Efficacy, Moderate to Severe Convexity of Submental Fat, Safety
Conditions
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.
Interventions
DRUGATX-101
Formulated as an injectable solution containing deoxycholic acid at a concentration of 10 mg/mL.
DRUGPlacebo
Phosphate buffered saline placebo for injection
Sponsors
Kythera Biopharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
65 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
| 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). |
| 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). |
| 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). |
| 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). |
| 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. |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| ATX-101 (Deoxycholic Acid) Injection 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. | 28 |
| 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. | 27 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative decision | 0 | 1 |
| Overall Study | Withdrawal of consent | 3 | 2 |
Baseline characteristics
| Characteristic | ATX-101 (Deoxycholic Acid) Injection | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 68.1 years STANDARD_DEVIATION 2.76 | 67.7 years STANDARD_DEVIATION 2.3 | 67.9 years STANDARD_DEVIATION 2.53 |
| Age, Customized 65-69 years | 22 Participants | 22 Participants | 44 Participants |
| Age, Customized 70-75 years | 6 Participants | 5 Participants | 11 Participants |
| Body Mass Index (BMI) | 29.27 kg/m^2 STANDARD_DEVIATION 4.207 | 30.72 kg/m^2 STANDARD_DEVIATION 4.694 | 29.98 kg/m^2 STANDARD_DEVIATION 4.471 |
| Body mass index category 30 kg/m^2 or greater | 13 Participants | 14 Participants | 27 Participants |
| Body mass index category Less than 30 kg/m^2 | 15 Participants | 13 Participants | 28 Participants |
| Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) score 0 | 0 Participants | 0 Participants | 0 Participants |
| Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) score 1 | 0 Participants | 0 Participants | 0 Participants |
| Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) score 2 | 5 Participants | 6 Participants | 11 Participants |
| Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) score 3 | 23 Participants | 21 Participants | 44 Participants |
| Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) score 4 | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 25 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fitzpatrick Skin Type I | 0 Participants | 1 Participants | 1 Participants |
| Fitzpatrick Skin Type II | 15 Participants | 10 Participants | 25 Participants |
| Fitzpatrick Skin Type III | 7 Participants | 12 Participants | 19 Participants |
| Fitzpatrick Skin Type IV | 2 Participants | 1 Participants | 3 Participants |
| Fitzpatrick Skin Type V | 3 Participants | 2 Participants | 5 Participants |
| Fitzpatrick Skin Type VI | 1 Participants | 1 Participants | 2 Participants |
| Patient-Reported Submental Fat Rating Scale (PR-SMFRS) score 0 | 0 Participants | 0 Participants | 0 Participants |
| Patient-Reported Submental Fat Rating Scale (PR-SMFRS) score 1 | 0 Participants | 0 Participants | 0 Participants |
| Patient-Reported Submental Fat Rating Scale (PR-SMFRS) score 2 | 23 Participants | 19 Participants | 42 Participants |
| Patient-Reported Submental Fat Rating Scale (PR-SMFRS) score 3 | 5 Participants | 8 Participants | 13 Participants |
| Patient-Reported Submental Fat Rating Scale (PR-SMFRS) score 4 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 25 Participants | 25 Participants | 50 Participants |
| Sex: Female, Male Female | 23 Participants | 21 Participants | 44 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
| Submental Skin Laxity Grade (SMSLG) Mild | 8 Participants | 6 Participants | 14 Participants |
| Submental Skin Laxity Grade (SMSLG) Moderate | 20 Participants | 20 Participants | 40 Participants |
| Submental Skin Laxity Grade (SMSLG) None | 0 Participants | 1 Participants | 1 Participants |
| Submental Skin Laxity Grade (SMSLG) Severe | 0 Participants | 0 Participants | 0 Participants |
| Weight | 77.44 kg STANDARD_DEVIATION 14.17 | 84.10 kg STANDARD_DEVIATION 14.07 | 80.71 kg STANDARD_DEVIATION 14.388 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 26 |
| other Total, other adverse events | 28 / 28 | 23 / 26 |
| serious Total, serious adverse events | 0 / 28 | 1 / 26 |
Outcome results
Primary
Change From Baseline in Submental Skin Laxity Grade Scale (SMSLG)
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)
Population: ITT population included all randomized participants, whether or not they received the assigned study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ATX-101 (Deoxycholic Acid) Injection | Change From Baseline in Submental Skin Laxity Grade Scale (SMSLG) | -0.5 scores on a scale | Standard Deviation 0.65 |
| Placebo | Change From Baseline in Submental Skin Laxity Grade Scale (SMSLG) | -0.1 scores on a scale | Standard Deviation 0.45 |
Primary
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
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)
Population: Intent-to treat (ITT) population included all randomized participants, whether or not they received the assigned study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATX-101 (Deoxycholic Acid) Injection | 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 | 68.0 percentage of participants |
| Placebo | 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 | 25.0 percentage of participants |
Primary
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)
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)
Population: ITT population included all randomized participants, whether or not they received the assigned study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATX-101 (Deoxycholic Acid) Injection | 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) | 84.0 percentage of participants |
| Placebo | 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) | 41.7 percentage of participants |
Primary
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)
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)
Population: ITT population included all randomized participants, whether or not they received the assigned study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATX-101 (Deoxycholic Acid) Injection | 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) | 80.0 percentage of participants |
| Placebo | 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) | 45.8 percentage of participants |
Primary
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
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)
Population: ITT population included all randomized participants, whether or not they received the assigned study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATX-101 (Deoxycholic Acid) Injection | 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 | 8.0 percentage of participants |
| Placebo | 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 | 4.2 percentage of participants |
Primary
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)
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)
Population: ITT population included all randomized participants, whether or not they received the assigned study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATX-101 (Deoxycholic Acid) Injection | 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) | 60.0 percentage of participants |
| Placebo | 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) | 12.5 percentage of participants |
Primary
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)
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)
Population: ITT population included all randomized participants, whether or not they received the assigned study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATX-101 (Deoxycholic Acid) Injection | 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) | 20.0 percentage of participants |
| Placebo | 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) | 20.8 percentage of participants |