Moderate or Severe Submental Fullness
Conditions
Brief summary
Evaluation of the safety, tolerability and efficacy of deoxycholic acid injection in the reduction of submental fat (fat below the chin).
Interventions
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
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Moderate or severe submental fat * Dissatisfaction with submental area * History of stable body weight * Signed informed consent
Exclusion criteria
* Any medical or other condition that would affect subject safety or evaluation of efficacy * Previous intervention in the submental area
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Clinician-Reported Submental Fat Rating Scale Scores | Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment) | 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 (0-4) with 0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = extreme. A negative change from Baseline indicates improvement. |
| Change From Baseline in Patient-Reported Submental Fat Scale Rating Scale (PR-SMFRS) | Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment) | The PR-SMFRS is based on the participant's response to the question How much fat do you have under your chin right now? answered on a 5-point ordinal scale (0-4) with 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. |
| Change From Baseline in Patient-Reported Submental Fat Impact Scale (PR-SMFIS) | Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment) | The PR-SMFIS assesses the impact of submental fat on self-perception of 6 emotional and visual characteristics related to the appearance of submental fullness (unhappy, bothered, self-conscious, embarrassed, look older, and look overweight) 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Submental Fat Volume | Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment) | Submental fat volume was measured by magnetic resonance imaging (MRI). |
| Change From Baseline in Submental Fat Thickness | Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment) | Submental fat thickness was measured by magnetic resonance imaging (MRI). |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 10 centers in the United States.
Participants by arm
| Arm | Count |
|---|---|
| Deoxycholic Acid Injection 1 mg/cm² Participants received deoxycholic acid 1 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. | 41 |
| Deoxycholic Acid Injection 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. | 43 |
| 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. | 45 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 0 |
| Overall Study | Lack of Submental Fat | 2 | 8 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 |
| Overall Study | Miscellaneous Reasons | 2 | 1 | 1 |
| Overall Study | Patient Request | 0 | 1 | 0 |
| Overall Study | Withdrawal of Consent | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | Deoxycholic Acid Injection 1 mg/cm² | Total | Placebo | Deoxycholic Acid Injection 2 mg/cm² |
|---|---|---|---|---|
| Age, Continuous | 45.3 years STANDARD_DEVIATION 9.57 | 46.1 years STANDARD_DEVIATION 9.72 | 47.4 years STANDARD_DEVIATION 10.2 | 45.6 years STANDARD_DEVIATION 9.43 |
| Body Mass Index (BMI) | 29.68 kg/m² STANDARD_DEVIATION 4.845 | 30.70 kg/m² STANDARD_DEVIATION 5.665 | 30.85 kg/m² STANDARD_DEVIATION 5.315 | 31.48 kg/m² STANDARD_DEVIATION 6.633 |
| Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) Rating 2 | 17 participants | 57 participants | 18 participants | 22 participants |
| Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) Rating 3 | 24 participants | 72 participants | 27 participants | 21 participants |
| Fitzpatrick Skin Type I - III | 30 participants | 89 participants | 33 participants | 26 participants |
| Fitzpatrick Skin Type IV - VI | 11 participants | 40 participants | 12 participants | 17 participants |
| Race/Ethnicity, Customized Asian | 1 participants | 3 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized Black or African American | 3 participants | 7 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 participants | 11 participants | 4 participants | 6 participants |
| Race/Ethnicity, Customized Other | 1 participants | 3 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 38 participants | 109 participants | 36 participants | 35 participants |
| Sex: Female, Male Female | 29 Participants | 92 Participants | 31 Participants | 32 Participants |
| Sex: Female, Male Male | 12 Participants | 37 Participants | 14 Participants | 11 Participants |
| Weight | 84.88 kg STANDARD_DEVIATION 15.835 | 87.39 kg STANDARD_DEVIATION 17.851 | 87.78 kg STANDARD_DEVIATION 16.059 | 89.32 kg STANDARD_DEVIATION 21.225 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 40 / 41 | 40 / 43 | 43 / 45 |
| serious Total, serious adverse events | 0 / 41 | 1 / 43 | 0 / 45 |
Outcome results
Primary
Change From Baseline in Clinician-Reported Submental Fat Rating Scale Scores
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 (0-4) with 0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = extreme. A negative change from Baseline indicates improvement.
Time frame: Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment)
Population: Modified Intent-to-Treat (mITT) population including all randomized participants who received at least 1 injection of study drug and had at least 1 post-baseline observation for CR-SMFRS, Subject Self-Rating Scale (SSRS), or magnetic resonance imaging (MRI) volume. Last observation carried forward (LOCF) method was used to impute missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Deoxycholic Acid Injection 1 mg/cm² | Change From Baseline in Clinician-Reported Submental Fat Rating Scale Scores | -0.7 units on a scale |
| Deoxycholic Acid Injection 2 mg/cm² | Change From Baseline in Clinician-Reported Submental Fat Rating Scale Scores | -0.8 units on a scale |
| Placebo | Change From Baseline in Clinician-Reported Submental Fat Rating Scale Scores | -0.4 units on a scale |
Comparison: There was no formal hypothesis testing and no adjustments for multiple comparisons.p-value: 0.05295% CI: [-0.61, 0]ANCOVA
Comparison: There was no formal hypothesis testing and no adjustments for multiple comparisons.p-value: 0.00395% CI: [-0.77, -0.16]ANCOVA
Primary
Change From Baseline in Patient-Reported Submental Fat Impact Scale (PR-SMFIS)
The PR-SMFIS assesses the impact of submental fat on self-perception of 6 emotional and visual characteristics related to the appearance of submental fullness (unhappy, bothered, self-conscious, embarrassed, look older, and look overweight) 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.
Time frame: Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment)
Population: Modified intent-to-treat population with available Baseline data; LOCF method was used to impute missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Deoxycholic Acid Injection 1 mg/cm² | Change From Baseline in Patient-Reported Submental Fat Impact Scale (PR-SMFIS) | -3.5 units on a scale |
| Deoxycholic Acid Injection 2 mg/cm² | Change From Baseline in Patient-Reported Submental Fat Impact Scale (PR-SMFIS) | -4.5 units on a scale |
| Placebo | Change From Baseline in Patient-Reported Submental Fat Impact Scale (PR-SMFIS) | -2.1 units on a scale |
Comparison: There was no formal hypothesis testing and no adjustments for multiple comparisons.p-value: 0.00595% CI: [-2.44, -0.46]ANCOVA
Comparison: There was no formal hypothesis testing and no adjustments for multiple comparisons.p-value: <0.00195% CI: [-3.48, -1.48]ANCOVA
Primary
Change From Baseline in Patient-Reported Submental Fat Scale Rating Scale (PR-SMFRS)
The PR-SMFRS is based on the participant's response to the question How much fat do you have under your chin right now? answered on a 5-point ordinal scale (0-4) with 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.
Time frame: Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment)
Population: Modified intent-to-treat population with available Baseline data; LOCF method was used to impute missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Deoxycholic Acid Injection 1 mg/cm² | Change From Baseline in Patient-Reported Submental Fat Scale Rating Scale (PR-SMFRS) | -0.9 units on a scale |
| Deoxycholic Acid Injection 2 mg/cm² | Change From Baseline in Patient-Reported Submental Fat Scale Rating Scale (PR-SMFRS) | -1.3 units on a scale |
| Placebo | Change From Baseline in Patient-Reported Submental Fat Scale Rating Scale (PR-SMFRS) | -0.7 units on a scale |
Comparison: There was no formal hypothesis testing and no adjustments for multiple comparisons.p-value: 0.11795% CI: [-0.55, 0.06]ANCOVA
Comparison: There was no formal hypothesis testing and no adjustments for multiple comparisons.p-value: <0.00195% CI: [-0.91, -0.3]ANCOVA
Secondary
Change From Baseline in Submental Fat Thickness
Submental fat thickness was measured by magnetic resonance imaging (MRI).
Time frame: Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment)
Population: Modified intent-to-treat population; LOCF method was used to impute missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Deoxycholic Acid Injection 1 mg/cm² | Change From Baseline in Submental Fat Thickness | -1.8 mm |
| Deoxycholic Acid Injection 2 mg/cm² | Change From Baseline in Submental Fat Thickness | -1.9 mm |
| Placebo | Change From Baseline in Submental Fat Thickness | -0.3 mm |
p-value: <0.00195% CI: [-2.32, -0.69]ANCOVA
p-value: <0.00195% CI: [-2.46, -0.85]ANCOVA
Secondary
Change From Baseline in Submental Fat Volume
Submental fat volume was measured by magnetic resonance imaging (MRI).
Time frame: Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment)
Population: Modified intent-to-treat population; LOCF method was used to impute missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Deoxycholic Acid Injection 1 mg/cm² | Change From Baseline in Submental Fat Volume | -614 mm³ |
| Deoxycholic Acid Injection 2 mg/cm² | Change From Baseline in Submental Fat Volume | -118 mm³ |
| Placebo | Change From Baseline in Submental Fat Volume | -8.1 mm³ |
p-value: 0.16695% CI: [-1482, 269.3]ANCOVA
p-value: 0.80395% CI: [-1013, 792.6]ANCOVA