Phase 2 Study of Deoxycholic Acid Injection (ATX-101) for the Reduction of Submental Fat

Study Overview
=================
Brief Summary
-----------------
Phase 2 trial to evaluate the safety and potential efficacy of one concentration of deoxycholic acid injection, given in three dosing paradigms, compared to placebo for the reduction of submental fat (fat beneath the chin).

Official Title
-----------------
Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of the Safety and Efficacy of ATX-101 (Sodium Deoxycholate for Injection) Given by Three Dosing Paradigms for the Reduction of Localized Subcutaneous Fat in the Submental Area

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

Intervention / Treatment
-----------------
* Drug: Deoxycholic Acid Injection
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Submental fat that was considered undesirable by the subject and graded by the investigator as 2 or 3 using the submental fat (SMF) rating scale Good general health Signed informed consent Exclusion Criteria: History of any treatment in the neck or chin area Loose skin or prominent platysmal bands in the neck or chin area Recent treatment with anticoagulants Presence of clinically significant health problems

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 65 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deoxycholic Acid Injection 0.2 mL/0.7 cm<br>Participants received deoxycholic acid administered in 0.2 mL injections, 0.7 cm apart, up to 9.6 mL per treatment session at intervals of approximately 1 month for up to a maximum of 4 treatments. | Drug: Deoxycholic Acid Injection<br>* Formulated as an injectable solution containing deoxycholic acid at a concentration of 10 mg/mL.<br>* Other names: ATX-101;|
| Placebo Comparator: Placebo 0.2 mL/0.7 cm<br>Participants received placebo administered in 0.2 mL injections, 0.7 cm apart, up to 9.6 mL per treatment session at intervals of approximately 1 month for up to a maximum of 4 treatments. | Drug: Placebo<br> <br> |
| Experimental: Deoxycholic Acid Injection 0.2 mL/1.0 cm<br>Participants received deoxycholic acid administered in 0.2 mL injections, 1.0 cm apart, up to 4.8 mL per treatment session at intervals of approximately 1 month for up to a maximum of 4 treatments. | Drug: Deoxycholic Acid Injection<br>* Formulated as an injectable solution containing deoxycholic acid at a concentration of 10 mg/mL.<br>* Other names: ATX-101;|
| Placebo Comparator: Placebo 0.2 mL/1.0 cm<br>Participants received placebo administered in 0.2 mL injections, 1.0 cm apart, up to 4.8 mL per treatment session at intervals of approximately 1 month for up to a maximum of 4 treatments. | Drug: Placebo<br> <br> |
| Experimental: Deoxycholic Acid Injection 0.4 mL/1.0 cm<br>Participants received deoxycholic acid administered in 0.4 mL injections, 1.0 cm apart, up to 9.6 mL per treatment session at intervals of approximately 1 month for up to a maximum of 4 treatments. | Drug: Deoxycholic Acid Injection<br>* Formulated as an injectable solution containing deoxycholic acid at a concentration of 10 mg/mL.<br>* Other names: ATX-101;|
| Placebo Comparator: Placebo 0.4 mL/1.0 cm<br>Participants received placebo administered in 0.4 mL injections, 1.0 cm apart, up to 9.6 mL per treatment session at intervals of approximately 1 month for up to a maximum of 4 treatments. | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | The investigator determined the relationship of each adverse event to the administration of study drug. Severity of adverse events was determined using the following scale: Mild: The participant is aware of a sign or symptom, but it is easily tolerated Moderate: Discomfort or interference with usual activity Severe: Incapacitating, with inability to engage in usual activity. A serious AE (SAE) was defined as an event that may constitute a significant medical hazard or side-effect, regardless of the investigator or sponsor's opinion regarding relatedness to study material. Serious events included, but were not limited to, any event that: was fatal was life-threatening required inpatient hospitalization or prolongation of existing hospitalization resulted in persistent or significant disability/incapacity was a congenital anomaly/birth defect other significant medical hazard | From the first dose of study drug until 12 weeks after the last dose (up to 24 weeks after first treatment). | 
| Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, Weight, Vital Signs, and Physical Examinations |  | From the first dose of study drug until 12 weeks after the last dose (up to 24 weeks after first treatment). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Submental Fat (SMF) Rating Scale Score | The SMF rating scale 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. | Baseline and 4 weeks after last treatment (up to 16 weeks after first dose) | 
| Change From Baseline in Subject Satisfaction With Appearance Rating Scale | The Subject Satisfaction with Appearance Rating Scale assesses participants' 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. | Baseline and 4 weeks after last treatment (up to 16 weeks after first dose) | 
| Percentage of Participants With a Response in the Subject Global Improvement Rating | Participants were asked to rate their total improvement or worsening in the appearance and physical feeling of their chin and neck area since before they received study treatment, whether or not they believed it was due to study treatment or to any other cause. 0 = Very much worse, 1 = Much worse, 2 = Minimally worse, 3 = No change, 4 = Minimally improved, 5 = Much improved, 6 = Very much improved. Response is defined as any improvement, ie, a global improvement rating of 4, 5, or 6. | 4 weeks after last treatment (up to 16 weeks after first dose) | 
| Percentage of Participants With an SMF Response | Response is defined as a participant with at least a 1-grade improvement in SMF Rating Scale score at Week 16 from Baseline. The SMF rating scale 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. | Baseline and 4 weeks after last treatment (up to 16 weeks after first dose) | 
| Change From Baseline in Skin Laxity Rating | Skin laxity assessment was based on clinical evaluation and palpation of the submental area on the following scale: 1 = no laxity; 2 = minimal laxity; 3 = moderate laxity; 4 = very lax. A negative change from Baseline indicates improvement. | Baseline and Week 4, Week 8, Week 12, Week 16 (4 weeks after last treatment) and Week 24 (12 weeks after last treatment) | 
| Change From Baseline to Each Visit in Submental Fat (SMF) Rating Scale Score | The SMF rating scale 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. | Baseline and Week 4, Week 8, Week 12, Week 16 (4 weeks after last treatment) and Week 24 (12 weeks after last treatment) | 
| Change From Baseline in the Cervicomental Angle | The cervicomental angle was measured using a profile view photograph obtained at each visit. A goniometer was used to determine the angle. Cervicomental angle measurements less than 80 degrees are excluded, due to error in measurement. | Baseline and 4 weeks after last treatment (up to 16 weeks after first dose) | 
| Visual Analogue Scale Pain Intensity Rating | Participants rated pain associated with the submental area on a 100 mm horizontal axis ranging from 0 (no pain) to 100 (most severe pain possible) | Approximately 60 minutes after completion of each treatment session at Week 0, Week 4, Week 8 and Week 12 |