Safety Study of Deoxycholic Acid for the Reduction of Localized Subcutaneous Fat in the Submental Area in Subjects 65 to 75 Years of Age

• Sponsor: Kythera Biopharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02123134
• Collaborator: (none)
• Enrollment: 55
• Locations: 6
• Arms: 2
• Duration (Months): 17
• Patients Per Site: 9.2
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The objectives of this study are to explore the safety and efficacy of subcutaneous injections of Deoxycholic Acid relative to placebo, in the submental area of participants who are 65 to 75 years old.

Condition or Disease	Intervention/Treatment	Phase
Moderate to Severe Convexity of Submental Fat; Safety; Efficacy	Drug: ATX-101; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-blind, Placebo-controlled Safety Study of ATX-101 (Deoxycholic Acid) Injection for the Reduction of Localized Subcutaneous Fat in the Submental Area in Subjects 65 to 75 Years of Age
• Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received placebo administered in 0.2 mL subcutaneous (SC) injections, up to 10 milliliters (mL) per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.	Drug: Placebo; Phosphate buffered saline placebo for injection
Experimental: ATX-101 deoxycholic acid injection Participants received deoxycholic acid 2 mg/cm^2 administered in 0.2 mL SC injections, up to 10 mL per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.	Drug: ATX-101; Formulated as an injectable solution containing deoxycholic acid at a concentration of 10 mg/mL.; Other Names: deoxycholic acid

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With at Least a 1-Grade Reduction (Improvement) at 12 Weeks From Last Treatment Based on Both the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and Patient-Reported Submental Fat Rating Scale (PR-SMFRS) Assessments [Baseline and up to Week 32 (12 weeks after last treatment)]

   The investigator evaluated the participant's chin and neck area using the Clinician-Reported Submental Fat Rating Scale (a 5-point scale) where: 0=absent submental convexity (best) to 4= extreme submental convexity (worst). The participant evaluated their chin and neck area using the Patient-Reported Submental Fat Rating Scale (a 5-point scale) where: 0=no chin fat at all (best) to 4= a very large amount of chin fat (worst).

2. Percentage of Participants With at Least a 2-Grade Reduction (Improvement) at 12 Weeks From Last Treatment Based on Both the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and Patient-Reported Submental Fat Rating Scale (PR-SMFRS) Assessments [Baseline and up to Week 32 (12 weeks after last treatment)]

   The investigator evaluated the participant's chin and neck area using the Clinician-Reported Submental Fat Rating Scale (a 5-point scale) where: 0=absent submental convexity (best) to 4= extreme submental convexity (worst). The participant evaluated their chin and neck area using the Patient-Reported Submental Fat Rating Scale (a 5-point scale) where: 0=no chin fat at all (best) to 4= a very large amount of chin fat (worst).

3. Percentage of Participants With at Least a 1-Grade Reduction (Improvement) at 12 Weeks From Last Treatment Based on the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) [Baseline and up to Week 32 (12 weeks after last treatment)]

   The investigator evaluated the participant's chin and neck area using the CR-SMFRS 5-point scale where: 0=absent submental convexity (best) to 4= extreme submental convexity (worst).

4. Percentage of Participants With at Least a 2-Grade Reduction (Improvement) at 12 Weeks From Last Treatment Based on the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) [Baseline and up to Week 32 (12 weeks after last treatment)]

   The investigator evaluated the participant's chin and neck area using the CR-SMFRS 5-point scale where: 0=absent submental convexity (best) to 4= extreme submental convexity (worst).

5. Percentage of Participants With at Least a 1-Grade Reduction (Improvement) at 12 Weeks From Last Treatment Based on the Patient-Reported Submental Fat Rating Scale (PR-SMFRS) [Baseline and up to Week 32 (12 weeks after last treatment)]

   The participant evaluated their chin and neck area using the PR-SMFRS 5-point scale where: 0=no chin fat at all (best) to 4= a very large amount of chin fat (worst).

6. Percentage of Participants With at Least a 2-Grade Reduction (Improvement) at 12 Weeks From Last Treatment Based on the Patient-Reported Submental Fat Rating Scale (PR-SMFRS) [Baseline and up to Week 32 (12 weeks after last treatment)]

   The participant evaluated their chin and neck area using the PR-SMFRS 5-point scale where: 0=no chin fat at all (best) to 4= a very large amount of chin fat (worst).

7. Change From Baseline in Submental Skin Laxity Grade Scale (SMSLG) [Baseline and up to Week 32 (12 weeks after last treatment)]

   The SMSLG is an integration of three features: skin wrinkling, adherence to underlying neck structures (bone and muscle) and redundancy (horizontal and vertical folds). Each grade (1=none, 2=mild, 3=moderate and 4=severe) defines the maximal allowed limit for skin wrinkling, adherence to underlying structures and redundancy.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Males and females, 65 to 75 years of age

• Stable Body Weight

• Dissatisfaction with the submental area expressed by participants

• Acceptable volume of submental fat graded by clinician

• BMI of ≤40.0 kg/m^2

• Signed informed consent (ICF)

• SMF rating of 2 or 3 by clinician and patient

Exclusion Criteria:

• No prior intervention for submental fat (SMF) (eg liposuction, surgery or lipolytic agents)

• Absence of clinically significant health problems

• Anatomical features for which reduction in SMF may result in aesthetically unacceptable outcome, judged by clinician

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

• Body mass index of ≥40.0 kg/m^2

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States	35205
2		Los Angeles	California	United States	90036
3		Bradenton	Florida	United States	34209
4		Metairie	Louisiana	United States	70006
5		White Plains	New York	United States	10604
6		Cincinnati	Ohio	United States	45255

Sponsors and Collaborators

• Kythera Biopharmaceuticals

Investigators

• Study Director: Frederick Beddingfield, III, MD, PhD, Sponsor GmbH

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kythera Biopharmaceuticals
• ClinicalTrials.gov Identifier: NCT02123134
• Other Study ID Numbers: ATX-101-13-28
• First Posted: Apr 25, 2014
• Last Update Posted: Feb 17, 2020
• Last Verified: Jan 1, 2020

• Additional relevant MeSH terms: Deoxycholic Acid

Study Results

Participant Flow

Recruitment Details	A total of 55 subjects were randomized to either ATX-101 or placebo at a ratio of 1:1. A total of 28 subjects received ATX-101 and 26 subjects received placebo; 1 subject (803-003) was randomized to placebo but was not treated with placebo.

Arm/Group Title	ATX-101 (Deoxycholic Acid) Injection	Placebo
Arm/Group Description	Participants received deoxycholic acid 2 mg/cm^2 administered in 0.2 mL subcutaneous (SC) injections, up to 10 mL per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.	Participants received placebo administered in 0.2 mL subcutaneous (SC) injections, up to 10 milliliters (mL) per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.
Period Title: Overall Study
STARTED	28	27
COMPLETED	25	24
NOT COMPLETED	3	3

Baseline Characteristics

Arm/Group Title	ATX-101 (Deoxycholic Acid) Injection	Placebo	Total
Arm/Group Description	Participants received deoxycholic acid 2 mg/cm^2 administered in 0.2 mL subcutaneous (SC) injections, up to 10 mL per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.	Participants received placebo administered in 0.2 mL subcutaneous (SC) injections, up to 10 milliliters (mL) per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.	Total of all reporting groups
Overall Participants	28	27	55
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.1 (2.76)	67.7 (2.30)	67.9 (2.53)
Age, Customized (Count of Participants)
65-69 years	22 78.6%	22 81.5%	44 80%
70-75 years	6 21.4%	5 18.5%	11 20%
Sex: Female, Male (Count of Participants)
Female	23 82.1%	21 77.8%	44 80%
Male	5 17.9%	6 22.2%	11 20%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.6%	2 7.4%	3 5.5%
Not Hispanic or Latino	27 96.4%	25 92.6%	52 94.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 7.1%	2 7.4%	4 7.3%
White	25 89.3%	25 92.6%	50 90.9%
More than one race	1 3.6%	0 0%	1 1.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Fitzpatrick Skin Type (Count of Participants)
I	0 0%	1 3.7%	1 1.8%
II	15 53.6%	10 37%	25 45.5%
III	7 25%	12 44.4%	19 34.5%
IV	2 7.1%	1 3.7%	3 5.5%
V	3 10.7%	2 7.4%	5 9.1%
VI	1 3.6%	1 3.7%	2 3.6%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	77.44 (14.170)	84.10 (14.070)	80.71 (14.388)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.27 (4.207)	30.72 (4.694)	29.98 (4.471)
Body mass index category (Count of Participants)
Less than 30 kg/m^2	15 53.6%	13 48.1%	28 50.9%
30 kg/m^2 or greater	13 46.4%	14 51.9%	27 49.1%
Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) score (Count of Participants)
0	0 0%	0 0%	0 0%
1	0 0%	0 0%	0 0%
2	5 17.9%	6 22.2%	11 20%
3	23 82.1%	21 77.8%	44 80%
4	0 0%	0 0%	0 0%
Patient-Reported Submental Fat Rating Scale (PR-SMFRS) score (Count of Participants)
0	0 0%	0 0%	0 0%
1	0 0%	0 0%	0 0%
2	23 82.1%	19 70.4%	42 76.4%
3	5 17.9%	8 29.6%	13 23.6%
4	0 0%	0 0%	0 0%
Submental Skin Laxity Grade (SMSLG) (Count of Participants)
None	0 0%	1 3.7%	1 1.8%
Mild	8 28.6%	6 22.2%	14 25.5%
Moderate	20 71.4%	20 74.1%	40 72.7%
Severe	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With at Least a 1-Grade Reduction (Improvement) at 12 Weeks From Last Treatment Based on Both the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and Patient-Reported Submental Fat Rating Scale (PR-SMFRS) Assessments
Description	The investigator evaluated the participant's chin and neck area using the Clinician-Reported Submental Fat Rating Scale (a 5-point scale) where: 0=absent submental convexity (best) to 4= extreme submental convexity (worst). The participant evaluated their chin and neck area using the Patient-Reported Submental Fat Rating Scale (a 5-point scale) where: 0=no chin fat at all (best) to 4= a very large amount of chin fat (worst).
Time Frame	Baseline and up to Week 32 (12 weeks after last treatment)

Outcome Measure Data

Analysis Population Description

Intent-to treat (ITT) population included all randomized participants, whether or not they received the assigned study drug.

Arm/Group Title	ATX-101 (Deoxycholic Acid) Injection	Placebo
Arm/Group Description	Participants received deoxycholic acid 2 mg/cm^2 administered in 0.2 mL subcutaneous (SC) injections, up to 10 mL per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.	Participants received placebo administered in 0.2 mL subcutaneous (SC) injections, up to 10 milliliters (mL) per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.
Measure Participants	25	24
Number (95% Confidence Interval) [percentage of participants]	68.0 242.9%	25.0 92.6%

2. Primary Outcome

Title	Percentage of Participants With at Least a 2-Grade Reduction (Improvement) at 12 Weeks From Last Treatment Based on Both the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and Patient-Reported Submental Fat Rating Scale (PR-SMFRS) Assessments
Description	The investigator evaluated the participant's chin and neck area using the Clinician-Reported Submental Fat Rating Scale (a 5-point scale) where: 0=absent submental convexity (best) to 4= extreme submental convexity (worst). The participant evaluated their chin and neck area using the Patient-Reported Submental Fat Rating Scale (a 5-point scale) where: 0=no chin fat at all (best) to 4= a very large amount of chin fat (worst).
Time Frame	Baseline and up to Week 32 (12 weeks after last treatment)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, whether or not they received the assigned study drug.

Arm/Group Title	ATX-101 (Deoxycholic Acid) Injection	Placebo
Arm/Group Description	Participants received deoxycholic acid 2 mg/cm^2 administered in 0.2 mL subcutaneous (SC) injections, up to 10 mL per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.	Participants received placebo administered in 0.2 mL subcutaneous (SC) injections, up to 10 milliliters (mL) per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.
Measure Participants	25	24
Number (95% Confidence Interval) [percentage of participants]	8.0 28.6%	4.2 15.6%

3. Primary Outcome

Title	Percentage of Participants With at Least a 1-Grade Reduction (Improvement) at 12 Weeks From Last Treatment Based on the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS)
Description	The investigator evaluated the participant's chin and neck area using the CR-SMFRS 5-point scale where: 0=absent submental convexity (best) to 4= extreme submental convexity (worst).
Time Frame	Baseline and up to Week 32 (12 weeks after last treatment)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, whether or not they received the assigned study drug.

Arm/Group Title	ATX-101 (Deoxycholic Acid) Injection	Placebo
Arm/Group Description	Participants received deoxycholic acid 2 mg/cm^2 administered in 0.2 mL subcutaneous (SC) injections, up to 10 mL per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.	Participants received placebo administered in 0.2 mL subcutaneous (SC) injections, up to 10 milliliters (mL) per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.
Measure Participants	25	24
Number (95% Confidence Interval) [percentage of participants]	84.0 300%	41.7 154.4%

4. Primary Outcome

Title	Percentage of Participants With at Least a 2-Grade Reduction (Improvement) at 12 Weeks From Last Treatment Based on the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS)
Description	The investigator evaluated the participant's chin and neck area using the CR-SMFRS 5-point scale where: 0=absent submental convexity (best) to 4= extreme submental convexity (worst).
Time Frame	Baseline and up to Week 32 (12 weeks after last treatment)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, whether or not they received the assigned study drug.

Arm/Group Title	ATX-101 (Deoxycholic Acid) Injection	Placebo
Arm/Group Description	Participants received deoxycholic acid 2 mg/cm^2 administered in 0.2 mL subcutaneous (SC) injections, up to 10 mL per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.	Participants received placebo administered in 0.2 mL subcutaneous (SC) injections, up to 10 milliliters (mL) per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.
Measure Participants	25	24
Number (95% Confidence Interval) [percentage of participants]	60.0 214.3%	12.5 46.3%

5. Primary Outcome

Title	Percentage of Participants With at Least a 1-Grade Reduction (Improvement) at 12 Weeks From Last Treatment Based on the Patient-Reported Submental Fat Rating Scale (PR-SMFRS)
Description	The participant evaluated their chin and neck area using the PR-SMFRS 5-point scale where: 0=no chin fat at all (best) to 4= a very large amount of chin fat (worst).
Time Frame	Baseline and up to Week 32 (12 weeks after last treatment)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, whether or not they received the assigned study drug.

Arm/Group Title	ATX-101 (Deoxycholic Acid) Injection	Placebo
Arm/Group Description	Participants received deoxycholic acid 2 mg/cm^2 administered in 0.2 mL subcutaneous (SC) injections, up to 10 mL per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.	Participants received placebo administered in 0.2 mL subcutaneous (SC) injections, up to 10 milliliters (mL) per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.
Measure Participants	25	24
Number (95% Confidence Interval) [percentage of participants]	80.0 285.7%	45.8 169.6%

6. Primary Outcome

Title	Percentage of Participants With at Least a 2-Grade Reduction (Improvement) at 12 Weeks From Last Treatment Based on the Patient-Reported Submental Fat Rating Scale (PR-SMFRS)
Description	The participant evaluated their chin and neck area using the PR-SMFRS 5-point scale where: 0=no chin fat at all (best) to 4= a very large amount of chin fat (worst).
Time Frame	Baseline and up to Week 32 (12 weeks after last treatment)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, whether or not they received the assigned study drug.

Arm/Group Title	ATX-101 (Deoxycholic Acid) Injection	Placebo
Arm/Group Description	Participants received deoxycholic acid 2 mg/cm^2 administered in 0.2 mL subcutaneous (SC) injections, up to 10 mL per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.	Participants received placebo administered in 0.2 mL subcutaneous (SC) injections, up to 10 milliliters (mL) per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.
Measure Participants	25	24
Number (95% Confidence Interval) [percentage of participants]	20.0 71.4%	20.8 77%

7. Primary Outcome

Title	Change From Baseline in Submental Skin Laxity Grade Scale (SMSLG)
Description	The SMSLG is an integration of three features: skin wrinkling, adherence to underlying neck structures (bone and muscle) and redundancy (horizontal and vertical folds). Each grade (1=none, 2=mild, 3=moderate and 4=severe) defines the maximal allowed limit for skin wrinkling, adherence to underlying structures and redundancy.
Time Frame	Baseline and up to Week 32 (12 weeks after last treatment)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, whether or not they received the assigned study drug.

Arm/Group Title	ATX-101 (Deoxycholic Acid) Injection	Placebo
Arm/Group Description	Participants received deoxycholic acid 2 mg/cm^2 administered in 0.2 mL subcutaneous (SC) injections, up to 10 mL per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.	Participants received placebo administered in 0.2 mL subcutaneous (SC) injections, up to 10 milliliters (mL) per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.
Measure Participants	25	24
Mean (Standard Deviation) [scores on a scale]	-0.5 (0.65)	-0.1 (0.45)

Adverse Events

Time Frame	Up to 32 Weeks
Adverse Event Reporting Description	Safety population included all randomized participants who received at least 1 injection of study drug.
Arm/Group Title	ATX-101 (Deoxycholic Acid) Injection		Placebo
Arm/Group Description	Participants received deoxycholic acid 2 mg/cm^2 administered in 0.2 mL subcutaneous (SC) injections, up to 10 mL per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.		Participants received placebo administered in 0.2 mL subcutaneous (SC) injections, up to 10 milliliters (mL) per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments.
All Cause Mortality
	ATX-101 (Deoxycholic Acid) Injection		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/26 (0%)
Serious Adverse Events
	ATX-101 (Deoxycholic Acid) Injection		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		1/26 (3.8%)
Infections and infestations
Urosepsis	0/28 (0%)	0	1/26 (3.8%)	1
Other (Not Including Serious) Adverse Events
	ATX-101 (Deoxycholic Acid) Injection		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/28 (100%)		23/26 (88.5%)
General disorders
Injection site bruising	20/28 (71.4%)	42	15/26 (57.7%)	35
Injection site pain	20/28 (71.4%)	44	3/26 (11.5%)	6
Injection site swelling	17/28 (60.7%)	38	15/26 (57.7%)	54
Injection site anaesthesia	14/28 (50%)	16	0/26 (0%)	0
Injection site nodule	8/28 (28.6%)	8	3/26 (11.5%)	3
Injection site oedema	5/28 (17.9%)	14	0/26 (0%)	0
Injection site erythema	4/28 (14.3%)	9	3/26 (11.5%)	4
Injection site induration	4/28 (14.3%)	7	0/26 (0%)	0
Infections and infestations
Nasopharyngitis	0/28 (0%)	0	2/26 (7.7%)	2
Musculoskeletal and connective tissue disorders
Pain in jaw	2/28 (7.1%)	2	0/26 (0%)	0
Nervous system disorders
Headache	1/28 (3.6%)	1	2/26 (7.7%)	2
Respiratory, thoracic and mediastinal disorders
Dysphonia	2/28 (7.1%)	2	0/26 (0%)	0
Skin and subcutaneous tissue disorders
Skin tightness	2/28 (7.1%)	2	1/26 (3.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A 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 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.