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Pain control using the injectable dermal filler calcium hydroxylapatite with integral lidocaine for the correction of nasolabial folds
1810
1949
Pain control using the injectable dermal filler calcium hydroxylapatite with integral lidocaine for the correction of nasolabial folds Daniel Schachter, MD, University of Toronto, Cosmetic Dermatology on Bloor, Toronto, Ontario, Canada; Vince Bertucci, MD, University of Toronto, Toronto, Ontario, Canada; Nowell Solish, MD, University of Toronto, private practice, Toronto, Ontario, Canada
Prospective pilot evaluation of a low frequency ultrasound device for transepidermal delivery of topical actives Hema Sundaram, MD, Dermatology, Cosmetic & Laser Surgery, Rockville, MD, United States
Calcium hydroxylapatite microspheres in a carrier gel (CaHA) is FDA-approved for the correction of moderate to severe facial wrinkles and folds, such as nasolabial folds (NLFs). In July 2009, the FDA approved a method for mixing CaHA with lidocaine, which is associated with significant pain reduction and is preferred by patients. A new formulation of CaHA has been developed with the convenience of integral 0.3% lidocaine hydrochloride (CaHA+lidocaine). In a pivotal study, CaHA+lidocaine demonstrated significantly reduced pain immediately after injection when compared to CaHA alone. Secondary objectives of this study were to further assess pain control and aesthetic outcomes. In this multicenter, randomized, split-face, double-blind study, subjects received treatment with CaHA+Lidocaine in one NFL and CaHA alone in the other NLF. Treatment order and side were randomized. No additional anesthesia or other methods to minimize pain were used in either NLF, preinjection or through to the end of a 60-min pain assessment. Pain level was evaluated for each NLF immediately after the injection needle was removed (time zero) and every 15 mins (6 5 mins) after that for 60 mins, and at weeks 1, 2, and 4. Secondary pain control outcomes assessed during this study were a clinically meaningful difference in pain level at time zero [defined as ¼2.0 cm reduction on the 10 cm visual analog pain scale (VAS)]; pain level using the VAS after time zero; and subject pain preference at time zero. Additional endpoints were aesthetic outcome at 1, 2 and 4 weeks and subject preference with respect to aesthetic outcome. 102 subjects completed the study. The majority of enrolled subjects were female (85.3%) and Caucasian (86.3%) with a mean age of 48.85 years. A clinically meaningful reduction in pain ratings immediately after injection was demonstrated in the CaHA+lidocaine-treated NLF versus the CaHA-treated NLF [90.1%; (0.83, 0.95); P \.0001]. A significant reduction in pain ratings at 15, 30, 45, and 60 minutes after injection was achieved in the CaHA+lidocaine-treated NLF compared to the CaHA-treated NLF [(1.06 vs 3.45), (0.73 vs 2.52), (0.48 vs 1.78), (0.31 vs 1.09), respectively; P \.0001]. This pain differential resulted in a stated preference for calcium hydroxylapatite with integral lidocaine. CaHA with integral lidocaine significantly reduces injection site pain immediately after and throughout the first hour after treatment when compared to CaHA alone.
The stratum corneum is impermeable to most hydrophilic and charged molecules, except via limited intercellular transportation. Passive transcellular diffusion of lipophilic molecules is typically limited to a maximum molecular weight of approximately 500 Da. The purpose of this prospective evaluation was to determine clinical utility of a new, non-invasive ultrasound device for delivery of topical actives across the epidermis, and to derive initial data regarding safety, efficacy and tolerability. The device features a sonatrode to which ultrasound is delivered at approximately 30 kHz. When applied to the skin surface, it emits acoustic and air pressure waves. Resultant shearing and jetting forces on the lipid bilayers of cell membranes that create reversible, randomly distributed 25-125 m microchannels in the stratum corneum for up to 30 minutes. Thermal effects facilitate skin permeability and vasodilation. The microchannels permit passage of hydrophobic and hydrophilic topical agents of varying molecular weights. For this prospective pilot evaluation, 10 healthy patients with facial hyperpigmentation were treated for 3 sessions at 3 to 6 week intervals with the low frequency sonophoresis device, combined with a topical, hydroquinone-free formulation containing lignin peroxidase, a fungal enzyme with direct action on melanin. Physician evaluation was with standardized digital 3-D imaging, the validated Melasma Area Severity Index (MASI), and Global Assessment of Improvement Scale (GAIS). Patient evaluation was via GAIS and a satisfaction questionnaire. Patients were instructed to apply broad spectrum sunscreen at home, and permitted to continue topical lignin peroxidase twice a day. Evaluations of digital images and on physician-scored GAIS and MASI demonstrated improvement in facial hyperpigmentation. Notably, patients with previous minimal or slight response to topical lignin peroxidase and sunscreen obtained significant improvement after addition of in-office low frequency sonophoresis. Patient self-evaluation on the GAIS also demonstrated improvement, with good satisfaction on questionnaires. Low frequency sonophoresis was welltolerated, with no adverse events other than transient mild erythema in some patients. Low frequency sonophoresis was safe, effective and well-tolerated in this evaluation. Evidence level would be increased by controlled studies of larger numbers of patients. The technology may also be of value for other topical actives. Alma Lasers provided the use of this device.
100% is Sponsored by Merz North America, Inc.
1721 Phase 2a, randomized, double-blind, placebo-controlled dose-ranging study of repeat doses of collagenase clostridium histolyticum for the treatment of edematous fibrosclerotic panniculopathy (cellulite) Mitchel P. Goldman, MD, Cosmetic Laser Dermatology, San Diego, CA, United States; Neil S. Sadick, MD, Sadick Aesthetic Surgery and Dermatology, New York, NY, United States; Leroy Young, MD, Mercy Health Research, Washington, MO, United States; Gregory J. Kaufman, MD, Auxilium Pharmaceuticals, Chesterbrook, PA, United States; Ted Smith, PhD, Auxilium Pharmaceuticals, Chesterbrook, PA, United States; James P. Tursi, MD, Auxilium Pharmaceuticals, Chesterbrook, PA, United States Background: Edematous fibrosclerotic panniculopathy (EFP; cellulite) is a local disorder in which shortening and fibrosis of subcutaneous collagen septae result in herniation of fat lobules through the dermohypodermal junction, leading to cosmetic alterations of skin topography and uneven, dimpled skin surfaces. Collagenase clostridium histolyticum (CCH) is a combination of 2 collagenolytic enzymes. A phase 1 study of CCH in women with EFP suggested that CCH may improve EFP appearance; adverse events (AEs) were local and generally mild-tomoderate. The current study used a revised injection technique to assess the safety and effectiveness of repeat doses of CCH in the treatment of EFP. Methods: In this phase 2a, randomized, double-blind, placebo-controlled study, women with EFP were randomized to low (0.06 mg), mid (0.48 mg), or high-dose (0.84 mg) CCH or placebo and received up to 3 subcutaneous treatments, ;21 days apart. The treatment site in the posterior thigh or buttock had to have well-defined, evident cellulite dimples. Local and systemic AEs were monitored. Results: 150 women were enrolled; all groups had improved EFP appearance measured by investigator and subject scores on the Global Aesthetic Improvement Scale (GAIS) (modified to evaluate cellulite). Improvements in mid- and high-dose groups were significant vs placebo (P\.05), with mean GAIS scores by investigators at day 73 of 0.9 and 1.1 (mean response of ‘‘improved’’ or better), respectively, vs 0.5 for placebo. 68% of these subjects reported being ‘‘satisfied’’ or ‘‘very satisfied’’ vs 33% for placebo. A post-hoc responder analysis examined investigator and subject responses within subjects (responder ¼ both investigator and subject report GAIS score of ¼ 1, ‘‘improved’’ or better). Of the mid- and high-dose groups, 56% and 65% respectively were considered responders vs 25% for placebo. Positive results were also demonstrated across other subject/physician assessment endpoints, including the Cellulite Severity Item and components of the Cellulite Severity Scale. AEs in ¼25% of subjects were injection site bruising and injection site pain. No drug-related SAEs occurred. Conclusion: CCH demonstrated statistically significant improvements in EFP appearance as measured by both physicians and subjects. CCH was also welltolerated with mostly local, mild-to-moderate AEs. Additional refinement and validation of the modified assessment scales in larger studies is warranted. This study and preparation of the poster was funded by Auxilium Pharmaceuticals.
MAY 2015
820 Randomized, controlled study to assess the complementary efficacy of cosmeceutical therapy in conjunction with neurotoxin and filler injections Steven Dayan, MD, Water Tower Professional Suites, Chicago, IL, United States; Slika Gutierrez, MS, Water Tower Professional Suites, Chicago, IL, United States; Yevgeniy Krol, Skinceuticals Inc, New York, NY, United States; Christian Oresajo, PhD, L’Oreal Research & Innovation, Clark, NJ, United States Background: Studies have shown that strategically placed moderate amounts of fillers and neurotoxins improve one’s appearance and self-esteem. Also topical cosmeceutical products have been shown to improve visible signs of aging. Thus, combination of skin brightening regimen alone or in conjunction with alphahydroxyl pigment balancing peel could serve to complement afacial injections. Objective: The primary goal of the study was to assess the complementary benefits attained by combination of a cosmeceutical skin brightening regimen with neurotoxin and filler injections, for aesthetic improvement and self-esteem enhancement. Methods: This prospective, 12 week, postmarket study of the addition of skincare regimen to neurotoxin and filler injections was conducted to assess the quality of patients’ skin and overall satisfaction among three treatment groups. A total of 20 subjects were randomized into one of three groups. Group 1 (n ¼ 10) received a skin brightening regimen in conjunction with the injections. Group 2 (n ¼ 5) received the skin brightening regimen and alpha-hydroxyl pigment balancing peel every 2 weeks for a total of five peels throughout the study in conjunction with the injections. Group 3 (n ¼ 5), serving as the control group, received a basic skincare regime consisting of a cleanser, moisturizer, and SPF 50 in conjunction with the injections. All subjects were assessed at baseline, week 4, week 8 and week 12 using the Fitzpatrick Wrinkle Assessment Scale (FWAS), Global Aesthetic Improvement Scale (GAIS), and Heatherton & Polivy State Self-Esteem Scale (HPSS). Results: The three groups showed improvement from baseline to week 12 in each assessment. Subjects in groups 1 and 2, who received the skin brightening system consistently showed a greater improvement in assessment scores than subjects in group 3. Subjects in groups 1 and 2 showed 73% more improvement in FWAS and 77% more improvement in GAIS compared to subjects in group 3. HPSS data indicated great improvements in self-esteem of all three groups at week 8 compared to baseline. Conclusion: Findings suggest that the application of the cosmeceutical brightening system with or without the alpha-hydroxyl chemical peel regimen in conjunction with neurotoxin and filler injections offers complementary improvement in the appearance of fine lines, pigmentation, skin tone as well as global aesthetic improvement and self-esteem with a satisfaction that peaks around 8 weeks post injection. 100% is Sponsored by L’Oreal.
J AM ACAD DERMATOL
AB19
1949
Pain control using the injectable dermal filler calcium hydroxylapatite with integral lidocaine for the correction of nasolabial folds Daniel Schachter, MD, University of Toronto, Cosmetic Dermatology on Bloor, Toronto, Ontario, Canada; Vince Bertucci, MD, University of Toronto, Toronto, Ontario, Canada; Nowell Solish, MD, University of Toronto, private practice, Toronto, Ontario, Canada
Prospective pilot evaluation of a low frequency ultrasound device for transepidermal delivery of topical actives Hema Sundaram, MD, Dermatology, Cosmetic & Laser Surgery, Rockville, MD, United States
Calcium hydroxylapatite microspheres in a carrier gel (CaHA) is FDA-approved for the correction of moderate to severe facial wrinkles and folds, such as nasolabial folds (NLFs). In July 2009, the FDA approved a method for mixing CaHA with lidocaine, which is associated with significant pain reduction and is preferred by patients. A new formulation of CaHA has been developed with the convenience of integral 0.3% lidocaine hydrochloride (CaHA+lidocaine). In a pivotal study, CaHA+lidocaine demonstrated significantly reduced pain immediately after injection when compared to CaHA alone. Secondary objectives of this study were to further assess pain control and aesthetic outcomes. In this multicenter, randomized, split-face, double-blind study, subjects received treatment with CaHA+Lidocaine in one NFL and CaHA alone in the other NLF. Treatment order and side were randomized. No additional anesthesia or other methods to minimize pain were used in either NLF, preinjection or through to the end of a 60-min pain assessment. Pain level was evaluated for each NLF immediately after the injection needle was removed (time zero) and every 15 mins (6 5 mins) after that for 60 mins, and at weeks 1, 2, and 4. Secondary pain control outcomes assessed during this study were a clinically meaningful difference in pain level at time zero [defined as ¼2.0 cm reduction on the 10 cm visual analog pain scale (VAS)]; pain level using the VAS after time zero; and subject pain preference at time zero. Additional endpoints were aesthetic outcome at 1, 2 and 4 weeks and subject preference with respect to aesthetic outcome. 102 subjects completed the study. The majority of enrolled subjects were female (85.3%) and Caucasian (86.3%) with a mean age of 48.85 years. A clinically meaningful reduction in pain ratings immediately after injection was demonstrated in the CaHA+lidocaine-treated NLF versus the CaHA-treated NLF [90.1%; (0.83, 0.95); P \.0001]. A significant reduction in pain ratings at 15, 30, 45, and 60 minutes after injection was achieved in the CaHA+lidocaine-treated NLF compared to the CaHA-treated NLF [(1.06 vs 3.45), (0.73 vs 2.52), (0.48 vs 1.78), (0.31 vs 1.09), respectively; P \.0001]. This pain differential resulted in a stated preference for calcium hydroxylapatite with integral lidocaine. CaHA with integral lidocaine significantly reduces injection site pain immediately after and throughout the first hour after treatment when compared to CaHA alone.
The stratum corneum is impermeable to most hydrophilic and charged molecules, except via limited intercellular transportation. Passive transcellular diffusion of lipophilic molecules is typically limited to a maximum molecular weight of approximately 500 Da. The purpose of this prospective evaluation was to determine clinical utility of a new, non-invasive ultrasound device for delivery of topical actives across the epidermis, and to derive initial data regarding safety, efficacy and tolerability. The device features a sonatrode to which ultrasound is delivered at approximately 30 kHz. When applied to the skin surface, it emits acoustic and air pressure waves. Resultant shearing and jetting forces on the lipid bilayers of cell membranes that create reversible, randomly distributed 25-125 m microchannels in the stratum corneum for up to 30 minutes. Thermal effects facilitate skin permeability and vasodilation. The microchannels permit passage of hydrophobic and hydrophilic topical agents of varying molecular weights. For this prospective pilot evaluation, 10 healthy patients with facial hyperpigmentation were treated for 3 sessions at 3 to 6 week intervals with the low frequency sonophoresis device, combined with a topical, hydroquinone-free formulation containing lignin peroxidase, a fungal enzyme with direct action on melanin. Physician evaluation was with standardized digital 3-D imaging, the validated Melasma Area Severity Index (MASI), and Global Assessment of Improvement Scale (GAIS). Patient evaluation was via GAIS and a satisfaction questionnaire. Patients were instructed to apply broad spectrum sunscreen at home, and permitted to continue topical lignin peroxidase twice a day. Evaluations of digital images and on physician-scored GAIS and MASI demonstrated improvement in facial hyperpigmentation. Notably, patients with previous minimal or slight response to topical lignin peroxidase and sunscreen obtained significant improvement after addition of in-office low frequency sonophoresis. Patient self-evaluation on the GAIS also demonstrated improvement, with good satisfaction on questionnaires. Low frequency sonophoresis was welltolerated, with no adverse events other than transient mild erythema in some patients. Low frequency sonophoresis was safe, effective and well-tolerated in this evaluation. Evidence level would be increased by controlled studies of larger numbers of patients. The technology may also be of value for other topical actives. Alma Lasers provided the use of this device.
100% is Sponsored by Merz North America, Inc.
1721 Phase 2a, randomized, double-blind, placebo-controlled dose-ranging study of repeat doses of collagenase clostridium histolyticum for the treatment of edematous fibrosclerotic panniculopathy (cellulite) Mitchel P. Goldman, MD, Cosmetic Laser Dermatology, San Diego, CA, United States; Neil S. Sadick, MD, Sadick Aesthetic Surgery and Dermatology, New York, NY, United States; Leroy Young, MD, Mercy Health Research, Washington, MO, United States; Gregory J. Kaufman, MD, Auxilium Pharmaceuticals, Chesterbrook, PA, United States; Ted Smith, PhD, Auxilium Pharmaceuticals, Chesterbrook, PA, United States; James P. Tursi, MD, Auxilium Pharmaceuticals, Chesterbrook, PA, United States Background: Edematous fibrosclerotic panniculopathy (EFP; cellulite) is a local disorder in which shortening and fibrosis of subcutaneous collagen septae result in herniation of fat lobules through the dermohypodermal junction, leading to cosmetic alterations of skin topography and uneven, dimpled skin surfaces. Collagenase clostridium histolyticum (CCH) is a combination of 2 collagenolytic enzymes. A phase 1 study of CCH in women with EFP suggested that CCH may improve EFP appearance; adverse events (AEs) were local and generally mild-tomoderate. The current study used a revised injection technique to assess the safety and effectiveness of repeat doses of CCH in the treatment of EFP. Methods: In this phase 2a, randomized, double-blind, placebo-controlled study, women with EFP were randomized to low (0.06 mg), mid (0.48 mg), or high-dose (0.84 mg) CCH or placebo and received up to 3 subcutaneous treatments, ;21 days apart. The treatment site in the posterior thigh or buttock had to have well-defined, evident cellulite dimples. Local and systemic AEs were monitored. Results: 150 women were enrolled; all groups had improved EFP appearance measured by investigator and subject scores on the Global Aesthetic Improvement Scale (GAIS) (modified to evaluate cellulite). Improvements in mid- and high-dose groups were significant vs placebo (P\.05), with mean GAIS scores by investigators at day 73 of 0.9 and 1.1 (mean response of ‘‘improved’’ or better), respectively, vs 0.5 for placebo. 68% of these subjects reported being ‘‘satisfied’’ or ‘‘very satisfied’’ vs 33% for placebo. A post-hoc responder analysis examined investigator and subject responses within subjects (responder ¼ both investigator and subject report GAIS score of ¼ 1, ‘‘improved’’ or better). Of the mid- and high-dose groups, 56% and 65% respectively were considered responders vs 25% for placebo. Positive results were also demonstrated across other subject/physician assessment endpoints, including the Cellulite Severity Item and components of the Cellulite Severity Scale. AEs in ¼25% of subjects were injection site bruising and injection site pain. No drug-related SAEs occurred. Conclusion: CCH demonstrated statistically significant improvements in EFP appearance as measured by both physicians and subjects. CCH was also welltolerated with mostly local, mild-to-moderate AEs. Additional refinement and validation of the modified assessment scales in larger studies is warranted. This study and preparation of the poster was funded by Auxilium Pharmaceuticals.
MAY 2015
820 Randomized, controlled study to assess the complementary efficacy of cosmeceutical therapy in conjunction with neurotoxin and filler injections Steven Dayan, MD, Water Tower Professional Suites, Chicago, IL, United States; Slika Gutierrez, MS, Water Tower Professional Suites, Chicago, IL, United States; Yevgeniy Krol, Skinceuticals Inc, New York, NY, United States; Christian Oresajo, PhD, L’Oreal Research & Innovation, Clark, NJ, United States Background: Studies have shown that strategically placed moderate amounts of fillers and neurotoxins improve one’s appearance and self-esteem. Also topical cosmeceutical products have been shown to improve visible signs of aging. Thus, combination of skin brightening regimen alone or in conjunction with alphahydroxyl pigment balancing peel could serve to complement afacial injections. Objective: The primary goal of the study was to assess the complementary benefits attained by combination of a cosmeceutical skin brightening regimen with neurotoxin and filler injections, for aesthetic improvement and self-esteem enhancement. Methods: This prospective, 12 week, postmarket study of the addition of skincare regimen to neurotoxin and filler injections was conducted to assess the quality of patients’ skin and overall satisfaction among three treatment groups. A total of 20 subjects were randomized into one of three groups. Group 1 (n ¼ 10) received a skin brightening regimen in conjunction with the injections. Group 2 (n ¼ 5) received the skin brightening regimen and alpha-hydroxyl pigment balancing peel every 2 weeks for a total of five peels throughout the study in conjunction with the injections. Group 3 (n ¼ 5), serving as the control group, received a basic skincare regime consisting of a cleanser, moisturizer, and SPF 50 in conjunction with the injections. All subjects were assessed at baseline, week 4, week 8 and week 12 using the Fitzpatrick Wrinkle Assessment Scale (FWAS), Global Aesthetic Improvement Scale (GAIS), and Heatherton & Polivy State Self-Esteem Scale (HPSS). Results: The three groups showed improvement from baseline to week 12 in each assessment. Subjects in groups 1 and 2, who received the skin brightening system consistently showed a greater improvement in assessment scores than subjects in group 3. Subjects in groups 1 and 2 showed 73% more improvement in FWAS and 77% more improvement in GAIS compared to subjects in group 3. HPSS data indicated great improvements in self-esteem of all three groups at week 8 compared to baseline. Conclusion: Findings suggest that the application of the cosmeceutical brightening system with or without the alpha-hydroxyl chemical peel regimen in conjunction with neurotoxin and filler injections offers complementary improvement in the appearance of fine lines, pigmentation, skin tone as well as global aesthetic improvement and self-esteem with a satisfaction that peaks around 8 weeks post injection. 100% is Sponsored by L’Oreal.
J AM ACAD DERMATOL
AB19