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Phase 3 Study of Deoxycholic Acid Injection (ATX-101) Versus Placebo for the Reduction of Localized Subcutaneous Fat in the Submental Area (REFINE-1)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01542034
First Posted: March 1, 2012
Last Update Posted: June 15, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Kythera Biopharmaceuticals
Results First Submitted: May 28, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition: Moderate or Severe Submental Fullness
Interventions: Drug: Deoxycholic acid injection
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was performed at 35 investigational centers in the United States (US) and Canada.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Deoxycholic Acid Injection 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.
Placebo Participants received placebo 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.

Participant Flow:   Overall Study
    Deoxycholic Acid Injection   Placebo
STARTED   256   250 
Received Treatment   256   249 
COMPLETED   226 [1]   227 [1] 
NOT COMPLETED   30   23 
Consent Withdrawn (Subject Convenience)                20                12 
Administrative decision                0                3 
Subject Noncompliance                1                0 
Adverse Event                2                2 
Lost to Follow-up                7                6 
[1] Participants who completed long-term follow-up 24 weeks after the last treatment



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention-to-treat population

Reporting Groups
  Description
Deoxycholic Acid Injection 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.
Placebo Participants received placebo 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.
Total Total of all reporting groups

Baseline Measures
   Deoxycholic Acid Injection   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 256   250   506 
Age 
[Units: Years]
Mean (Standard Deviation)
 49.5  (9.30)   49.4  (9.33)   49.5  (9.30) 
Age, Customized 
[Units: Participants]
     
18 - 50 years   122   121   243 
51 - 65 years   134   129   263 
Gender 
[Units: Participants]
     
Female   213   208   421 
Male   43   42   85 
Race/Ethnicity, Customized 
[Units: Participants]
     
White   218   227   445 
Black or African American   24   13   37 
Asian   7   5   12 
American Indian or Alaskan Native   0   2   2 
Native Hawaiian or Pacific Islander   0   1   1 
Multiple   2   0   2 
Other   5   2   7 
Race/Ethnicity, Customized 
[Units: Participants]
     
Hispanic or Latino   28   17   45 
Non-Hispanic or Latino   228   233   461 
Weight [1] 
[Units: Kg]
Mean (Standard Deviation)
 81.15  (14.549)   80.98  (14.296)   81.07  (14.411) 
[1] Data available for 256 and 249 participants in each treatment group respectively
Body Mass Index (BMI) [1] 
[Units: Kg/m²]
Mean (Standard Deviation)
 29.23  (4.406)   29.26  (4.281)   29.25  (4.340) 
[1] Data available for 256 and 249 participants in each treatment group respectively
Fitzpatrick Skin Type [1] 
[Units: Participants]
     
I - III   180   187   367 
IV - VI   76   63   139 
[1]

Fitzpatrick Skin Type is a numerical classification schema for human skin color and typical response to ultraviolet (UV) light:

  • Type I: Pale white skin, blue/hazel eyes, blond/red hair; Always burns, does not tan.
  • Type II: Fair skin, blue eyes; Burns easily, tans poorly.
  • Type III: Darker white skin; Tans after initial burn.
  • Type IV: Light brown skin; Burns minimally, tans easily.
  • Type V: Brown skin; Rarely burns, tans darkly easily.
  • Type VI: Dark brown or black skin; Never burns, always tans darkly.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants Who Achieved a Composite 1-grade Response   [ Time Frame: Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment) ]

2.  Primary:   Percentage of Participants Who Achieved a Composite 2-grade Response   [ Time Frame: Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment) ]

3.  Secondary:   Percentage of Participants With a Magnetic Resonance Imaging (MRI) Response   [ Time Frame: Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment) ]
  Hide Outcome Measure 3

Measure Type Secondary
Measure Title Percentage of Participants With a Magnetic Resonance Imaging (MRI) Response
Measure Description 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.
Time Frame Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT-MRI population consisted of all randomized participants who participated in the MRI cohort and had evaluable Baseline MRI data. A multiple imputation process was used.

Reporting Groups
  Description
Deoxycholic Acid Injection 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.
Placebo Participants received placebo 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.

Measured Values
   Deoxycholic Acid Injection   Placebo 
Participants Analyzed 
[Units: Participants]
 113   111 
Percentage of Participants With a Magnetic Resonance Imaging (MRI) Response 
[Units: Percentage of participants]
 46.3   5.3 


Statistical Analysis 1 for Percentage of Participants With a Magnetic Resonance Imaging (MRI) Response
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Cochran-Mantel-Haenszel
P Value [4] <0.001
Risk Ratio (RR) [5] 8.541
95% Confidence Interval 3.620 to 20.148
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  If both primary endpoints were statistically significant, testing continued to the 2 secondary endpoints using the Bonferroni-Holm method. The smaller of the 2 p-values for the treatment difference was tested at the 0.025 level. If significant, testing proceeded for the remaining secondary endpoint at the 0.05 level. If the smaller p-value was > 0.025, the null hypothesis for the associated variable would not be rejected, and testing of the second endpoint would not proceed.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  CMH method stratified by pooled study center
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  A risk ratio greater than 1 favors deoxycholic acid injection treatment, and between 0 and 1 favors placebo.



4.  Secondary:   Change From Baseline in Patient-Reported Submental Fat Impact Scale (PR-SMFIS)   [ Time Frame: Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Clinical Trial Disclosure
Organization: Kythera
e-mail: clinical_trials@kythera.com



Responsible Party: Kythera Biopharmaceuticals
ClinicalTrials.gov Identifier: NCT01542034     History of Changes
Other Study ID Numbers: ATX-101-11-22
First Submitted: February 24, 2012
First Posted: March 1, 2012
Results First Submitted: May 28, 2015
Results First Posted: June 15, 2015
Last Update Posted: June 15, 2015