Moderate or Severe Submental FullnessPhase 3REFINE-1NCT01542034
Phase 3 Study of Deoxycholic Acid Injection (ATX-101) Versus Placebo for the Reduction of Localized Subcutaneous Fat in the Submental Area
A Phase 3 study testing Deoxycholic acid injection in people with Moderate or Severe Submental Fullness, run by Kythera Biopharmaceuticals at 36 sites in 2 countries.
Trial summary
To evaluate the safety and efficacy of deoxycholic acid injection in the reduction of submental fat (fat below the chin). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Moderate or Severe Submental Fullness
- What is being tested?
- Deoxycholic acid injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 506 participants
- Where
- 36 sitesin 2 countries
- Study dates
- Feb 2012to Aug 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Submental fat graded by the investigator as 2 or 3 using the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and graded by the subject as 2 or 3 using the Patient-Reported Submental Fat Rating Scale (PR-SMFRS) as determined on Visit 1 (within 28 days before randomization).
- Dissatisfaction with the submental area expressed by the subject as a rating of 0, 1, or 2 using the Subject Self Rating Scale (SSRS) as determined on Visit 1 (within 28 days before randomization).
- Males and nonpregnant, nonlactating females 18 to 65 years of age, inclusive, on the day of randomization (Visit 2). Females of childbearing potential must have a negative human chorionic gonadotropin (hCG) test result within 28 days before Visit 2 and agree to practice adequate contraception, in the judgment of the investigator, during the course of the study. Females of childbearing potential who are not sexually active need not practice contraception.
- History of stable body weight, in the judgment of the investigator, for at least 6 months before randomization.
- Expected to understand and agree to comply with the visit schedule and all protocol-specified tests and procedures and agreement by the subject to refrain from making significant changes, in the judgment of the investigator, to his or her dietary or exercise habits during the course of the subject's participation.
- Agreement to forego any treatment or behavior (e.g., unshaven facial hair) during the subject's participation in the study that may affect the assessments of the submental area.
- Medically able to undergo the administration of study material determined by clinical and laboratory tests obtained within 28 days before randomization for which the investigator identified no clinically significant abnormality.
- Signed informed consent obtained before any study-specific procedure is performed.
Who cannot join
- History of any intervention to treat submental fat (e.g., liposuction, surgery, or lipolytic agents).
- History of trauma associated with the chin or neck areas that in the judgment of the investigator may affect evaluation of safety or efficacy of treatment.
- A Submental Skin Laxity Grade (SMSLG) of 4 or other anatomical feature (e.g., predominant subplatysmal fat, loose skin in the neck or chin area, prominent platysmal bands), as assessed within 28 days before randomization, for which reduction in submental fat may, in the judgment of the investigator, result in an aesthetically unacceptable outcome.
- Evidence of any cause of enlargement in the submental area (e.g., thyroid enlargement, cervical adenopathy) other than localized submental fat.
- Body mass index of > 40.0 as determined on Visit 1.
- History or current symptoms of dysphagia.
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- A result on coagulation tests (PT, PTT) obtained within 28 days before randomization that indicates the presence of any clinically significant bleeding disorder.
- Any medical condition (e.g., respiratory, cardiovascular, hepatic, neurological disease, or thyroid dysfunction) that would interfere with assessment of safety or efficacy or compromise the subject's ability to undergo study procedures or give informed consent.
- Treatment with radio frequency, laser procedures, chemical peels, or dermal fillers in the neck or chin area within 12 months before randomization.
- Treatment with botulinum toxin injections in the neck or chin area within 6 months before randomization.
- History of sensitivity to any components of the study material
- History of sensitivity to topical or local anesthetics (e.g., lidocaine, benzocaine, procaine).
- Previous randomization in this study or previous participation in a Kythera-sponsored ATX 101 trial.
- Treatment with an investigational device or agent within 30 days before randomization.
- For centers selected to conduct magnetic resonance imaging (MRI) evaluations, any subject with the presence of any condition that would render a subject unsuitable for MRI evaluation (e.g., claustrophobia), or metals in the body that would interfere with MRI acquisition (e.g., nonremovable metal appliances in the mouth such as silver or gold caps, pacemakers, metal joints).
Trial locations and contacts
36 sites in 2 countries.
36 sites in 2 countries
United States31 sites
Investigational Site
Arlington, Illinois, 60005
Investigational Site
Atlanta, Georgia, 30342
Investigational Site
Beverly Hills, California, 90210
Investigational Site
Beverly Hills, California, 90212
Investigational Site
Birmingham, Alabama, 35205
Investigational Site
Charlotte, North Carolina, 28207
Investigational Site
Charlottesville, Virginia, 22911
Investigational Site
Chicago, Illinois, 60611
Investigational Site
Evansville, Indiana, 47713
Investigational Site
Fridley, Minnesota, 55432
Investigational Site
Glenn Dale, Maryland, 20769
Investigational Site
Hunt Valley, Maryland, 21030
Investigational Site
Irvine, California, 92697
Investigational Site
Los Angeles, California, 90201
Investigational Site
Louisville, Kentucky, 40217
Investigational Site
Miami Beach, Florida, 33140
Investigational Site
Nashville, Tennessee, 37203
Investigational Site
Nashville, Tennessee, 37215
Investigational Site
New Haven, Connecticut, 06511
Investigational Site
New York, New York, 10028
Investigational Site
New York, New York, 10029
Investigational Site
Oceanside, California, 92056
Investigational Site
Omaha, Nebraska, 68144
Investigational Site
Rockville, Maryland, 20850
Investigational Site
San Diego, California, 92117
Investigational Site
San Diego, California, 92121
Investigational Site
Snellville, Georgia, 30078
Investigational Site
Spokane, Washington, 99204
Investigational Site
Washington D.C., District of Columbia, 20037
Investigational Site
West Bloomfield, Michigan, 48322
Investigational Site
West Palm Beach, Florida, 33401
Canada5 sites
Investigational Site
Montreal, Quebec, H2K 4L5
Investigational Site
Peterborough, Ontario, K9J 1Z2
Investigational Site
Toronto, Ontario, M5R 3N8
Investigational Site
Toronto, Ontario, M5S 3B4
Investigational Site
Vancouver, B.C., V5Z4E1
About this study
Official title: Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ATX-101 (Sodium Deoxycholate Injection) Versus Placebo for the Reduction of Localized Subcutaneous Fat in the Submental Area
To evaluate the safety and efficacy of deoxycholic acid injection in the reduction of submental fat (fat below the chin).
- Conditions
- Moderate or Severe Submental Fullness
- Being tested
- Deoxycholic acid injection, Placebo
- Medical subject headings
- Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deoxycholic acid injectionDrug
Also called ATX-101, Kybella
Formulated as an injectable solution containing deoxycholic acid at a concentration of 10 mg/mL.
PlaceboDrug
Phosphate buffered saline placebo for injection
| Study group | Role | What they receive |
|---|---|---|
| Deoxycholic Acid Injection | Experimental | 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. Receives: Drug: Deoxycholic acid injection |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Achieved a Composite 1-grade Response
A composite 1-grade response is defined as at least a 1-grade improvement from Baseline on both the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and Patient-Reported Submental Fat Rating Scale (PR-SMFRS) 12 weeks after the last 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.
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.
Measured: Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment)
Percentage of Participants Who Achieved a Composite 2-grade Response
A composite 2-grade response is defined as at least a 2-grade improvement from Baseline on both the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and Patient-Reported Submental Fat Rating Scale (PR-SMFRS) 12 weeks after the last 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.
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.
Measured: Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment)
Secondary outcomes (2)
Percentage of Participants With a Magnetic Resonance Imaging (MRI) Response
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.
Measured: Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment)
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.
Measured: Baseline and 12 weeks after last treatment (up to 32 weeks after first treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2012 (estimated)
- Study startFeb 2012
- Primary completionMay 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Moderate or Severe Submental FullnessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 506 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kythera Biopharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Frederick Beddingfield, MD, PhD, Study director, Kythera Biopharmaceuticals, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01542034
- Sponsor's protocol ID
- ATX-101-11-22
- Acronym
- REFINE-1
- Status last verified
- May 2015
- First submitted
- 24 Feb 2012
- Last updated
- 15 Jun 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ATX-101 (Sodium Deoxycholate Injection) Versus Placebo for the Reduction of Localized Subcutaneous Fat in the Submental Area
- ClinicalTrials.gov ID
- NCT01542034
- Acronym / sponsor ID
- REFINE-1 / ATX-101-11-22
- Conditions
- Moderate or Severe Submental Fullness
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 506 participants (actual)
- Lead sponsor
- Kythera BiopharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Feb 2012
- Primary completion
- May 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 1 Mar 2012 (estimated)
- Results
- Posted 15 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the safety and efficacy of deoxycholic acid injection in the reduction of submental fat (fat below the chin).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Deoxycholic Acid Injection | Experimental | Drug: Deoxycholic acid injectionParticipants 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 | Placebo comparator | Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Submental fat graded by the investigator as 2 or 3 using the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and graded by the subject as 2 or 3 using the Patient-Reported Submental Fat Rating Scale (PR-SMFRS) as determined on Visit 1 (within 28 days before randomization).
- Dissatisfaction with the submental area expressed by the subject as a rating of 0, 1, or 2 using the Subject Self Rating Scale (SSRS) as determined on Visit 1 (within 28 days before randomization).
- Males and nonpregnant, nonlactating females 18 to 65 years of age, inclusive, on the day of randomization (Visit 2). Females of childbearing potential must have a negative human chorionic gonadotropin (hCG) test result within 28 days before Visit 2 and agree to practice adequate contraception, in the judgment of the investigator, during the course of the study. Females of childbearing potential who are not sexually active need not practice contraception.
- History of stable body weight, in the judgment of the investigator, for at least 6 months before randomization.
- Expected to understand and agree to comply with the visit schedule and all protocol-specified tests and procedures and agreement by the subject to refrain from making significant changes, in the judgment of the investigator, to his or her dietary or exercise habits during the course of the subject's participation.
Key exclusion criteria (15 listed)
- History of any intervention to treat submental fat (e.g., liposuction, surgery, or lipolytic agents).
- History of trauma associated with the chin or neck areas that in the judgment of the investigator may affect evaluation of safety or efficacy of treatment.
- A Submental Skin Laxity Grade (SMSLG) of 4 or other anatomical feature (e.g., predominant subplatysmal fat, loose skin in the neck or chin area, prominent platysmal bands), as assessed within 28 days before randomization, for which reduction in submental fat may, in the judgment of the investigator, result in an aesthetically unacceptable outcome.
- Evidence of any cause of enlargement in the submental area (e.g., thyroid enlargement, cervical adenopathy) other than localized submental fat.
- Body mass index of > 40.0 as determined on Visit 1.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Deoxycholic acid injectionAlso: ATX-101, KybellaFormulated as an injectable solution containing deoxycholic acid at a concentration of 10 mg/mL. | Drug | Deoxycholic Acid Injection |
| PlaceboPhosphate buffered saline placebo for injection | Drug | Placebo |
Primary outcome
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)
A composite 1-grade response is defined as at least a 1-grade improvement from Baseline on both the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and Patient-Reported Submental Fat Rating Scale (PR-SMFRS) 12 weeks after the last 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. 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.
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)
A composite 2-grade response is defined as at least a 2-grade improvement from Baseline on both the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and Patient-Reported Submental Fat Rating Scale (PR-SMFRS) 12 weeks after the last 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. 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.
2 secondary outcomes
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Moderate or Severe Submental Fullness
RecruitingPhase 1
A Phase I Study of HY-2003 in the Subjects With Excessive Submental Fat Accumulation
Moderate or Severe Submental Fullness
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frederick Beddingfield, MD, PhD study director
Kythera Biopharmaceuticals, Inc
36 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Deoxycholic acid injection in people with Moderate or Severe Submental Fullness, run by Kythera Biopharmaceuticals at 36 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jun 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2015.