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

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Consent Withdrawn (Subject Convenience)	20	12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)
Body Mass Index (BMI) [1]; [Units: Kg/m²]; Mean (Standard Deviation)	29.23 (4.406)	29.26 (4.281)	29.25 (4.340)
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

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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) ]

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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) ]

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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) ]

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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	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) ]

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  Serious Adverse Events

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  Other Adverse Events

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  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
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  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: 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. 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. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.; Restriction Description: The Clinical Study Agreement requires that the investigator or institution obtain written consent from Kythera prior to presenting and/or publishing results of this study.

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