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

Study Overview
=================
Brief Summary
-----------------
To evaluate the safety of deoxycholic acid subcutaneous injections in the submental area (below the chin).

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

Conditions
-----------------
Moderate or Severe Submental Fullness

Intervention / Treatment
-----------------
* Drug: Deoxycholic acid injection


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deoxycholic Acid 2 mg/cm²<br>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<br>* Formulated as an injectable solution containing deoxycholic acid at a concentration of 10 mg/mL.<br>* Other names: Kybella;|

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 |