Evaluation of Safety and Efficacy of Deoxycholic Acid Injection (ATX-101) in the Reduction of Submental Fat

• Deoxycholic acid injection (Drug), also known as ATX-101
• Placebo (Drug): Phosphate buffered saline placebo for injection

Primary outcomes

• Percentage of Participants With a Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) 1-grade Response [Baseline and 12 weeks after last treatment (up to 24 weeks after first dose)]: A CR-SMFRS response is defined as at least a 1-point improvement (i.e. 1-point reduction) from Baseline 12 weeks after the last treatment. 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 (0-4) with 0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = extreme.
• Percentage of Participants With a Subject Self Rating Scale (SSRS) Response [Baseline and 12 weeks after last treatment (up to 24 weeks after first dose)]: A SSRS response is defined as an SSRS score that is 4 or greater 12 weeks after the last treatment. The SSRS assesses participant's satisfaction with their appearance in association with the face and chin on a 7-point scale from 0 to 6: where 0 = Extremely dissatisfied, 1 = Dissatisfied, 2 = Slightly dissatisfied, 3 = Neither satisfied nor dissatisfied, 4 = Slightly satisfied, 5 = Satisfied and 6 = Extremely satisfied.

Secondary outcomes

• Percentage of Participants With a CR-SMFRS 2-grade Response [Baseline and 12 weeks after last treatment (up to 24 weeks after first dose)]: A CR-SMFRS 2-grade response is defined as at least a 2-point improvement (i.e. 2-point reduction) from Baseline 12 weeks after the last treatment. 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 (0-4) with 0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = extreme.
• Change From Baseline in CR-SMFRS Score [Baseline and 12 weeks after last treatment (up to 24 weeks after first dose)]: 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 (0-4) with 0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = extreme. A negative change from Baseline indicates improvement.
• Change From Baseline in SSRS Scores [Baseline and 12 weeks after last treatment (up to 24 weeks after first dose)]: The SSRS assesses participant's satisfaction with their appearance in association with the face and chin on a 7-point scale from 0 to 6: where 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.
• Change From Baseline in Submental Fat Thickness [Baseline and 12 weeks after last treatment (up to 24 weeks after first dose)]: Submental thickness was measured using caliper devices.
• Change From Baseline in Patient-reported Submental Fat Rating Scale (PR-SMFRS) [Baseline and 12 weeks after last treatment (up to 24 weeks after first dose)]: The PR-SMFRS is based on the participant's response to the question "How much fat do you currently have under your chin?" answered on a 5-point ordinal scale (0-4) with 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. Improvement is defined as any decrease in score and worsened as any increase in score.
• Change From Baseline in Patient-Reported Submental Fat Impact Scale (PR-SMFIS) [Baseline and 12 weeks after last treatment (up to 24 weeks after first dose)]: The PR-SMFIS assesses the impact of submental fat on self-perception of 6 characteristics 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.
• Change From Baseline in Self-rating of Attractiveness [Baseline and 12 weeks after last treatment (up to 24 weeks after first dose)]: Self-rating of attractiveness assesses aspects of appearance from the participant's perspective by 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 where 1 = Not at all attractive, 5 = Neither attractive nor unattractive and 9 = Extremely attractive. A positive change from Baseline indicates improvement.
• Change From Baseline in Derriford Appearance Scale 24 (DAS24) [Baseline and 12 weeks after last treatment (up to 24 weeks after first dose)]
• Change From Baseline in Body Image Quality of Life Inventory (BIQLI) [Baseline and 12 weeks after last treatment (up to 24 weeks after first dose)]

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

Inclusion Criteria:

1. Submental fat graded by the investigator as 2 or 3 using the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) as determined on Visit 2.
2. Dissatisfaction with the submental area rated by the subject as 0, 1, 2, or 3 using the Subject Self Rating Scale (SSRS).
3. Males and nonpregnant, nonlactating females between 18 and 65 years of age, inclusive on the day of randomization. Females of childbearing potential must have a negative human chorionic gonadotropin (hCG) test result within 28 days before randomization and agree to practice medically acceptable birth control during the course of the study. Medically acceptable birth control includes: surgical sterilization, hormonal contraceptives, barrier methods or an intrauterine device (IUD).
4. History of stable body weight, in the judgment of the investigator, for at least 6 months before randomization. No significant change, in the judgment of the investigator, in diet or exercise practices for at least 6 months before randomization and agreement to not change diet or exercise practices during the course of the study.
5. Expected to comply with and understand the visit schedule and all protocol-specified tests and procedures.
6. Medically able to undergo the administration of study material determined by clinical evaluations made within 56 days before and laboratory tests obtained within 28 days before randomization for which the investigator identified no clinically significant abnormality.
7. Signed informed consent obtained before any study-specific procedure is performed.

Exclusion Criteria:

1. History of any intervention to treat submental fat (e.g., liposuction, surgery, or lipolytic agents) or trauma associated with the chin or neck areas, which in the judgment of the investigator may affect evaluation of safety or efficacy of treatment.
2. Loose skin in the neck or chin area for which reduction in submental fat may, in the judgment of the investigator, result in an aesthetically unacceptable outcome or a score of 4 on the Skin Laxity Rating Scale (SLRS).
3. Prominent platysmal bands at rest or other anatomical features that, in the judgment of the investigator, may interfere with the evaluation of submental fat or result in an aesthetically unacceptable outcome.
4. Evidence of any cause of enlargement in the submental area (e.g., thyroid enlargement or cervical adenopathy) other than localized submental fat.
5. Body mass index (BMI) greater than 30.
6. Currently on or considering starting a weight reduction regimen.
7. Any medical condition (e.g., respiratory, cardiovascular, hepatic, neurological disease, uncontrolled hypertension, or thyroid dysfunction) that would interfere with assessment of safety or efficacy or compromise the subject's ability to undergo study procedures or provide informed consent.
8. Treatment with radio frequency, laser procedures, chemical peels, or dermal fillers in the neck or chin area within 12 months before randomization, or botulinum toxin injections in the neck or chin area within 6 months before randomization.
9. History of sensitivity to any components of the study material or to topical or local anesthetics (e.g., lidocaine, benzocaine, or novocaine).
10. Previous randomization into this study or previous treatment with ATX-101.
11. Treatment with an investigational device or agent within 30 days of randomization.

Participant flow

Outcome results

• Percentage of Participants With a Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) 1-grade Response (Primary), Number, percentage of participants: Deoxycholic Acid Injection 1 mg/cm² 58.3; Deoxycholic Acid Injection 2 mg/cm² 62.3; Placebo 34.5 (p <0.001)
• Percentage of Participants With a CR-SMFRS 2-grade Response (Secondary), Number, percentage of participants: Deoxycholic Acid Injection 1 mg/cm² 9.2; Deoxycholic Acid Injection 2 mg/cm² 9.0; Placebo 0.9 (p 0.020)
• Percentage of Participants With a Subject Self Rating Scale (SSRS) Response (Primary), Number, percentage of participants: Deoxycholic Acid Injection 1 mg/cm² 68.3; Deoxycholic Acid Injection 2 mg/cm² 64.8; Placebo 29.3 (p <0.001)
• Change From Baseline in CR-SMFRS Score (Secondary), Mean, units on a scale: Deoxycholic Acid Injection 1 mg/cm² -0.7 +/- 0.64; Deoxycholic Acid Injection 2 mg/cm² -0.8 +/- 0.61; Placebo -0.4 +/- 0.54 (p <0.001)
• Change From Baseline in SSRS Scores (Secondary), Mean, units on a scale: Deoxycholic Acid Injection 1 mg/cm² 2.9 +/- 1.61; Deoxycholic Acid Injection 2 mg/cm² 2.9 +/- 1.53; Placebo 1.5 +/- 1.69 (p <0.001)
• Change From Baseline in Submental Fat Thickness (Secondary), Mean, mm: Deoxycholic Acid Injection 1 mg/cm² -3.6 +/- 3.67; Deoxycholic Acid Injection 2 mg/cm² -3.8 +/- 4.41; Placebo -2.5 +/- 3.25 (p 0.090)
• Change From Baseline in Patient-reported Submental Fat Rating Scale (PR-SMFRS) (Secondary), Number, percentage of participants: Deoxycholic Acid Injection 1 mg/cm² 64.9; Deoxycholic Acid Injection 2 mg/cm² 67.3; Placebo 44.1 (p 0.009)
• Change From Baseline in Patient-Reported Submental Fat Impact Scale (PR-SMFIS) (Secondary)
• Change From Baseline in Self-rating of Attractiveness (Secondary), Mean, units on a scale: Deoxycholic Acid Injection 1 mg/cm² 0.6 +/- 1.37; Deoxycholic Acid Injection 2 mg/cm² 0.6 +/- 1.29; Placebo 0.3 +/- 1.33
• Change From Baseline in Derriford Appearance Scale 24 (DAS24) (Secondary)
• Change From Baseline in Body Image Quality of Life Inventory (BIQLI) (Secondary)

Adverse events

Time frame: From the first dose of study drug until 12 weeks after the last dose (up to 24 weeks after first treatment).

Serious adverse events by term

Other adverse events by term

• Frederick Beddingfield, MD, PhD, Study director, Kythera Biopharmaceuticals, Inc.