Phase 3 Study of Deoxycholic Acid Injection (ATX-101) Versus Placebo for the Reduction of Localized Subcutaneous Fat in the Submental Area

Moderate or Severe Submental Fullness Clinical Trial

— REFINE-1  

Official title:

Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ATX-101 (Sodium Deoxycholate Injection) Versus Placebo for the Reduction of Localized Subcutaneous Fat in the Submental Area

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01542034
• Other study ID #: ATX-101-11-22
• Status: Completed
• Phase: Phase 3
• First received: February 24, 2012
• Last updated: May 28, 2015
• Start date: February 2012
• Est. completion date: August 2013

Study information

• Verified date: May 2015
• Source: Kythera Biopharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To evaluate the safety and efficacy of deoxycholic acid injection in the reduction of submental fat (fat below the chin).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 506
• Est. completion date: August 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Submental fat graded by the investigator as 2 or 3 using the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and graded by the subject as 2 or 3 using the Patient-Reported Submental Fat Rating Scale (PR-SMFRS) as determined on Visit 1 (within 28 days before randomization).

2. Dissatisfaction with the submental area expressed by the subject as a rating of 0, 1, or 2 using the Subject Self Rating Scale (SSRS) as determined on Visit 1 (within 28 days before randomization).

3. Males and nonpregnant, nonlactating females 18 to 65 years of age, inclusive, on the day of randomization (Visit 2). Females of childbearing potential must have a negative human chorionic gonadotropin (hCG) 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. Females of childbearing potential who are not sexually active need not practice contraception.

4. History of stable body weight, in the judgment of the investigator, for at least 6 months before randomization.

5. Expected to understand and agree to 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.

6. Agreement to forego any treatment or behavior (e.g., unshaven facial hair) during the subject's participation in the study that may affect the assessments of the submental area.

7. Medically able to undergo the administration of study material determined by clinical and laboratory tests obtained within 28 days before randomization for which the investigator identified no clinically significant abnormality.

8. 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).

2. History of trauma associated with the chin or neck areas that in the judgment of the investigator may affect evaluation of safety or efficacy of treatment.

3. A Submental Skin Laxity Grade (SMSLG) of 4 or other anatomical feature (e.g., predominant subplatysmal fat, loose skin in the neck or chin area, prominent platysmal bands), as assessed within 28 days before randomization, for which reduction in submental fat may, in the judgment of the investigator, result in an aesthetically unacceptable outcome.

4. Evidence of any cause of enlargement in the submental area (e.g., thyroid enlargement, cervical adenopathy) other than localized submental fat.

5. Body mass index of > 40.0 as determined on Visit 1.

6. History or current symptoms of dysphagia.

7. A result on coagulation tests (PT, PTT) obtained within 28 days before randomization that indicates the presence of any clinically significant bleeding disorder.

8. Any medical condition (e.g., respiratory, cardiovascular, hepatic, neurological disease, or thyroid dysfunction) that would interfere with assessment of safety or efficacy or compromise the subject's ability to undergo study procedures or give informed consent.

9. Treatment with radio frequency, laser procedures, chemical peels, or dermal fillers in the neck or chin area within 12 months before randomization.

10. Treatment with botulinum toxin injections in the neck or chin area within 6 months before randomization.

11. History of sensitivity to any components of the study material

12. History of sensitivity to topical or local anesthetics (e.g., lidocaine, benzocaine, procaine).

13. Previous randomization in this study or previous participation in a Kythera-sponsored ATX 101 trial.

14. Treatment with an investigational device or agent within 30 days before randomization.

15. For centers selected to conduct magnetic resonance imaging (MRI) evaluations, any subject with the presence of any condition that would render a subject unsuitable for MRI evaluation (e.g., claustrophobia), or metals in the body that would interfere with MRI acquisition (e.g., nonremovable metal appliances in the mouth such as silver or gold caps, pacemakers, metal joints).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Moderate or Severe Submental Fullness

Intervention

Drug:
• Deoxycholic acid injection
Formulated as an injectable solution containing deoxycholic acid at a concentration of 10 mg/mL.
• Placebo
Phosphate buffered saline placebo for injection

Locations

Country	Name	City	State
Canada	Investigational Site	Montreal	Quebec
Canada	Investigational Site	Peterborough	Ontario
Canada	Investigational Site	Toranto	Ontario
Canada	Investigational Site	Toronto	Ontario
Canada	Investigational Site	Vancouver, B.C.
United States	Investigational Site	Arlington	Illinois
United States	Investigational Site	Atlanta	Georgia
United States	Investigational Site	Beverly Hills	California
United States	Investigational Site	Beverly Hills	California
United States	Investigational Site	Birmingham	Alabama
United States	Investigational Site	Charlotte	North Carolina
United States	Investigational Site	Charlottesville	Virginia
United States	Investigational Site	Chicago	Illinois
United States	Investigational Site	Evansville	Indiana
United States	Investigational Site	Fridley	Minnesota
United States	Investigational Site	Glen Dale	Maryland
United States	Investigational Site	Hunt Valley	Maryland
United States	Investigational Site	Irvine	California
United States	Investigational Site	Los Angeles	California
United States	Investigational Site	Louisville	Kentucky
United States	Investigational Site	Miami Beach	Florida
United States	Investigational Site	Nashville	Tennessee
United States	Investigational Site	Nashville	Tennessee
United States	Investigational Site	New Haven	Connecticut
United States	Investigational Site	New York	New York
United States	Investigational Site	New York	New York
United States	Investigational Site	Oceanside	California
United States	Investigational Site	Omaha	Nebraska
United States	Investigational Site	Rockville	Maryland
United States	Investigational Site	San Diego	California
United States	Investigational Site	SanDiego	California
United States	Investigational Site	Snellville	Georgia
United States	Investigational Site	Spokane	Washington
United States	Investigational Site	Washington	District of Columbia
United States	Investigational Site	West Bloomfield	Michigan
United States	Investigational Site	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Kythera Biopharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and Patient-Reported Submental Fat Rating Scale (PR-SMFRS) 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.; 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.	Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment)	No
Primary	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 Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and Patient-Reported Submental Fat Rating Scale (PR-SMFRS) 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.; 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.	Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment)	No
Secondary	Percentage of Participants With a Magnetic Resonance Imaging (MRI) Response	An MRI responder is a participant who exhibited at least a 10% reduction in submental fat volume as measured by MRI from Baseline to 12 weeks after last treatment. Magnetic resonance imaging was evaluated in a subset of participants at selected centers.	Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment)	No
Secondary	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 related to the appearance of submental fullness (unhappy, bothered, self-conscious, embarrassed, look older, and look overweight) 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 12 weeks after last treatment (up to 32 weeks after first treatment)	No