Evaluate the Efficacy and Safety of Polyene Phosphatidylcholine Injection (AYP-101) for the Reduction of Submental Fat

Study Overview
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Brief Summary
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Phase 2 trial to evaluate the safety and potential efficacy of three concentration of polyene phosphatidylcholine injection (AYP-101) compared to placebo for the reduction of submental fat.

Detailed Description
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This study is to determine the optimal dose and evaluate safety and efficacy of Polyene Phosphatidylcholine S.C injection (AYP-101) for the reduction of Submental Fat (SMF) who wish improvement in the appearance of moderate to severe convexity or fullness associated with SMF in adults.

Official Title
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A Multicenter, Randomized, Subject-assessor Blind, Placebo Controlled Phase Ⅱ Study to Determine the Optimal Dose of AYP-101 S.C. Injection for the Reduction of Submental Fat

Conditions
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Moderate or Severe Submental Fullness

Intervention / Treatment
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* Drug: Polyene phosphatidylcholine injection
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female over 19 and under 65 years old. 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. 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. Stable weight over the last 6 months (body weight change within +/- 5kg), subject who should refrain from exercise and diet that may affect the study results, and who agreed to remain it for the study period. Signed informed consent obtained before any study-specific procedure is performed. Exclusion Criteria: Allergic to beans or medical devices which used in this clinical trial (sterile oil pan, alcohol swab, grid pad, needle, etc.). Hypersensitivity to the components of the clinical drug, lidocaine or acetaminophen. Central, endocrine, or hereditary obesity (BMI 35kg/m2 or more). Unable to undergo MRI by neurosis or general weakness. History of any treatment (orthognathic surgery, suction lipectomy, Polyene Phosphatidylcholine (PPC) injection) in the neck or chin area. History of any treatment such as massotherapy, carboxy, laser surgery, acupuncture needle, filler, chemical peeling, a botox surgery within 1 year before screening. Inflammation, scars or surgery on the injection area. Judged to be unsuitable subject for the clinical trials; ① Abnormal or sagging skin, ② Noticeable platysma band under the chin area, ③ Less or short chin than normal. Chin or neck disease that are considered to have an impact on the clinical trial such as lymphadenopathy. History of or present symptoms of dysphagia. Heart disease (cardiac insufficiency, angina, cardiac infarction) or stroke within 6 months before screening. Requiring treatment of joint inflammation or a lung disease. Uncontrolled hypertension (systolic blood pressure greater than 180 mmHg or diastolic blood pressure greater than 110 mmHg) or type 2 diabetes mellitus (HbA1c> 9%). Type 1 diabetes mellitus who needs insulin treatment. Autoimmune disorder as well as those who takes immunodepressant drugs. Hemostatic disorder or those who takes anticoagulant drug such as warfarin and clopidogrel. Thyromegaly, thyrotoxicosis, or HIV-positive. Diagnosed with malignant tumor within the last 5 years. Severe renal dysfunction (serum creatinine > 2.0 mg/dl) or severe dyshepatia (ALT, aspartate aminotransferase(AST), alkaline phosphatase > maximum rate of normality x 2.5). History of serious psychiatric disease (Depression, schizophrenia, epilepsy, alcoholism, drug addiction, anorexia, anorexia nervosa, etc.). History of taken a drug that can affect body weight or lipid metabolism such as anorectic agent, steroids, thyroid hormones, amphetamine, cyproheptadine, phenothiazine, or drugs that affect absorption, metabolism, and excretion within 3 months before screening. History of other clinical trial studies within 3 months before screening. Women who are pregnant, breastfeeding, having pregnancy plan, or did not agreed to the contraception (contraceptive pills, contraceptive hormones, intrauterine contraceptive device, spermicide, condoms etc.). Judged to be unsuitable subject for the clinical trials. No or unable to using Smart phone to fill in the e-Pro. Artificial or cavity teeth filled with metallic material (iron, gold, amalgam, cobalt, titanium) which makes misinterpret MRI.

Ages Eligible for Study
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Minimum Age: 19 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2.5% Polyene Phosphatidylcholine Injection 0.2 mL/1.0 cm<br>Participants receive 2.5% polyene phosphatidylcholine administered in 0.2 mL injections, 1.0 cm apart, up to 10.0 ml per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments. | Drug: Polyene phosphatidylcholine injection<br>* Formulated as an injectable solution containing Polyene Phosphatidylcholine at two concentration of 25 mg/mL and 50 mg/mL.<br>* Other names: AYP-101;|
| Experimental: 5.0% Polyene Phosphatidylcholine Injection 0.2 mL/1.0 cm<br>Participants receive 5.0% polyene phosphatidylcholine administered in 0.2 mL injections, 1.0 cm apart, up to 10.0 ml per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments. | Drug: Polyene phosphatidylcholine injection<br>* Formulated as an injectable solution containing Polyene Phosphatidylcholine at two concentration of 25 mg/mL and 50 mg/mL.<br>* Other names: AYP-101;|
| Experimental: 5.0% Polyene Phosphatidylcholine Injection 0.4 mL/1.0 cm<br>Participants receive 5.0% polyene phosphatidylcholine administered in 0.4 mL injections, 1.0 cm apart, up to 20.0 ml per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments. | Drug: Polyene phosphatidylcholine injection<br>* Formulated as an injectable solution containing Polyene Phosphatidylcholine at two concentration of 25 mg/mL and 50 mg/mL.<br>* Other names: AYP-101;|
| Placebo Comparator: Placebo 0.2 mL/1.0 cm<br>Participants receive placebo administered in 0.2 mL injections, 1.0 cm apart, up to 10.0 ml per treatment session at intervals of approximately 1 month for up to a maximum of 6 treatments. | Drug: Placebo<br>* Phosphate buffered saline placebo for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved a Composite 1-grade Response with Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and Patient-Reported Submental Fat Rating Scale (PR-SMFRS) Compared to the Baseline | 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) is evaluated by independent assessor and Patient-Reported Submental Fat Rating Scale (PR-SMFRS) using the following scale: 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. | Baseline and 12 weeks after last treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved a Composite 1-grade Response with Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) Compared to the Baseline | The CR-SMFRS is defined as at least a 1-grade improvement is evaluated by independent assessor from Baseline using the following scale: 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. | Baseline and 12 weeks after last treatment | 
| Percentage of Participants Who Achieved a Composite 1-grade Response with Patient-Reported Submental Fat Rating Scale (PR-SMFRS) Compared to the Baseline | 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): 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. | Baseline and 12 weeks after last treatment | 
| Change From Baseline in a Magnetic Resonance Imaging (MRI) Response in Pre-platysmal Area | Change rate of reduction in pre-platysmal volume. | Baseline and 12 weeks after last treatment | 
| Change From Baseline in a Magnetic Resonance Imaging (MRI) Response in Platysmal Area | Change rate of reduction in platysmal volume. | Baseline and 12 weeks after last treatment | 
| Percentage of Participants Who Achieved a Composite 2-grade Response with Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and Patient-Reported Submental Fat Rating Scale (PR-SMFRS) Compared to the Baseline | 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) is evaluated by independent assessor and Patient-Reported Submental Fat Rating Scale (PR-SMFRS) using the following scale: 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. | Baseline and 12 weeks after last treatment | 
| Change From Baseline in Participants With a Subject Self Rating Scale (SSRS) Response | A SSRS response is defined as an SSRS score that is 4 or greater 12 weeks after the last treatment. The SSRS assesses participant's satisfaction with their appearance in association with the face and chin on a 7-point scale from 0 to 6: where 0 = Extremely dissatisfied, 1 = Dissatisfied, 2 = Slightly dissatisfied, 3 = Neither satisfied nor dissatisfied, 4 = Slightly satisfied, 5 = Satisfied and 6 = Extremely satisfied. | Baseline and 12 weeks after last treatment | 
| Change From Baseline in Patient-Reported Submental Fat Impact Scale (PR-SMFIS) | Patients are asked to rate the visual and emotional impact that the appearance of submental fullness had on their self-perception using 11-point scale range from 0 (no impact) to 10 (extreme impact). | Baseline and 12 weeks after last treatment | 
| Change From Baseline in Depth of Cervical Mental Angle Analyzed with 3D Scanner | The cervical mental angle is measured using a 3D scanner photograph obtained at first and last visit. | Baseline and 12 weeks after last treatment | 
| Patient Global Impression of Change scale (PGIC) | Patient global impression of change scale (PGIC) is to rate patients total improvement or worsening in the appearance since before the first treatment compared to final treatment with 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse. | 12 weeks after last treatment | 
| Change From Baseline in Derriford Appearance Scale 24 (DAS24) | Difference of Derriford Appearance Scale 24 (DAS24) is to measure distress and dysfunction to problems of appearance with 24 questions using 4-point from 0 (None) to 4 (more distress). | Baseline and 12 weeks after last treatment | 
| Change From Baseline in Body Image Quality of Life Inventory (BIQLI) | Body Image Quality Life Inventory (BIQLI) assesses participants' body image using 7-point ranging from -3 (very negative) to +3 (very positive). | Baseline and 12 weeks after last treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Apoptosis, Lipolysis, Fat reduction, Submental fat, Polyene Phosphatidylcholine