Patient Experience Study of Deoxycholic Acid Injection

Study Overview
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Brief Summary
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The objectives of this study are to determine the safety of deoxycholic acid subcutaneous (SC) injections in the submental area and to evaluate the effects of four interventions, relative to placebo in the submental area, particularly with regard to assessment and management of pain, bruising, and swelling/edema.

Detailed Description
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This study evaluated the effects of four interventions, pre- and post-subcutaneous injections of deoxycholic acid injection relative to placebo in adults with submental fullness. Participants were randomized to either deoxycholic acid injection or placebo in a ratio of 4:1 and to one of four patient experience management paradigms. Participants were required to visit the research facility on 10 separate occasions for protocol-defined treatments, procedures, tests, and observations.

Official Title
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A Single Center, Double-blind, Parallel-group, Two Factor Patient-Experience Management Study of ATX-101 (Deoxycholic Acid Injection) for the Reduction of Localized Subcutaneous Fat in the Submental Area

Conditions
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Moderate or Severe Submental Fullness

Intervention / Treatment
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* Drug: Deoxycholic Acid Injection
* Drug: Placebo
* Other: Cold Compress
* Drug: Lidocaine / Epinephrine
* Drug: Loratadine
* Drug: Ibuprofen
* Other: Compression Chin Strap


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Submental fat graded by the Investigator as 2 (moderate) or 3 (severe) using the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and graded by the subject as 2 (moderate amount) or 3 (large amount) using the Patient-Reported Submental Fat Rating Scale (PR-SMFRS) Dissatisfaction with the appearance of the submental area expressed by the subject as a rating of 0, 1, or 2 using the Subject Self Rating Scale (SSRS) History of stable body weight for at least 6 months and body mass index (BMI) of ≤ 40 kg/m². Acceptable skin laxity as determined by the investigator Agreement by the subject to refrain from making significant changes, in the documented judgment of the investigator, to his or her dietary or exercise habits during the course of the subject's participation. Agreement to forego any treatment or behavior (e.g., unshaven facial hair) Signed informed consent obtained before any study-specific procedure is performed. Exclusion Criteria: No prior intervention for submental fullness or recent cosmetic procedure in the neck or chin area Absence of clinically significant health problems Body mass index > 40.0 kg/m² as determined prior to randomization. History of drug or alcohol abuse.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paradigm 1 / Deoxycholic Acid Injection<br>Participants received deoxycholic acid 2 mg/cm² administered in 0.2 mL injections, either 6 or 8 mL (based on Baseline CR-SMFRS grade 2 or 3, respectively) on Day 0 and a cold compress applied to the treatment area. | Drug: Deoxycholic Acid Injection<br>* Formulated as an injectable solution containing deoxycholic acid at a concentration of 10 mg/mL.<br>* Other names: Kybella;Other: Cold Compress<br>* A cold compress was applied to the injection area for 10 minutes before dosing and for 15 minutes after dosing.<br>|
| Placebo Comparator: Paradigm 1/ Placebo<br>Participants received placebo administered in 0.2 mL injections, either 6 or 8 mL on Day 0 and a cold compress applied to the treatment area. | Drug: Placebo<br>* Phosphate buffered saline placebo for injection<br>Other: Cold Compress<br>* A cold compress was applied to the injection area for 10 minutes before dosing and for 15 minutes after dosing.<br>|
| Experimental: Paradigm 2 / Deoxycholic Acid Injection<br>Participants received deoxycholic acid 2 mg/cm² administered in 0.2 mL injections, either 6 or 8 mL on Day 0, topical and injectable anesthetics (lidocaine/epinephrine) and a cold compress applied to the treatment area. | Drug: Deoxycholic Acid Injection<br>* Formulated as an injectable solution containing deoxycholic acid at a concentration of 10 mg/mL.<br>* Other names: Kybella;Other: Cold Compress<br>* A cold compress was applied to the injection area for 10 minutes before dosing and for 15 minutes after dosing.<br>Drug: Lidocaine / Epinephrine<br>* Lidocaine 4% topical cream applied 45 minutes prior to dosing across the area to be treated, followed by 0.4 mL SC injections of lidocaine HCl 1% / epinephrine 1:100,000 around the perimeter of the treatment area and across the treatment area in a regular pattern 25 minutes before dosing.<br>|
| Placebo Comparator: Paradigm 2 / Placebo<br>Participants received placebo administered in 0.2 mL injections, either 6 or 8 mL on Day 0, topical and injectable anesthetics and a cold compress applied to the treatment area. | Drug: Placebo<br>* Phosphate buffered saline placebo for injection<br>Other: Cold Compress<br>* A cold compress was applied to the injection area for 10 minutes before dosing and for 15 minutes after dosing.<br>Drug: Lidocaine / Epinephrine<br>* Lidocaine 4% topical cream applied 45 minutes prior to dosing across the area to be treated, followed by 0.4 mL SC injections of lidocaine HCl 1% / epinephrine 1:100,000 around the perimeter of the treatment area and across the treatment area in a regular pattern 25 minutes before dosing.<br>|
| Experimental: Paradigm 3 / Deoxycholic Acid Injection<br>Participants received deoxycholic acid 2 mg/cm² administered in 0.2 mL injections, either 6 or 8 mL on Day 0, oral antihistamine and anti-inflammatory agents (loratadine and ibuprofen), topical and injectable anesthetics and a cold compress applied to the treatment area. | Drug: Deoxycholic Acid Injection<br>* Formulated as an injectable solution containing deoxycholic acid at a concentration of 10 mg/mL.<br>* Other names: Kybella;Other: Cold Compress<br>* A cold compress was applied to the injection area for 10 minutes before dosing and for 15 minutes after dosing.<br>Drug: Lidocaine / Epinephrine<br>* Lidocaine 4% topical cream applied 45 minutes prior to dosing across the area to be treated, followed by 0.4 mL SC injections of lidocaine HCl 1% / epinephrine 1:100,000 around the perimeter of the treatment area and across the treatment area in a regular pattern 25 minutes before dosing.<br>Drug: Loratadine<br>* Loratadine 10 mg orally from Day -7 until Day 7<br>Drug: Ibuprofen<br>* Ibuprofen 600 mg at least 1 hour prior to dosing and 600 mg 3 times a day for at least 3 days after dosing.<br>|
| Placebo Comparator: Paradigm 3 / Placebo<br>Participants received placebo administered in 0.2 mL injections, either 6 or 8 mL on Day 0, oral antihistamine and anti-inflammatory agents, topical and injectable anesthetics and a cold compress applied to the treatment area. | Drug: Placebo<br>* Phosphate buffered saline placebo for injection<br>Other: Cold Compress<br>* A cold compress was applied to the injection area for 10 minutes before dosing and for 15 minutes after dosing.<br>Drug: Lidocaine / Epinephrine<br>* Lidocaine 4% topical cream applied 45 minutes prior to dosing across the area to be treated, followed by 0.4 mL SC injections of lidocaine HCl 1% / epinephrine 1:100,000 around the perimeter of the treatment area and across the treatment area in a regular pattern 25 minutes before dosing.<br>Drug: Loratadine<br>* Loratadine 10 mg orally from Day -7 until Day 7<br>Drug: Ibuprofen<br>* Ibuprofen 600 mg at least 1 hour prior to dosing and 600 mg 3 times a day for at least 3 days after dosing.<br>|
| Experimental: Paradigm 4 / Deoxycholic Acid Injection<br>Participants received deoxycholic acid 2 mg/cm² administered in 0.2 mL injections, either 6 or 8 mL on Day 0, a compression chin strap, oral antihistamine and anti-inflammatory agents, topical and injectable anesthetics and a cold compress applied to the treatment area. | Drug: Deoxycholic Acid Injection<br>* Formulated as an injectable solution containing deoxycholic acid at a concentration of 10 mg/mL.<br>* Other names: Kybella;Other: Cold Compress<br>* A cold compress was applied to the injection area for 10 minutes before dosing and for 15 minutes after dosing.<br>Drug: Lidocaine / Epinephrine<br>* Lidocaine 4% topical cream applied 45 minutes prior to dosing across the area to be treated, followed by 0.4 mL SC injections of lidocaine HCl 1% / epinephrine 1:100,000 around the perimeter of the treatment area and across the treatment area in a regular pattern 25 minutes before dosing.<br>Drug: Loratadine<br>* Loratadine 10 mg orally from Day -7 until Day 7<br>Drug: Ibuprofen<br>* Ibuprofen 600 mg at least 1 hour prior to dosing and 600 mg 3 times a day for at least 3 days after dosing.<br>Other: Compression Chin Strap<br>* A compression chin strap was applied 15 minutes after dosing for at least 24 hours.<br>|
| Placebo Comparator: Paradigm 4 / Placebo<br>Participants received placebo administered in 0.2 mL injections, either 6 or 8 mL on Day 0, a compression chin strap, oral antihistamine and anti-inflammatory agents, topical and injectable anesthetics and a cold compress applied to the treatment area. | Drug: Placebo<br>* Phosphate buffered saline placebo for injection<br>Other: Cold Compress<br>* A cold compress was applied to the injection area for 10 minutes before dosing and for 15 minutes after dosing.<br>Drug: Lidocaine / Epinephrine<br>* Lidocaine 4% topical cream applied 45 minutes prior to dosing across the area to be treated, followed by 0.4 mL SC injections of lidocaine HCl 1% / epinephrine 1:100,000 around the perimeter of the treatment area and across the treatment area in a regular pattern 25 minutes before dosing.<br>Drug: Loratadine<br>* Loratadine 10 mg orally from Day -7 until Day 7<br>Drug: Ibuprofen<br>* Ibuprofen 600 mg at least 1 hour prior to dosing and 600 mg 3 times a day for at least 3 days after dosing.<br>Other: Compression Chin Strap<br>* A compression chin strap was applied 15 minutes after dosing for at least 24 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Pain Visual Analog Scale Scores | Participants were provided with a scale 100 mm in length and were asked to mark the place on the line that best represents his or her pain associated with the area treated with study drug. The scale ranged from 0 (no pain) to 100 (most severe pain possible). | Baseline and Day 84 | 
| Change From Baseline in Pain Assessment Using McGill Pain Questionnaire | Participants rated 15 pain characteristics by using a number to signify how much of that specific type of pain they were experiencing using the Short-Form McGill Pain Questionnaire. The pain characteristic options included Throbbing, Shooting, Stabbing, Sharp, Cramping, Gnawing, Hot-burning, Aching, Heavy, Tender, Splitting, Tiring-exhausting, Sickening, Fearful, and Punishing- cruel. Participants assessed the intensity of each characteristic using the following score system: none (0), mild (1), moderate (2), and severe (3). In addition, present pain was assessed on a scale from 0 (no pain) to 5 (excruciating). | Baseline (predose) and Day 84 | 
| Swelling Grading Scale Scores | The following grading system was used for the assessment of swelling: Swelling/edema absent (0) Minimal swelling/edema contained within treatment area (1) Modest swelling/edema contained within treatment area (2) Substantial swelling/edema contained within treatment area (3) Swelling/edema of the neck and face beyond the treatment area (4) | Day 84 | 
| Bruising Grading Scale Scores | The following grading system was used for the assessment of bruising: Bruising absent (0) Bruising associated with 1 to 3 needle insertion points (1) Bruising spreading beyond 4 or more individual needle insertion points but contained within the treatment area (2) Bruising covering the entire treatment area but contained within the treatment area (3) Bruising of the neck and face beyond the treatment area (4) | Day 84 | 
| Induration Grading Scale Scores | The following grading system was used for the assessment of induration: Induration absent to minimal (0) Induration associated with at least approximately 30% of the treatment area (1) Induration associated with greater than approximately 30% to at least 60% of the treatment area (2) Induration covering the entire treatment area but contained within the treatment area (3) Induration of the neck and face beyond the treatment area (4) | Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Clinician-Reported Submental Fat Rating Scale (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 (0-4) with 0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = extreme. A negative change from Baseline indicates improvement. | Baseline and Day 84 | 
| Change From Baseline in Patient-Reported Submental Fat 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? 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. A negative change from Baseline indicates improvement. | Baseline and Day 84 | 
| Change From Baseline in Subject Self Rating Scale (SSRS) | 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. | Baseline and Day 84 | 
| Change From Baseline in Submental Skin Laxity Grades (SMSLG) | Skin laxity assessment was based on clinical evaluation and palpation of the submental area on the following scale: 1 = no laxity; 2 = mild laxity; 3 = moderate laxity; 4 = severe laxity. A negative change from Baseline indicates improvement. | Baseline and Day 84 | 
| Change From Baseline in Submental Fat Thickness | Submental thickness was measured using caliper devices. | Baseline and Day 84 | 
| Patient Experience Questions | Participants were asked to complete 3 patient experience questions, each answered as Yes or No: Given your experience in this study: Would you recommend this procedure to a friend? Would you agree to receive additional treatments? Has the treatment you received in this study affected your normal activities? The percentage of participants answering Yes on each question is reported. | Day 84 |