate a PR-SMFIS total scale score ranging from 0 to 10 where 0 is a positive outcome and 10 is a negative outcome. A negative change from baseline indicates improvement.	Baseline and month 3 and month 12 after last treatment
Mean Change From Baseline in Subject Self Rating Scale (SSRS)	The SSRS assesses participants' satisfaction with their appearance in association with the face and chin on a 7-point scale from 0 to 6 (0 = extremely dissatisfied, 1 = dissatisfied, 2 = slightly dissatisfied, 3 = neither satisfied nor dissatisfied, 4 = slightly satisfied, 5 = satisfied and 6 = extremely satisfied). A positive change from baseline indicates improvement.	Baseline and month 3 and month 12 after last treatment
Mean Change From Baseline in Self-rating of Attractiveness	Self-rating of Attractiveness assesses aspects of appearance from the participant's perspective with a series of 6 questions: How attractive do you think your overall appearance (chin/neck, eyes, nose, mouth, entire face) is/are?" Each question was answered on a scale from 1 to 9 (1 = not at all attractive, 5 = neither attractive nor unattractive, and 9 = extremely attractive). A positive change from baseline indicates improvement.	Baseline and month 3 and month 12 after last treatment
Response to Subject Global Questions	Participants answered 3 questions on a 7-point scale that ranged from "a great deal worse" to "a great deal better" (questions 1 and 2) or from "extremely dissatisfied" to "extremely satisfied" (question 3). Question 1: Since the start of the study, how would you rate the fat under your chin right now? Question 2: Since the start of the study, how would you rate the definition between your chin and neck right now? Question 3: How satisfied are you with the treatment you received in this study?	Month 3 and month 12 after last treatment
Percent Change From Baseline in Submental Fat Thickness	Submental fat thickness was measured using calipers.	Baseline and month 3 and month 12 after last treatment
Change From Baseline in Submental Skin Laxity Grade (SMSLG)	SMSLG assessment was based on clinical evaluation and palpation of the submental area. The SMSLG scale incorporates 3 features: skin wrinkling, adherence to underlying neck structures (bone and muscle) and redundancy (horizontal and vertical folds). Grade 1 (none): no or minimal superficial wrinkling, skin well apposed to deeper neck structures, no skin redundancy (no skin draping (vertical folds) or skin sagging (horizontal folds)); Grade 2 (mild): mild superficial wrinkling, skin well apposed to deeper neck structures, minimal skin redundancy (slight skin draping and sagging); Grade 3 (moderate): may have mild to moderate superficial wrinkling, skin has mild to moderate separation from deeper neck structures, moderate skin redundancy (moderate skin draping and skin sagging); Grade 4 (severe): mild to marked superficial wrinkling, loose skin separated from deeper neck structures, marked skin redundancy (marked skin draping and sagging).	Baseline and month 3 and month 12 after last treatment
Change From Baseline in Line Drawing Assessment	Each participant was given 2 example line drawings representing each of the 5 submental fat grades (0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = extreme) and asked to select the drawing that best represents their current profile. Improvement is any decrease in grade, and worsening is any increase in grade.	Baseline and month 3 after last treatment

Collaborators and Investigators

• Sponsor: Kythera Biopharmaceuticals
• Investigators: Study Director: Frederick Beddingfield, III, M.D., PhD, Kythera Biopharmaceuticals, Inc

Publications and helpful links

General Publications

• Beer K, Weinkle SH, Cox SE, Rubin MG, Shamban A, Somogyif C. ATX-101 (Deoxycholic Acid Injection) for Reduction of Submental Fat: Results From a 12-Month Open-Label Study. J Drugs Dermatol. 2019 Sep 1;18(9):870-877.

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (ACTUAL): June 1, 2013
• Study Completion (ACTUAL): June 1, 2013

Study Registration Dates

• First Submitted: August 26, 2011
• First Submitted That Met QC Criteria: August 30, 2011
• First Posted (ESTIMATE): August 31, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): January 14, 2016
• Last Update Submitted That Met QC Criteria: December 8, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Gastrointestinal Agents; Cholagogues and Choleretics; Deoxycholic Acid
• Other Study ID Numbers: ATX-101-11-26