Submental Study (Sequential Treatment Approach)

Study Overview
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Brief Summary
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Evaluate the safety and efficacy of subcutaneous fat layer reduction in the submental area using multiple therapeutic tools.

Detailed Description
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The Zeltiq CoolSculpting System and the sequential use of the injectable drug Kybella for non-invasive and then minimally invasive fat reduction in the submental area will be evaluated during the study.

Official Title
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Fat Reduction in the Submental Area - a Sequential Treatment Approach With CoolMini and KYBELLA®

Conditions
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Body Fat Disorder

Intervention / Treatment
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* Device: The ZELTIQ CoolSculpting System
* Drug: Kybella 20 MG in 2 ML Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Male or female subjects > 22 years of age and < 65 years of age. Women of childbearing potential must have a negative urine pregnancy test result at screening and agree to practice adequate contraception. CR-SMFRS grade of 4 (extreme) as determined by the evaluating investigator at screening. 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 at Screening visit. History of stable body weight confirmed by the subject, for at least 6 months prior to the first treatment session. Subject agrees to maintain his/her weight (i.e., within 5%) by not making any major changes in their diet or exercise routine during the course of the study. Subject agrees to forgo 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. Subject is medically able to undergo the administration of KYBELLA® determined after review of the subject's medical history for which the evaluating investigator identifies no clinically significant abnormality. Subject has read and signed the study written informed consent form. Exclusion Criteria Body Mass Index ≥40 as determined at screening. Subject has excessive skin laxity, as determined by the evaluating investigator, in the neck or chin area or other anatomical feature (e.g., predominant subplatysmal fat, loose skin in the neck or chin area, prominent platysmal bands) for which reduction in the submental fat may result in an aesthetically unacceptable outcome. There is evidence of any cause of enlargement in the submental area (e.g., thyroid enlargement, cervical adenopathy) other than localized submental fat. Subject has a history of trauma associated with the chin or neck areas, which in the judgement of the investigator may affect evaluation of safety or efficacy of treatment. Subject has a history of treatment with CoolSculpting or KYBELLA® in the intended treatment area or has a history of any intervention to treat submental fat (e.g., liposuction, surgery, or lipolytic agents). Subject has a history of treatment with radiofrequency, micro-focused ultrasound, laser procedures, chemical peels, or dermal fillers in the neck or chin area within 12 months before the first treatment session. Subject has a history of treatment with botulinum toxin injections in the neck or chin area within 6 months before the first treatment session. Subject has a known history of cryoglobulinemia, cold urticaria, paroxysmal cold hemoglobinuria or cold agglutinin disease. Subject has a known history of Raynaud's disease, or any known condition with a response to cold exposure that limits blood flow to the skin. Subject has a history of facial nerve paresis or paralysis (such as Bell's palsy) Subject has a history or current symptoms of dysphagia. Subject has a history of prior neck surgery, or prior surgery in the area of intended treatment, or implant in or adjacent to the area of intended treatment. Subject has a history of sensitivity to any components of the KYBELLA® or to topical or local anesthetics (e.g., lidocaine, benzocaine, novocaine). Subject has a history of bleeding disorder or is taking any medication that in the investigator's opinion may increase the subject's risk of bruising. Subject is currently taking or has taken diet pills or weight control supplements within the past month. Subject has any dermatological conditions, such as scars in the location of the treatment area that may interfere with the treatment or evaluation. Subject has an active implanted device such as a pacemaker, defibrillator, or drug delivery system. Women of childbearing potential not using a reliable means of contraception. Subject is unable or unwilling to comply with the study requirements. Subject has received treatment with an investigational device or agent within 30 days before the subject's first treatment session. Any other condition or laboratory value that would, in the professional opinion of the investigator, potentially affect the subject's response or the integrity of the data or would pose an unacceptable risk to the subject.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Kybella and Zeltiq CoolSculpting CoolMini
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment for Submental Fat Reduction withCoolSculpting System followed by Kybella<br>CoolSculpting followed by Kybella treatments. Kybella supplied in 2mL vials. | Device: The ZELTIQ CoolSculpting System<br>* The CoolSculpting machine will be used to perform the treatments.<br>Drug: Kybella 20 MG in 2 ML Injection<br>* Injectable drug called KYBELLA® (deoxycholic acid)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Subjects Who Have at Least a 1-grade Improvement on the Clinician Reported Submental Fat Rating Scale (CR-SMFRS) at the Final Follow-up Visit When Compared to the Baseline Grade. | The CR-SMFRS is a 5-point scale ranging from 0 to 5, with '0' = Absent Submental Convexity: no localized submental fat evident, '1' = Mild Submental Convexity: minimal localized submental fat, '2'= Moderate Submental Convexity: prominent, localized submental fat, '3' = Severe Submental Convexity: Marked, localized submental fat, '4' = Extreme Submental Convexity. The investigator performed the evaluation of each subject, including palpation of the neck and chin area; oblique anterior and profile views of the chin and neck; and observation of pronation, supination and lateral movement of the head. The score was determined during a live assessment while the subject's head was in the Frankfort plane posture and was recorded as a whole number. | Baseline and 12-week post-treatment follow-up visit. | 
| The Proportion of Subjects for Whom a 2-grade Improvement Was Recorded Using the CR-SMFRS From Baseline to Final Follow-uo Visit. | The CR-SMFRS is a 5-point scale ranging from 0 to 5, with '0' = Absent Submental Convexity: no localized submental fat evident, '1' = Mild Submental Convexity: minimal localized submental fat, '2'= Moderate Submental Convexity: prominent, localized submental fat, '3' = Severe Submental Convexity: Marked, localized submental fat, '4' = Extreme Submental Convexity. The investigator performed the evaluation of each subject, including palpation of the neck and chin area; oblique anterior and profile views of the chin and neck; and observation of pronation, supination and lateral movement of the head. The score was determined during a live assessment while the subject's head was in the Frankfort plane posture and was recorded as a whole number. | Baseline and 12-week post-treatment follow-up visit. | 
| The Number of Device, Drug or Procedure-related Adverse Events. | Adverse event information is collected from the time of study enrollment to the completion of the final follow-up visit. Investigators determined if adverse events occurring in the study are 'Not Related', 'Possibly Related', 'Probably Related', or have a 'Causal relationship to the study device, drug or procedure. | 12-week post-treatment follow-up visit, approximately 31 weeks from enrollment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Submental Fat Layer Thickness as Measured by Ultrasound. | Change in the fat layer thickness will be calculated by comparison of pre-treatment and 12 week post-final treatment ultrasound measurements taken in the area treated with the device. The Sponsor's standardized techniques for obtaining ultrasound imaging will be used. Overall fat layer thickness changes will be normalized for each subject by subtracting the change in the pre-treatment area from the change in treated area to remove the influence of weight variations. This result is considered the treatment effect. Results indicate the fat layer reduction in centimeters. | 12-week post-treatment follow-up visit. | 
| Subject Satisfaction as Measured by a Comparison of Baseline and 12-weeks Post-final Treatment of Completed Subject Self-Rating Scales (SSRS). | The SSRS is a 7-point scale with 0 = extremely dissatisfied 1= dissatisfied, 2 = slightly dissatisfied, 3 = neither satisfied nor dissatisfied, 4 = slightly dissatisfied, 5 = satisfied, and 6 = extremely satisfied. The percentage of subjects reporting slightly satisfied, satisfied or extremely satisfied is presented. | Baseline and 12-weeks post- final treatment visit. |