Journal of Dermatology and Clinical Research

Cite this article: Krochmal LM, Young VL, Locke KW, Gold MH, Cohen SR, et al. (2015) Aesthetic Treatment of Central Abdominal Bulging (CAB) with LIPO-202 (Salmeterol Xinafoate for Injection). J Dermatolog Clin Res 3(3): 1050.

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*Corresponding authorLincoln M Krochmal, Neothetics, Inc. 9191 Towne Centre Drive, Suite 400, San Diego, CA 92122, USA, Tel: 858 750-1008; Email:

Submitted: 22 October 2014

Accepted: 12 March 2015

Published: 20 March 2015

Copyright© 2015 Krochmal et al.

OPEN ACCESS

Keywords•Central Abdominal Bulging (CAB)•Subcutaneous fat•LIPO-202•Salmeterol Xinafoate•Tape measure

Research Article

Aesthetic Treatment of Central Abdominal Bulging (CAB) with LIPO-202 (Salmeterol Xinafoate for Injection)Lincoln M. Krochmal1*, V. Leroy Young2, Kenneth W. Locke1, Michael H. Gold3, Steven R. Cohen4, Scott D. Glazer5, Marina I. Peredo6 and John H. Joseph7

1Department of Dermatology, Neothetics, USA2Department of Plastic Surgery, Mercy Health Research, USA3Department of Dermatology, Tennessee Clinical Research Center and Gold Skin Care Center, USA 4Department of Plastic Surgery, University of California at San Diego School of Medicine, USA 5Department of Dermatology, Glazer Dermatology, USA6Department of Dermatology, Mount Sinai Hospital, USA7Department of Plastic Surgery, UCLA David Geffen School of Medicine, USA

Abstract

Background: Bulging in the periumbilical region of the abdomen due to excess subcutaneous fat is common among non-obese men and women, however, specific clinically-relevant diagnostic criteria have not been established for this condition (referred to as Central Abdominal Bulging (CAB)).

Objective: The objectives of this study were to establish diagnostic criteria for CAB and to evaluate LIPO-202 (Salmeterol Xinafoate for Injection) as a potential treatment for this condition.

Methods: This randomized, placebo-controlled, double-blind clinical study enrolled 513 male and female subjects with a BMI<30 kg/m2 and CAB. Twenty 1.0 mL SC injections of LIPO-202 (0.4, 1.0 or 4.0 µg total weekly dose) or placebo were administered weekly for 8 weeks to the anterior abdomen between axial planes at +35 mm and -70 mm, relative to the umbilicus. Treatment outcomes included patient and clinician ratings of CAB, as well as the measurement of abdominal circumference by a standardized laser-guided tape measure procedure.

Results: LIPO-202 was well-tolerated at all doses; adverse effects were primarily mild and transient injection site events reported at a similar frequency (≤10%) to placebo. Significant reductions in mean abdominal circumference and volume were observed with LIPO-202 (0.4 µg total weekly dose) compared to placebo (-1.6 cm/-192 cc vs. -0.7 cm/-90 cc, respectively, p<0.05). Treatment effects were enhanced in patients that remained weight neutral or lost weight.

Conclusions: Central Abdominal Bulging is a common condition in non-obese subjects that can be defined through specific diagnostic criteria. LIPO-202 produced clinically meaningful reductions in CAB and may offer a novel approach to localized fat reduction.

INTRODUCTIONIn our society, a heightened focus on body aesthetics and

general appearance continues to influence the treatment-seeking behavior of a clinically-distinct group of patients with excessive subcutaneous fat deposits localized to the periumbilical region of the abdomen. Patients refer to this area with terms such as “bulging,” “rolls,” “pooch,” “spare tire,” “bloated,” “paunch,” and “potbelly.” In addition to its visual appearance, patients

express concern about how the area feels to the touch, calling it “flabby” or “jiggly” and refer to the appearance of the area as “unattractive” or “ugly.” In some individuals, concerns over physical appearance or body image regarding the abdominal bulging leads to impairment in self-image, confidence and overall daily functioning due to social inhibition and anxiety [1]. Consequently, many individuals seek treatment for this condition in their desire to achieve a flatter abdomen.

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Although common among men and women across all demographic groups and easily recognized as an undesired aspect of body appearance, this condition presently lacks a clearly defined clinical diagnosis. We believe it is possible to define anatomical parameters which can be used to establish a diagnosis referred to as Central Abdominal Bulging (CAB). CAB presents in non-obese individuals as periumbilical bulging due to an accumulation of excessive subcutaneous fat.

DIAGNOSIS OF CABDiagnostic criteria have been developed for CAB that clearly

differentiates it from obesity. The hallmarks of CAB are:

• BMI (Body Mass Index) < 30 kg/m2 – BMI is calculated from a determination of weight (in kg) and height (in m). Patients with CAB are non-obese; the World Health Organization defines obesity as a condition where a person’s BMI is greater than or equal to 30 kg/m2.

• Focal periumbilical bulging – Localized adiposity of the central abdomen in non-obese subjects that is clinically apparent as a distinctly visible and palpable area of periumbilical soft tissue bulging, often flanked by flat or concave lateral areas.

• Palpable periumbilical subcutaneous fat of up to ~8 cm – Using a pinch test to estimate the skin-fold thickness between the thumb and forefinger (s), the presence of up to ~8 cm of subcutaneous fat retractable from the abdominal musculature(not the result of visceral adiposity) confirms the diagnosis of CAB.

• Absence of rectus diastasis, hernias or any musculoskeletal abnormalities that could account for the periumbilical bulging.

In making the diagnosis of CAB, care should be taken to assure that patients assume proper posture, do not contract their abdomen and that assessment is made on full, natural exhalation. After both visual and palpation assessments have been completed and the diagnosis of CAB is confirmed, the physician can then perform a standard history and physical exam before proceeding to a consideration of treatment options.

TREATMENT OPTIONS FOR CABTreatment of central abdominal bulging in non-obese subjects

is localized to the periumbilical region. Fat in this area is often resistant to diet and exercise; it is a myth that spot reduction of fat is possible through diet and/or exercise [2]. Until recently, the options for treatment of CAB in non-obese patients have been limited to invasive surgical procedures. Lipoplasty (liposuction), one of the top five most popular procedures performed by American Society for Aesthetic Plastic Surgery (ASAPS) members in 2013, was specifically related to abdominal flattening in non-obese subjects with over 350,000 procedures performed annually [3]. The ASAPS defines the ideal candidate for liposuction to be “normal weight with isolated fatty areas [3].”Unfortunately, surgical liposuction (under general anesthesia) carries significant potential risk to a person seeking an aesthetic improvement; two independent surveys of board- certified aesthetic plastic surgeons in the U.S. determined the mortality rate to be

approximately 20 deaths per 100,000 procedures [4]. However, recent improvements in technology and techniques have been reported to reduce the incidence of adverse effects associated with liposuction [5,6]. Liposuction around the umbilicus is also somewhat problematic; small cannulae are required to navigate its contours in order to get uniform fat reduction without creating irregularities (e.g., lumps, dents). In addition, this anatomical location also contains significant amounts of fibrous tissue which makes uniform removal of fat more difficult. Although liposuction remains appropriate as a treatment for diffuse adiposity that extends more broadly beyond the periumbilical region, these difficulties have led clinicians and patients to seek less invasive, less expensive and safer methods of removing unwanted fat from this area without the long associated recovery times.

Beyond liposuction, there are now a number of non-surgical options for non-obese patients seeking aesthetic improvement of their abdomen. At one end of the spectrum are medical devices that deliver some form of energy through the skin to ablate subcutaneous fat cells in the anterior abdomen such as radiofrequency, high intensity focused ultrasound (HIFU), cold (cryolipolysis) or low level laser therapy [7]. These devices all deliver the specified energy, but proof of efficacy and safety in improving abdominal contour has generally been limited to small clinical trials. In many cases (e.g., cryolipolysis, HIFU), use of these devices to ablate fat cells also results in the inflammatory process needed to remove the ablated fat cells from the treated area [8]. This inflammatory process may result in pain, swelling and redness along with the recovery time for the process to complete and time to view aesthetic benefit. In addition, the cost of these devices as well as the disposables required by many must be taken into consideration for each treatment.

At the other end of the spectrum from FDA-cleared devices are injectable drug cocktails known as mesotherapy or lipodissolve. Mesotherapy involves a series of injections of medications that are purported to melt away localized fat deposits. Combinations of drugs such as phosphatidylcholine and deoxycholate (commonly called PC and DC, respectively), DC alone or combinations including other drugs or products such as vitamins, minerals, and herbal extracts may be used [9,10]. Warning letters were issued by FDA to medical spas offering mesotherapy for unfounded claims of efficacy [10,11]. There have also been numerous reports of significant adverse events (e.g., skin necrosis, infections, etc.) due to unregulated mesotherapy [10,11]. Thus, a non-surgical alternative that has an acceptable safety profile and that involves no post- procedure morbidity or recovery period would be an important therapeutic alternative to offer those non-obese patients seeking abdominal flattening. LIPO-202 (Salmeterol Xinafoate for Injection), as described herein, may represent such a novel, non-surgical alternative.

LIPO-202: A New Treatment for CAB

LIPO-202 is a novel injectable form of salmeterol xinafoate designed to produce local, selective fat tissue reduction (pharmaceutical lipoplasty). LIPO-202 is under development for the reduction of CAB in non-obese patients (BMI < 30 kg/m2). LIPO-202 is administered by a physician in less than 5 minutes through a specified number and defined placement of subcutaneous (SC) injections via a fine 30 gauges, ½ inch needle

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across the abdominal treatment area with no anesthetic required and no patient recovery or “down time.”

Salmeterol xinafoate is a highly selective, long-acting β2-adrenergic receptor agonist. Adrenergic receptors play a major role in the regulation of several processes in the body, including fat cell metabolism. Activation of β2-adrenergic receptors located on human fat cells by salmeterol triggers the breakdown of triglycerides in these cells to free fatty acids and glycerol by means of lipolysis (an enzymatic process). Thus, by stimulating lipolysis, the injection of LIPO-202 evenly across the abdomen reduces fat cell volume (shrinks fat cells) and ultimately reduces abdominal bulging without the risk of producing contour irregularities (Figure 1). In this way, LIPO-202 mimics the body’s natural process for reducing local fat stores (and the bulges they create), and unlike many other treatments that ablate fat cells, no painful inflammatory reaction is produced.

METHODSA randomized, double-blind, placebo-controlled study was

conducted to evaluate the safety and efficacy of LIPO-202. This study was reviewed and approved by a central IRB (Chesapeake IRB, Columbia, MD) and written informed consent was received from all study subjects. The study enrolled 513 adult subjects with CAB at 31 investigative sites across the U.S. Subjects were required to be non-obese (BMI < 30 kg/m2), have a focal area of central abdominal bulging due to excess subcutaneous fat (~400 cm2 area around the umbilicus), have adequate skin elasticity, to have at least a rating of “slight bulge, not flat” on both the5-point Patient- and Clinician-Global Abdominal Perception Scales (P-GAPS and C-GAPS) at Screening and Day 1, and who were at least slightly dissatisfied with their abdominal bulging in the treatment area. Subjects were randomized to receive 1 of 3 doses of LIPO-202 (0.4, 1.0, or 4.0 µg total weekly dose) or placebo (0.9% Sodium Chloride Injection, USP) once a week for 8 weeks on Day 1 after all entry criteria had been satisfied. Randomization was based on a computer- generated, site- based randomization schedule, which was distributed to authorized, unblended

drug preparation personnel at each site. Twenty 1 mL weekly SC injections administered via a ½ inch 30 gauge needle were spaced 4 cm apart on the anterior abdomen between axial planes at +35 mm and -70 mm, relative to the umbilicus. Consistent injection placement was assured by the weekly application of a water-based temporary tattoo defining the location of the 20 injection sites. Efficacy endpoints included a Patient- and Clinician-Global Abdominal Perception Scale, a Patient and Clinician Photo numeric Scale (PPnS and CPnS) and duplicate abdominal circumference measurements (taken at +35 mm, 0 and -70 mm, relative to the umbilicus, using a standardized laser-guided tape measurement procedure). A specific set of standardized instructions (e.g., patient positioning, posture, breathing, etc.) were followed for the collection of all ratings and measurements. Designated clinical site personnel were trained in person to perform each procedure; some procedures also included a training video. Designated clinical site personnel were required to demonstrate that they could perform the procedure prior to study initiation. Specific to the laser-guided tape measure procedure, the reproducibility of the procedure beyond what is obtained with a standard manual tape measure was enhanced with the water-based tattoo on the anterior abdomen, a self-tensioning tape measure, a tripod-mounted laser level (Figure 2) and electronic data capture to ensure the independent recording of circumferential measurements. Both the 5-point patient and clinician verbal rating scales (P-GAPS and C-GAPS) that assigned scores ranging from flat to big (or pronounced) bulge, as well as the 6-point patient and clinician photo numeric scales (PPnS and CPnS) that are a match-to-sample task in which an abdominal profile are selected from a series of 6 identical torsos with a progressively larger anterior abdominal bulge were specifically developed and validated to assess treatment effects in non-obese subjects with CAB. Neither patients nor clinicians had access to the others’ scale ratings and neither had access to previous scale scores. Final assessments on all outcome measures were performed 1 week after the last injections (Day 57 + 2 days).

All efficacy analyses used a repeated measures analysis of

Figure 1 Mechanism of action of LIPO-202.

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covariance (ANCOVA) model to determine differences between each active treatment group and placebo. The repeated measures ANCOVA model was performed on change from baseline (CFB) and percent CFB with fixed effects of treatment group, site, P- GAPS at enrollment (“Slight Bulge, Not Flat” or “Bulge” versus “Big Bulge”), time point (class variable), time point by treatment group interaction and baseline value, and a random effect of subject. The compound symmetry structure for the within-subject covariance matrix was used. Differences in the least squares means for each active treatment and placebo were evaluated using Student’s t-test at each time point. The assumption of normality for analyses was assessed with the Shapiro- Wilk statistic and residuals were visually examined for heterogeneity via scatter plots. If either assumption was violated, overall treatment differences were assessed using the same repeated measures ANCOVA, but with the response being rank-transformed CFB. For all responder endpoints, the number and percentage of subjects at each response level were summarized by treatment group. Differences between each active treatment group and placebo were evaluated using a van Elteren test at each time point. The influence of CFB weight on treatment outcomes was evaluated in post-hoc analyses. Change from baseline weight was added to and additional ANCOVA model and treatment effects were determined in subsets by CFB weight (≤ 0 kg, > 0 kg).

RESULTS

Demographics and Safety

Subjects enrolled in the study were primarily female (81%; 418/513), white (86%; 440/513), with a mean age of 38 (18 – 71) years and a mean BMI of 23.4 (18.2 – 29.9) kg/m2. LIPO-202 (0.4 µg (n=132), 1.0 µg (n=124) and 4.0 µg (n=127) total weekly dose) was well tolerated when administered as divided doses (20 SC injections) into abdominal adipose tissue of healthy subjects once a week for 8 consecutive weeks. Ninety-two percent completed the study per protocol; 6 subjects (1%) were lost to follow-up, 4 subjects (<1%) were terminated for protocol violation, 10 subjects (2%) withdrew consent and 21

subjects (4%) withdrew for miscellaneous causes. There were no significant adverse events during this study and no subject discontinued the study due to an adverse event. The most frequently reported treatment-emergent adverse effects possibly or definitely related to study drug were mild and transient injection site events, including hematoma, erythema, contusion, and pain. The incidence of these administration site adverse effects is reported in Table 1 (the single incidence (< 1%) of other adverse events reported randomly across organ systems and all treatment groups are not shown in the table). These injection site events occurred with a similar frequency in subjects in the placebo group and in the LIPO-202 groups and were considered to be related to the typical mechanical trauma of an injection procedure rather than the study drug itself.

Efficacy

Across most outcome measures, the lowest dose of LIPO-202 (0.02 µg/mL; 0.4 µg total weekly dose) was the most efficacious. These results are consistent with previous preclinical and clinical studies which showed that higher and/or more frequent doses were less effective potentially due to tachyphylaxis (data not shown); tachyphylaxis has been demonstrated with salmeterol in the treatment of asthma and COPD [12]. Significant reductions in mean abdominal circumference assessed by the standardized laser-guided tape measurement procedure were observed with LIPO-202 (0.4 µg) compared to placebo (at the umbilicus, -1.6 cm vs. -0.7 cm, p=0.001; Figure 3, Panel A) when measured 1 week after the last injections (Day 57). Because circumference was measured at 3 levels on the abdomen, changes in abdominal volume could be calculated using a formula for conical cylinders (volume = (height*pi)/12*(dbottom2 + dbottom*dtop +dtop2)). LIPO-202 (0.4 µg) produced a significant reduction in abdominal volume compared to placebo (-192 cc vs. -90 cc, p=0.001; Figure 3, panel B).

Mean weight change (-0.2 kg) over the course of the trial was similar across all treatment groups. However, weight change itself had an effect on treatment outcomes. Subjects who were weight neutral or lost weight (≤ 0 kg) from baseline to End-of-Study had enhanced change from baseline and change from placebo treatment effects. For example, in subjects who were weight neutral or lost weight (≤ 0 kg) in the 0.4 µg total weekly dose group, the mean reduction in umbilical circumference increased from -1.6 cm to -2.7 cm from baseline and from -0.9 cm to -1.6 cm relative to placebo (Figure 4, panel A). Similarly, in subjects who were weight neutral or lost weight (≤ 0 kg) in the 0.4 µg total weekly dose group, the mean reduction in abdominal volume (+35 mm to -70 mm, relative to the umbilicus) increased from -192 cc to -329 cc from baseline and from -102 cc to -175 cc relative to placebo (Figure 4, panel B). No differences in mean weight change (±1.0 kg) were noted between treatment groups when subjects were divided between those who remained weight neutral or lost weight (≤ 0 kg) and those who gained weight (> 0 kg) over the course of the study again showing that this modest weight change cannot account for the treatment effects or differences from placebo. Inclusion or exclusion of weight as a factor within the repeated measures ANCOVA statistical model had no effect on the significance of the treatment effects compared to placebo.

Figure 2 Circumference measurements taken with the aid of an abdominal Treatment Area Grid (temporary tattoo), a tripod-mounted laser level and a self-tensioning tape measure.

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Study Day

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29 57 29 57

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Change in Abdominal Volume(+35 to -70 mm, relative to the umbilicus)

*p=0.001

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Figure 3 Reductions in abdominal circumference at the umbilicus (panel A) and volume in the treatment area (+35 mm to -70 mm, relative to the umbilicus) (panel B) produced by LIPO-202 compared to placebo.

Study Day

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Figure 4 Effects of weight change on reductions in abdominal circumference at the umbilicus (panel A) and volume in the treatment area (+35 mm to -70 mm, relative to the umbilicus) (panel B) produced by LIPO-202 compared to placebo.

Adverse EventtDose LIPO-202

Placebo(n=130)

0.4 µg(n=132)

1.0 µg(n=124)

4.0 µg(n=127)

Any Adverse Event Definitely or Possibly Related to Study Drug 13 (10%) 14 (11%) 15 (12%) 15 (12%)

Administration Site Conditions 7 (5%) 11 (8%) 12 (10%) 11 (9%)

Injection Site Hematoma (bruising) 3 (2%) 7 (5%) 8 (6%) 8 (6%)

Injection Site Erythema 3 (2%) 3 (2%) 2 (2%) 0 (0%)

Injection Site Hemorrhage 2 (2%) 0 (0%) 0 (0%) 0 (0%)

Injection Site Pain 3 (2%) 4 (3%) 3 (2%) 2 (2%)

Injection Site Pruritus 1 (<1%) 0 (0%) 0 (0%) 0 (0%)

Injection Site Discoloration 0 (0%) 1 (< 1%) 0 (0%) 0 (0%)

Injection Site Induration 0 (0%) 0 (0%) 1 (< 1%) 0 (0%)

Localized Edema 0 (0%) 0 (0%) 1 (< 1%) 0 (0%)

Table 1: Treatment-Emergent Adverse Effects Definitely or Possibly Related to Study Drug.

Efficacy was also evaluated using rating scales validated for the purpose of assessing changes in CAB. Subjects in the LIPO-202 0.4 µg total weekly dose treatment group showed consistent mean reductions from baseline across all rating instruments (P-GAPS, C-GAPS, PPnS, CPnS). One way to define treatment benefit is to identify responders on each scale (e.g., a 1- or

2-point (grade) improvement). To further ensure that treatment effects are real, composite analyses are often performed. In the composite, for a subject to be considered a responder, both the patient and the clinician are required to report an improvement. For example, there were significantly more responders on LIPO-202 (0.4 µg) compared to placebo on a composite that requires a

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% R

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10

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% 1-Point P-GAPS/2-Point CPnSComposite Responders at Day 57

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% R

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2

4

6

8

10Placebo0.4 µg LIPO-202

% 2-Point P-GAPS/2-Point CPnSComposite Responders at Day 57

*p<0.05

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Figure 5 Increase in the percentage of composite 1-point P-GAPS and 2-point CPnS responders (panel A) and increase in the percentage of composite 2-point P-GAPS and 2-point CPnS responders with LIPO-202 (0.4 µg total weekly dose) compared to placebo.

Figure 6 Example of responders to LIPO-202 treatment: panel A (37 y.o. F, Baseline BMI=25.8 kg/m2, treated with 0.4 µg LIPO-202 at screening (left) and End-of-Study (Day 57) (right)); panel B (30 y.o. M, Baseline BMI=24.9 kg/m2,treated with 4.0 µg LIPO-202 at screening (left) and End-of-Study (Day 57) (right)).

subject to report a 2-point (grade) improvement on the P-GAPS and a clinician to report a 2-point improvement on the CPnS for that same subject (Figure 5, Panel B).

Although the % responders to LIPO-202 appear relatively low by this very stringent definition of a composite responder, a 1-point (grade) improvement on these rating scales may be clinically meaningful. For example, available data suggest that a 1-point improvement on the P-GAPS is clinically meaningful. With a composite responder defined as a 1-point improvement on the P-GAPS and a 2-point improvement on the CPnS, the % responders to LIPO-202 (0.4 µg) climbs to 16% (Figure 5, Panel A) and to 22% among subjects who were weight neutral or lost weight (≤ 0 kg) over the course of the study. Examples of two LIPO-202 treatment responders are presented in Figure 6 (panel A and B) showing anterior and lateral views at screening and at End-of-Study (Day 57).

DISCUSSIONCentral abdominal bulging (CAB) is common in non-obese

men and women. Although both patients and clinicians use a variety of terms like “pooch” and “rolls” that is “jiggly” and “flabby” to describe the condition, a clinically-relevant diagnosis of CAB can be defined using a specific set of diagnostic criteria. The hallmarks of the CAB diagnosis include a focal bulge centered on the umbilicus, often flanked by flat or concave lateral areas, with up to approximately 8 cm of palpable subcutaneous fat in non-obese subjects. Although this condition is common across all demographic groups, the degree to which it is considered to be problematic is highly dependent on individual perception. As a result of CAB, some individuals concerns over physical appearance or body image regarding the abdominal bulging leads to impairment in self-image, confidence and overall daily functioning due to social inhibition and anxiety [1]. Treatment options have traditionally been limited to surgical liposuction. However, as with any surgical procedure, there is risk of morbidity and mortality. In addition, there is considerable recovery time, as well as time to aesthetic benefit. Many of the newer energy-based medical devices are non-invasive, but due to the inflammatory

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Krochmal LM, Young VL, Locke KW, Gold MH, Cohen SR, et al. (2015) Aesthetic Treatment of Central Abdominal Bulging (CAB) with LIPO-202 (Salmeterol Xin-afoate for Injection). J Dermatolog Clin Res 3(3): 1050.

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process initiated by the damage or ablation of fat cells with some devices, recovery time between treatment sessions is also required. LIPO-202 is a novel, non-ablative alternative to liposuction and energy-based medical devices for the treatment of CAB. Rather than removing or ablating subcutaneous fat cells, LIPO-202 stimulates physiologic lipolysis, thereby shrinking fat cells resulting in abdominal flattening. In clinical testing, LIPO-202 administered as twenty 1 mL SC injections once a week for 8 weeks produced significant reductions in abdominal circumference and volume compared to placebo that was recognized by both subjects and clinicians. Significantly, this was achieved without anesthetics/painkillers, “down time” or risk of contour irregularities. Although very small mean weight changes were observed in the clinical study, treatment effects were enhanced in those subjects who remained weight neutral or who lost weight; it is only logical that little improvement was seen in abdominal profile in subjects who gained weight. Treatment effects were observed with only mild and transient injection site reactions that occurred at the same rate as with placebo injections, suggesting that these adverse events are related to the typical mechanical trauma of an injection procedure rather than to the study drug itself.

CONCLUSIONSCentral Abdominal Bulging (CAB) is a common condition

in non-obese subjects that can be defined through specific diagnostic criteria. LIPO-202 produced clinically meaningful reductions in CAB and may offer a novel, non-invasive and non-ablative approach to localized fat reduction.

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