Evaluation the Effects of Various Treatments on RZL-012-Induced Adverse Events

Study Overview
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Brief Summary
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This is a Phase 2, open-label, 2-stage, adaptive-design study in which subjects will be randomized into one of 5 treatment groups comprised of RZL-012 with or without additional study treatments:

Detailed Description
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In the first stage of the study, 5 subjects will be randomized into each of the treatment groups. Study outcomes will be assessed up to one week thereafter to determine the need to modify additional study treatments. Subsequently up to 10 additional subjects will be randomized into each of the treatment groups for the second stage of the study. For each subject, the study will consist of a screening period, baseline period in which subjects will receive a single treatment session of RZL-012 and a follow-up period. RZL-012 will be administered during a single treatment session via multiple injections into the submental area under the chin. Subjects will thereafter be monitored for safety and efficacy for at least 84 days. Each subject will be treated with the same dose of RZL-012 : • RZL-012 (concentration of injected solution 50 mg/mL RZL-012) of 7.5 mg/0.15 mL/injection point that results in a total dose/volume of 240±30mg mg/4.8±0.6 mL RZL-012, Each subject will receive additional study treatments in accordance with the treatment group to which the subject is randomized.

Official Title
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An Open Label Phase 2 Study to Evaluate the Effects of a Local Anesthetic, Anti-inflammatory Medications and Compression Garments on RZL-012-Induced Adverse Events

Conditions
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Submental Fat

Intervention / Treatment
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* Drug: RZL-012
* Drug: RZL-012+Lidacaine injection prior treatment
* Drug: RZL-012+Medrol
* Drug: RZL-012+Celecoxib+Zyrtec
* Drug: RZL-012+facial and neck wrap


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is a male or female subject between the ages of 18 and 65 years, inclusive. Has body mass index (BMI) between >22 kg/m2 and <40 kg/m2. Has SMF bulge that is contiguous and fits to 32±4 injections sites according to a grid with 1 centimeter (cm) distance between injection points. Has grade 3 to 4 of SMF as rated by both the C-CAT and S-CAT. Has stable weight, with no fluctuation of >5 kg in the past 12 months. If female, is not pregnant or breastfeeding based on the following: agree to the use of highly effective contraceptive methods for at least 2 weeks before baseline until 4 weeks after the last day of study drug and a negative serum pregnancy test (ß-hCG) at screening and negative urine pregnancy test at baseline; or is of nonchildbearing potential defined as clinically infertile as the result of surgical sterilization (hysterectomy, bilateral tubal ligation, and/or bilateral oophorectomy); or is confirmed postmenopausal status (defined as either having amenorrhea for ≥ 12 consecutive months without another cause and documented serum follicle-stimulating hormone (FSH) level > 40 mIU/mL or another documented medical condition (e.g., was born without a uterus)) NOTE: The following are considered highly effective contraceptive methods: hormonal oral contraceptives, injectables, and patches; intrauterine devices; double-barrier methods (synthetic condom, diaphragm, or cervical cap used with spermicidal foam, cream, or gel); and male partner sterilization. If male (with or without vasectomy), agree to the use of highly effective contraceptive methods as listed above in criteria 7 as well as to use a barrier method, e.g. condom , from study check-in until 7 days after drug injection. Is willing to avoid strenuous exercise for seven (7) days post treatment. Is able to adhere to the visit schedule and protocol requirements and be available to complete the study. Is willing and able to sign an Institutional Review Board (IRB) approved informed consent form (ICF) indicating that they are aware of the investigational nature of the study. Exclusion Criteria: Is unable to tolerate subcutaneous injections. Has dysfunctional gallbladder activity (e.g., underwent cholecystectomy or cholecystitis). Has any systemic disease including but not limited to gastritis or ulcers, renal dysfunction, hypertension, liver disease, glaucoma, diabetes and/or cardiovascular disease. Has any contraindications to oral corticosteroids (prednisone), NSAIDs (e.g., Celecoxib) or non-sedative antihistamines (e.g. Zyrtec) Has skin laxity (i.e., elastosis, skin crepiness, skin redundancy, skin draping, vertical and/or horizontal skin bands and folds, blunting of cervical mental angle, loss of opposition of skin to underlying neck structures due to skin laxity) that could obscure the evaluation and treatment of SMF. Has any scars, unshaven hair, tattoos, facial hair or jewelry on or near the proposed treatment area. Has presence of structures or confounding factors that may interfere with assessing SMF such as but not limited to enlarged submandibular salivary and/or parotid glands, micrognanthia, chin implant, soft tissue volume augmentation of chin and/or jawline, pronounced platysmal bands and deep necklace lines or presence of facial jowls that could obscure the evaluation of SMF. Has a fat bulge under the chin that is too large to be adequately treated by 32±4 contiguous injections on a 1cm grid . Has a fat bulge under the chin that is of an insufficient volume to allow 32±4 injections within a contiguous 1 cm grid. Has significant history or current evidence of a medical, psychological or other disorder that, in the Investigator's opinion, would preclude enrollment in the study. Has an active bacterial, fungal, or viral infection in the proposed treatment area. Has a pre-existing skin condition in the submental region that, at the Investigator's discretion, may confound evaluation or analysis. Has previously had treatments or surgery in the submentum, such as but not limited to, focused ultrasound, radiofrequency, cryolipolysis, liposuction, sodium deoxycholate, or neck lift. Has pre-existing neurological or gastrointestinal condition leading to dysphagia, dysphonia, or facial nerve palsy. Has Dercum's Disease. Has allergic reactions to injectables Has allergic reactions to Zyrtec or Celecoxib. Has any pre-existing medical condition other than increased SMF that, at the Investigator's discretion, may result in increased submental fullness, such as but not limited to, thyroid enlargement, goiter, cervical lymphadenopathy, etc. Has a planned fat reduction procedure of any variety to the submental region for the duration of the study. Has medication or a history of coagulopathy. Has a history or family history of venous thrombotic disease. Has been treated chronically at least three (3) months prior to study entry with systemic steroids or immunosuppressive drugs. Has been treated chronically at least one (1) week prior to study entry with non-steroidal anti-inflammatory drugs (NSAIDs) Has used anticoagulation therapies that may increase bleeding or bruising (i.e., aspirin, ibuprofen/Celecoxib, warfarin, vitamins, and herbal preparations) for seven (7) days prior to treatment. .Has had treatment with botulinum toxin injections in the neck or chin area within nine (9) months prior to screening. Current participation or participation within three (3) months prior to the start of this study in a drug or other investigational research study.

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RZL-012 50mg/ml<br> | Drug: RZL-012<br>* 50mg/ml drug formulation<br>Drug: RZL-012+Lidacaine injection prior treatment<br>* 5ml lidocaine will be injected 10 minutes before RZL-012 treatment<br>Drug: RZL-012+Medrol<br>* oral Medrol dose pack (8 mg (2 tablets) on Day 1 before treatment followed by 16 mg after treatment (as per Instructions for Use)). From Day 2, a daily tapering off by 4 mg until Day 6 will be administered per Rx Instructions for use<br>Drug: RZL-012+Celecoxib+Zyrtec<br>* 200 mg Celecoxib BID and 10 mg Zyrtec BID on Days 1, 2, 3, 4, 5 and 6<br>Drug: RZL-012+facial and neck wrap<br>* Universal Facial Band<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety - Adverse events follow up | To compare the benefits of lidocaine, Medrol, Celecoxib +Zyrtec or compression dressings on RZL-012-induced adverse events | 84 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy -Change in score according to Clinician chin assessment tool (C-CAT) | To determine the efficacy of RZL-012 vs. RZL-012 with additional treatments on Day 84 versus baseline using the Clinician Chin Assessment Tool (C-CAT). The CAT is composed of 5 points where 0 represents no fat and 4 represent very noticeable bulge and fat that extends beyond the neck | 84 days | 
| Efficacy - Change in score according to Subject chin assessment tool (S-CAT) | To determine the efficacy of RZL-012 vs. RZL-012 with additional treatments on Day 84 versus baseline using the Subject Chin Assessment Tool (S-CAT). The CAT is composed of 5 points where 0 represents no fat and 4 represent very noticeable bulge and fat that extends beyond the neck | 84 days | 
| Efficacy - Reduction in submental fat volume | Reduction from baseline in submental fat volume (mm^3), as measured with MRI in RZL-012 vs. RZL+other treatments treated subjects vs. placebo treated subjects on Day 84 following injection | 84 days |