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

• Deoxycholic Acid Injection (Drug), also known as ATX-101: Formulated as an injectable solution containing deoxycholic acid at a concentration of 10 mg/mL.
• Placebo (Drug)

Primary outcomes

• Number of Participants With Adverse Events [From the first dose of study drug until 12 weeks after the last dose (up to 24 weeks after first treatment).]: 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
• 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 outcomes

• Change From Baseline in Submental Fat (SMF) Rating Scale Score [Baseline and 4 weeks after last treatment (up to 16 weeks after first dose)]: 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.
• Change From Baseline in Subject Satisfaction With Appearance Rating Scale [Baseline and 4 weeks after last treatment (up to 16 weeks after first dose)]: 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.
• Percentage of Participants With a Response in the Subject Global Improvement Rating [4 weeks after last treatment (up to 16 weeks after first dose)]: 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.
• Percentage of Participants With an SMF Response [Baseline and 4 weeks after last treatment (up to 16 weeks after first dose)]: 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.
• Change From Baseline in Skin Laxity Rating [Baseline and Week 4, Week 8, Week 12, Week 16 (4 weeks after last treatment) and Week 24 (12 weeks after last treatment)]: 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.
• Change From Baseline to Each Visit in Submental Fat (SMF) Rating Scale Score [Baseline and Week 4, Week 8, Week 12, Week 16 (4 weeks after last treatment) and Week 24 (12 weeks after last treatment)]: 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.
• Change From Baseline in the Cervicomental Angle [Baseline and 4 weeks after last treatment (up to 16 weeks after first dose)]: 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.
• Visual Analogue Scale Pain Intensity Rating [Approximately 60 minutes after completion of each treatment session at Week 0, Week 4, Week 8 and Week 12]: 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)

Sex: All, ages: 25 Years to 65 Years

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

Participant flow

Outcome results

• Number of Participants With Adverse Events (Primary), Number, participants: Deoxycholic Acid Injection 0.2 mL/0.7 cm 24; Deoxycholic Acid Injection 0.2 mL/1.0 cm 13; 0Deoxycholic Acid Injection 0.4 mL/1.0 cm 20; Pooled Placebo 14
• Change From Baseline in Submental Fat (SMF) Rating Scale Score (Secondary), Mean, units on a scale: Deoxycholic Acid Injection 0.2 mL/0.7 cm -1.0 +/- 0.58; Deoxycholic Acid Injection 0.2 mL/1.0 cm -1.2 +/- 0.63; Deoxycholic Acid Injection 0.4 mL/1.0 cm -0.8 +/- 0.72; Pooled Placebo -0.4 +/- 0.50 (p 0.005)
• Change From Baseline in Subject Satisfaction With Appearance Rating Scale (Secondary), Mean, units on a scale: Deoxycholic Acid Injection 0.2 mL/0.7 cm 3.5 +/- 1.47; Deoxycholic Acid Injection 0.2 mL/1.0 cm 4.3 +/- 1.34; Deoxycholic Acid Injection 0.4 mL/1.0 cm 2.8 +/- 2.20; Pooled Placebo 1.8 +/- 1.72 (p 0.005)
• Percentage of Participants With a Response in the Subject Global Improvement Rating (Secondary), Number, percentage of participants: Deoxycholic Acid Injection 0.2 mL/0.7 cm 95.5; Deoxycholic Acid Injection 0.2 mL/1.0 cm 90.0; Deoxycholic Acid Injection 0.4 mL/1.0 cm 80.0; Pooled Placebo 57.1 (p 0.008)
• Percentage of Participants With an SMF Response (Secondary), Number, percentage of participants: Deoxycholic Acid Injection 0.2 mL/0.7 cm 81.8; Deoxycholic Acid Injection 0.2 mL/1.0 cm 90.0; Deoxycholic Acid Injection 0.4 mL/1.0 cm 60.0; Pooled Placebo 35.7 (p 0.011)
• Change From Baseline in Skin Laxity Rating (Secondary), Mean, units on a scale: Deoxycholic Acid Injection 0.2 mL/0.7 cm -0.1 +/- 0.34; Deoxycholic Acid Injection 0.2 mL/1.0 cm -0.1 +/- 0.64; Deoxycholic Acid Injection 0.4 mL/1.0 cm -0.2 +/- 0.54; Pooled Placebo 0.0 +/- 0.78 (p 0.460)
• Change From Baseline to Each Visit in Submental Fat (SMF) Rating Scale Score (Secondary), Mean, units on a scale: Deoxycholic Acid Injection 0.2 mL/0.7 cm -0.3 +/- 0.57; Deoxycholic Acid Injection 0.2 mL/1.0 cm -0.5 +/- 0.52; Deoxycholic Acid Injection 0.4 mL/1.0 cm -0.1 +/- 0.32; Pooled Placebo -0.3 +/- 0.47 (p 0.934)
• Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, Weight, Vital Signs, and Physical Examinations (Primary), Number, participants: Deoxycholic Acid Injection 0.2 mL/0.7 cm 3; Deoxycholic Acid Injection 0.2 mL/1.0 cm 0; Deoxycholic Acid Injection 0.4 mL/1.0 cm 2; Pooled Placebo 0
• Change From Baseline in the Cervicomental Angle (Secondary), Mean, degrees: Deoxycholic Acid Injection 0.2 mL/0.7 cm -5.0 +/- 9.85; Deoxycholic Acid Injection 0.2 mL/1.0 cm -1.5 +/- 7.84; Deoxycholic Acid Injection 0.4 mL/1.0 cm -1.5 +/- 10.40; Pooled Placebo -2.7 +/- 7.80 (p 0.573)
• Visual Analogue Scale Pain Intensity Rating (Secondary), Mean, units on a scale: Deoxycholic Acid Injection 0.2 mL/0.7 cm 33.0 +/- 27.29; Deoxycholic Acid Injection 0.2 mL/1.0 cm 25.8 +/- 16.19; Deoxycholic Acid Injection 0.4 mL/1.0 cm 41.9 +/- 27.50; Pooled Placebo 17.1 +/- 19.03

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

12 more terms not shown.

• Frederick Beddingfield, III, M.D., Ph.D., Study director, Kythera Biopharmaceuticals, Inc.