Open-Label Study of Deoxycholic Acid for the Reduction of Localized Subcutaneous Fat in the Submental Area

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kythera Biopharmaceuticals
ClinicalTrials.gov Identifier:
NCT01426373
First received: August 26, 2011
Last updated: December 8, 2015
Last verified: December 2015
  Purpose
To evaluate the safety of deoxycholic acid subcutaneous injections in the submental area (below the chin).

Condition Intervention Phase
Moderate or Severe Submental Fullness
Drug: Deoxycholic acid injection
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter, Open-label Study of ATX-101 (Sodium Deoxycholate Injection) for the Reduction of Localized Subcutaneous Fat in the Submental Area

Resource links provided by NLM:


Further study details as provided by Kythera Biopharmaceuticals:

Primary Outcome Measures:
  • Number of Participants With Adverse Events (AEs) [ Time Frame: Up to 12 months after last treatment (maximum of 18 months from first treatment) ] [ Designated as safety issue: No ]

    Serious AEs include any event that met one or more of the following criteria: was fatal or life-threatening, required inpatient hospitalization or prolonged a hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or a significant medical hazard.

    The severity of each AE was defined as either:

    Mild: The participant was aware of the sign or symptom, but it was easily tolerated.

    Moderate: The sign or symptom caused discomfort and interfered with usual activity.

    Severe: The sign or symptom was incapacitating, and the participant was unable to engage in usual activity.

    The investigator determined the relationship of each AE to the study drug using the question: "Is there a reasonable possibility that the event may have been caused by treatment with the study drug?"



Secondary Outcome Measures:
  • Mean Change From Baseline in Clinician-Reported Submental Fat Rating Scale Scores (CR-SMFRS) [ Time Frame: Baseline and months 3, 6, 9, and 12 after last treatment ] [ Designated as safety issue: No ]
    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 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = extreme). A negative change from baseline indicates improvement.

  • Mean Change From Baseline in Patient-Reported Submental Fat Scale Rating Scale (PR-SMFRS) [ Time Frame: Baseline and month 3 and month 12 after last treatment ] [ Designated as safety issue: No ]
    The PR-SMFRS is based on the participant's response to the question "How much fat do you have under your chin right now?" and answered on a 5-point ordinal scale (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.

  • Percentage of Participants Who Achieved a Composite 1-grade Response [ Time Frame: Baseline and month 3 and month 12 after last treatment ] [ Designated as safety issue: No ]

    A composite 1-grade response is defined as at least a 1-grade improvement from baseline on both the CR-SMFRS and PR-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 = 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?" and answered on a 5-point ordinal scale (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).


  • Percentage of Participants Who Achieved a Composite 2-grade Response [ Time Frame: Baseline and month 3 and month 12 after last treatment ] [ Designated as safety issue: No ]

    A composite 2-grade response is defined as at least a 2-grade improvement from baseline on both the CR-SMFRS and PR-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 = 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?" and answered on a 5-point ordinal scale (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).


  • Mean Change From Baseline in Patient-Reported Submental Fat Impact Scale (PR-SMFIS) [ Time Frame: Baseline and month 3 and month 12 after last treatment ] [ Designated as safety issue: No ]
    The PR-SMFIS assesses the impact of submental fat on self-perception of 6 emotional and visual characteristics (unhappy, bothered, self-conscious, embarrassed, look older, and look overweight) 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. 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.

  • Mean Change From Baseline in Subject Self Rating Scale (SSRS) [ Time Frame: Baseline and month 3 and month 12 after last treatment ] [ Designated as safety issue: No ]
    The SSRS assesses participants' satisfaction with their appearance in association with the face and chin on a 7-point scale from 0 to 6 (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.

  • Mean Change From Baseline in Self-rating of Attractiveness [ Time Frame: Baseline and month 3 and month 12 after last treatment ] [ Designated as safety issue: No ]
    Self-rating of Attractiveness assesses aspects of appearance from the participant's perspective with 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 (1 = not at all attractive, 5 = neither attractive nor unattractive, and 9 = extremely attractive). A positive change from baseline indicates improvement.

  • Response to Subject Global Questions [ Time Frame: Month 3 and month 12 after last treatment ] [ Designated as safety issue: No ]

    Participants answered 3 questions on a 7-point scale that ranged from "a great deal worse" to "a great deal better" (questions 1 and 2) or from "extremely dissatisfied" to "extremely satisfied" (question 3).

    Question 1: Since the start of the study, how would you rate the fat under your chin right now?

    Question 2: Since the start of the study, how would you rate the definition between your chin and neck right now?

    Question 3: How satisfied are you with the treatment you received in this study?


  • Percent Change From Baseline in Submental Fat Thickness [ Time Frame: Baseline and month 3 and month 12 after last treatment ] [ Designated as safety issue: No ]
    Submental fat thickness was measured using calipers.

  • Change From Baseline in Submental Skin Laxity Grade (SMSLG) [ Time Frame: Baseline and month 3 and month 12 after last treatment ] [ Designated as safety issue: No ]

    SMSLG assessment was based on clinical evaluation and palpation of the submental area. The SMSLG scale incorporates 3 features: skin wrinkling, adherence to underlying neck structures (bone and muscle) and redundancy (horizontal and vertical folds).

    Grade 1 (none): no or minimal superficial wrinkling, skin well apposed to deeper neck structures, no skin redundancy (no skin draping (vertical folds) or skin sagging (horizontal folds));

    Grade 2 (mild): mild superficial wrinkling, skin well apposed to deeper neck structures, minimal skin redundancy (slight skin draping and sagging);

    Grade 3 (moderate): may have mild to moderate superficial wrinkling, skin has mild to moderate separation from deeper neck structures, moderate skin redundancy (moderate skin draping and skin sagging);

    Grade 4 (severe): mild to marked superficial wrinkling, loose skin separated from deeper neck structures, marked skin redundancy (marked skin draping and sagging).


  • Change From Baseline in Line Drawing Assessment [ Time Frame: Baseline and month 3 after last treatment ] [ Designated as safety issue: No ]
    Each participant was given 2 example line drawings representing each of the 5 submental fat grades (0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = extreme) and asked to select the drawing that best represents their current profile. Improvement is any decrease in grade, and worsening is any increase in grade.


Enrollment: 165
Study Start Date: August 2011
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Deoxycholic Acid 2 mg/cm²
Participants received deoxycholic acid 2 mg/cm² administered in 0.2 mL injections, up to 10 mL per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.
Drug: Deoxycholic acid injection
Formulated as an injectable solution containing deoxycholic acid at a concentration of 10 mg/mL.
Other Names:
  • ATX-101
  • Kybella

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Submental fat graded by the investigator as 2, 3, or 4 using the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and graded by the subject as 2, 3, or 4 using the Patient-Reported Submental Fat Rating Scale (PR-SMFRS) as determined on visit 1 (within 28 days before the subject's first dosing session)
  • Dissatisfaction with the submental area rated by the subject as 0, 1, or 2 using the Subject Self-rating Scale (SSRS) as determined on visit 1 (within 28 days before the subject's first dosing session)
  • Males and nonpregnant, nonlactating females 18 years of age or greater, on the day of the subject's first dosing session (visit 2). Females of childbearing potential must have a negative human chorionic gonadotropin (serum) 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
  • A normal result on coagulation tests (prothrombin time (PT), partial thromboplastin time (PTT)) obtained within 28 days before subject's first dosing session
  • History of stable body weight, in the judgment of the investigator, for at least 6 months before subject's first dosing session
  • Expected to understand and 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
  • Medically able to undergo the administration of study drug determined by clinical and laboratory tests obtained within 28 days before subject's first dosing session for which the investigator identifies no clinically significant abnormality
  • Signed informed consent obtained before any study-specific procedure is performed

Exclusion Criteria:

  • History of any intervention to treat submental fat (eg, liposuction, surgery, or lipolytic agents)
  • History of trauma associated with the chin or neck areas, which in the judgment of the investigator may affect evaluation of safety or efficacy of treatment
  • A grade of 4 on the Submental Skin Laxity Grading scale (SMSLG) or any other anatomical feature (eg, predominant subplatysmal fat, loose skin in the neck or chin area, prominent platysmal bands) for which reduction in submental fat may, in the judgment of the investigator, result in an aesthetically unacceptable outcome
  • Evidence of any cause of enlargement in the submental area (eg, thyroid enlargement, cervical adenopathy) other than localized submental fat
  • Body mass index of ≥ 40 kg/m² as determined on visit 1 (week 0)
  • History or current symptoms of dysphagia
  • Any medical condition that would interfere with assessment of safety or efficacy or compromise the subject's ability to undergo study procedures or give informed consent
  • Treatment with radio frequency, laser procedures, chemical peels, or dermal fillers in the neck or chin area within 12 months before the first treatment session, or botulinum toxin injections in the neck or chin area within 6 months before the first treatment session
  • History of sensitivity to any components of the study drug or to topical or local anesthetics (eg, lidocaine, benzocaine, novocaine)
  • Previous treatment in this study or previous participation in a Kythera-sponsored ATX-101 study
  • Treatment with an investigational device or agent within 30 days before the subject's first treatment session
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01426373

Locations
United States, California
Mark Rubin
Beverly Hills, California, United States, 90212
Mitchel Goldman
LaJolla, California, United States, 92121
Jeffrey Klein
San Juan Capistrano, California, United States, 92675
Ava Shamban
Santa Monica, California, United States, 90404
Steven Teitelbaum
Santa Monica, California, United States, 90404
United States, Florida
Susan Weinkle
Bradenton, Florida, United States, 34209
Palm Beach Cosmetic
West Palm Beach, Florida, United States, 33401
United States, Illinois
Steven Dayan
Chicago, Illinois, United States, 60611
United States, Louisiana
Lupo Center for Aesthetic and General Dermatology
New Orleans, Louisiana, United States, 70124
United States, Michigan
Grekin Skin Institute
Warren, Michigan, United States, 48088
United States, New Jersey
David Goldberg, MD
Hillsborough, New Jersey, United States, 08844
United States, New York
Roy Geronemus, MD
New York, New York, United States, 10016
Macrene Alexiades-Armenakas
New York, New York, United States, 10028
United States, North Carolina
Sue Ellen Cox
Chapel Hill, North Carolina, United States, 27517
United States, Pennsylvania
Richard Fried
Yardley, Pennsylvania, United States, 19067
United States, Tennessee
Michael Gold
Nashville, Tennessee, United States, 37215
United States, Texas
Suzanne Bruce
Houston, Texas, United States, 77056
Jeffrey Adelglass
Plano, Texas, United States, 75093
Sponsors and Collaborators
Kythera Biopharmaceuticals
Investigators
Study Director: Frederick Beddingfield, III, M.D., PhD Kythera Biopharmaceuticals, Inc
  More Information

Responsible Party: Kythera Biopharmaceuticals
ClinicalTrials.gov Identifier: NCT01426373     History of Changes
Other Study ID Numbers: ATX-101-11-26 
Study First Received: August 26, 2011
Results First Received: December 8, 2015
Last Updated: December 8, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Deoxycholic Acid
Cholagogues and Choleretics
Gastrointestinal Agents

ClinicalTrials.gov processed this record on August 25, 2016