Efficacy and Safety of a New Botulinum Toxin Type A for Treatment of Facial Expression Lines

Wrinkles Clinical Trial

Official title:

Randomized Study of Clinical Non-inferiority of Medicine Botulift (Laboratório Químico Farmacêutico Bergamo Ltd.) Compared to Botox ® (Allergan Inc.) in the Improvement of Wrinkles in the Facial Region.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01180348
• Other study ID #: TOXBER0610
• Status: Completed
• Phase: Phase 3
• First received: August 10, 2010
• Last updated: March 3, 2016
• Start date: August 2011
• Est. completion date: September 2012

Study information

• Verified date: March 2016
• Source: L.A.L Clinica Pesquisa e Desenvolvimento Ltda.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Health Surveillance Agency
• Study type: Interventional

Clinical Trial Summary

The dermatological treatment for reducing facial wrinkles with injectable drug Botulift (botulinum toxin type A - Laboratório Químico Farmacêutico BergamoLtd.) has a not inferior activity when compared with Botox ® (botulinum toxin - Allergan Inc.) in clinical trials.

Description:

The study will evaluate non-inferiority in clinical improvement in the intensity of expression lines over 16 weeks of drug Botulift (Laboratório Químico Farmacêutico Bergamo Ltd.) compared with Botox ® (Allergan Inc.). So that the homogeneity of the group opted to use in female patients with glabellar wrinkles grade 2 (moderate) and 3 (severe) Scale Standard Facial Wrinkles, established by Honecker et al. (2003). The first area of the face perceived in mime is the glabellar complex, located in the space between the eyebrows, wrinkles eventually show (Almeida et al., 2010).

Patients will be evaluated at each visit, the doctor Principal Investigator and digital photos of the glabellar region at maximum contraction and relaxation will be obtained using the apparatus Visia (Canfield Imaging Systems, version 4.0.2) for further analysis by random team dermatologists.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 192
• Est. completion date: September 2012
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Patients who agree with all study procedures and sign for their own free will the TCLE;

• Adult patients were female between 18 and 65 years, regardless of social condition;

• between skin phototype I and IV;

• With good mental and physical health;

• Patients who have not been treated with botulinum toxin type A;

• Patients who agree to abstain from physical activity for a period of 24 hours, previous and subsequent to the initiation of the study;

• Patients presenting at screening visit, wrinkles in the glabellar region between classes 2 and 3 of Table Wrinkles Pattern Classification, which is diagnosed clinically by the dermatologist.

Exclusion Criteria:

• Patients who are in classes 0 and 1 of the Table Pattern Classification Wrinkle;

• Patients who have disorders or diseases that might interfere with neuromuscular function (myasthenia gravis or Lambert-Eaton syndrome);

• Patients being treated with antibiotics (aminoglycosides) and muscle relaxants;

• Patients with pre-existing conditions such as ptosis or scars in the area to be assessed, as they may endanger the health of the patient and the results of the study;

• Patients who have made treatments fill in the glabellar region (retinoic acid, collagen);

• Patients who have been treated in the dermatological peeling úlitmos three months;

• Patients are using treatments dermacosmetics agents anti age (vitamin C pure retinoids flavanoids acid hyaluronic others) or used past 3 months

• Patients with known hypersensitivity to any component of the study drug;

• Pregnant or lactating women;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Wrinkles

Intervention

Drug:
• Botulift
Application of 90 U of Botulift divided in 3 applications on each side of the face in fifteen predetermined sites in three regions of the face (front, glabellar, periocular).
• Botox
Application of 90 U of Botox divided in 3 applications on each side of the face in fifteen predetermined sites in three regions of the face (front, glabellar, periocular).

Locations

Country	Name	City	State
Brazil	LAL Clinica Pesquisa e Desenvolvimento Ltda	Valinhos	Sao Paulo

Sponsors (2)

Lead Sponsor	Collaborator
L.A.L Clinica Pesquisa e Desenvolvimento Ltda.	Laboratório Químico Farmacêutico Bergamo Ltda.

Country where clinical trial is conducted

Brazil, 

References & Publications (26)

Ascher B, Rzany BJ, Grover R. Efficacy and safety of botulinum toxin type A in the treatment of lateral crow's feet: double-blind, placebo-controlled, dose-ranging study. Dermatol Surg. 2009 Oct;35(10):1478-86. doi: 10.1111/j.1524-4725.2009.01261.x. Epub 2009 Jul 20. — View Citation

Beer KR. Comparative evaluation of the safety and efficacy of botulinum toxin type A and topical creams for treating moderate-to-severe glabellar rhytids. Dermatol Surg. 2006 Feb;32(2):184-97. — View Citation

Carruthers A, Carruthers J, Cohen J. A prospective, double-blind, randomized, parallel- group, dose-ranging study of botulinum toxin type a in female subjects with horizontal forehead rhytides. Dermatol Surg. 2003 May;29(5):461-7. — View Citation

Carruthers JA, Lowe NJ, Menter MA, Gibson J, Nordquist M, Mordaunt J, Walker P, Eadie N; BOTOX Glabellar Lines I Study Group. A multicenter, double-blind, randomized, placebo-controlled study of the efficacy and safety of botulinum toxin type A in the treatment of glabellar lines. J Am Acad Dermatol. 2002 Jun;46(6):840-9. — View Citation

Carruthers JD, Lowe NJ, Menter MA, Gibson J, Eadie N; Botox Glabellar Lines II Study Group. Double-blind, placebo-controlled study of the safety and efficacy of botulinum toxin type A for patients with glabellar lines. Plast Reconstr Surg. 2003 Sep 15;112(4):1089-98. — View Citation

De Boulle K, Fagien S, Sommer B, Glogau R. Treating glabellar lines with botulinum toxin type A-hemagglutinin complex: a review of the science, the clinical data, and patient satisfaction. Clin Interv Aging. 2010 Apr 26;5:101-18. Review. — View Citation

Dolly, JO. Therapeutic and Research Exploitation of Botulinum Neurotoxins. Eur J Neurol. 1997;4:S5-10.

Ferreira LM, Filho ST, Costa RO, Godoy A, Steiner D, Fleissig L, et al. Eficácia e tolerabilidade de uma nova toxina botulínica tipo A para tratamento estético de rugas faciais dinâmicas: estudo multicêntrico prospectivo de fase III. Surgical & Cosmetic Dermatology 2009;1(2): 58-63.

Filho ST, Bagatin E, Monteiro EO, Pinheiro MVB, Hassun KM. Eficácia e segurança da neurotoxina botulínica tipo A* no tratamento de linhas de expressão glabelares. RBM rev. bras. med;65(n.esp):28-33, out. 2008.

Gracies JM, Simpson DM. Botulinum toxin therapy. Neurologist 6:98,2000.

Hexsel D, Mazzuco R, Dal'Forno T, Kraemer C, Lima MM, Prado DZ. Botulinum toxin for Facial Wrinkles: History and Future. Expert Rev. Dermatol. 2(4), 417 - 426 (2007).

Honeck P, Weiss C, Sterry W, Rzany B; Gladys study group. Reproducibility of a four-point clinical severity score for glabellar frown lines. Br J Dermatol. 2003 Aug;149(2):306-10. — View Citation

Jankovic J, Brin MF. Botulinum toxin: historical perspective and potential new indications. Muscle Nerve Suppl. 1997;6:S129-45. — View Citation

Jones D, Carruthers J, Narins RS, Coleman WP 3rd, Harrington L, Brandt FS, Cohen JL. Efficacy of incobotulinumtoxinA for treatment of glabellar frown lines: a post hoc pooled analysis of 2 randomized, placebo-controlled, phase 3 trials. Dermatol Surg. 2014 Jul;40(7):776-85. doi: 10.1111/dsu.0000000000000001. — View Citation

Kim K, Shin HI, Kwon BS, Kim SJ, Jung IY, Bang MS. Neuronox versus BOTOX for spastic equinus gait in children with cerebral palsy: a randomized, double-blinded, controlled multicentre clinical trial. Dev Med Child Neurol. 2011 Mar;53(3):239-44. doi: 10.1111/j.1469-8749.2010.03830.x. Epub 2010 Nov 18. — View Citation

Lemperle G, Holmes RE, Cohen SR, Lemperle SM. A classification of facial wrinkles. Plast Reconstr Surg. 2001 Nov;108(6):1735-50; discussion 1751-2. — View Citation

Nigam PK, Nigam A. Botulinum toxin. Indian J Dermatol. 2010;55(1):8-14. doi: 10.4103/0019-5154.60343. — View Citation

Rappl T, Parvizi D, Friedl H, Wiedner M, May S, Kranzelbinder B, Wurzer P, Hellbom B. Onset and duration of effect of incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA in the treatment of glabellar frown lines: a randomized, double-blind study. Clin Cosmet Investig Dermatol. 2013 Sep 24;6:211-9. doi: 10.2147/CCID.S41537. eCollection 2013. — View Citation

RDC 55 - Agência Nacional de Vigilância Sanitária. Registro de Produtos Biológicos | Bases Legais e Guias - Coletânea -459p.: il.; graf.; tab. ISBN.

Small R. Botulinum toxin injection for facial wrinkles. Am Fam Physician. 2014 Aug 1;90(3):168-75. Review. — View Citation

Sposito MMM. Toxina botulínica do tipo A: mecanismo de ação. Acta Fisiatr. 2009;16(1):25-37.

Wollmer MA, de Boer C, Kalak N, Beck J, Götz T, Schmidt T, Hodzic M, Bayer U, Kollmann T, Kollewe K, Sönmez D, Duntsch K, Haug MD, Schedlowski M, Hatzinger M, Dressler D, Brand S, Holsboer-Trachsler E, Kruger TH. Facing depression with botulinum toxin: a randomized controlled trial. J Psychiatr Res. 2012 May;46(5):574-81. doi: 10.1016/j.jpsychires.2012.01.027. Epub 2012 Feb 24. — View Citation

Won CH, Lee HM, Lee WS, Kang H, Kim BJ, Kim WS, Lee JH, Lee DH, Huh CH. Efficacy and safety of a novel botulinum toxin type A product for the treatment of moderate to severe glabellar lines: a randomized, double-blind, active-controlled multicenter study. Dermatol Surg. 2013 Jan;39(1 Pt 2):171-8. doi: 10.1111/dsu.12072. — View Citation

Yang GH, Jung HH. A new botulinum toxin potentially bioequivalent to onabotulinumtoxinA: are there any differences at all? Dermatol Surg. 2013 Jan;39(1 Pt 2):165-70. doi: 10.1111/dsu.12073. Review. Erratum in: Dermatol Surg. 2013 Jun;39(6):965. — View Citation

Yoon JS, Kim JC, Lee SY. Double-blind, randomized, comparative study of Meditoxin versus Botox in the treatment of essential blepharospasm. Korean J Ophthalmol. 2009 Sep;23(3):137-41. doi: 10.3341/kjo.2009.23.3.137. Epub 2009 Sep 8. — View Citation

Zagui RM, Matayoshi S, Moura FC. [Adverse effects associated with facial application of botulinum toxin: a systematic review with meta-analysis]. Arq Bras Oftalmol. 2008 Nov-Dec;71(6):894-901. Review. Portuguese. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall improved assessment of hyperkinetic facial lines in a state of relaxation and maximal contraction through the Honeck's scale and photographic images obtained by equipment Visia Digital Compexton Analysis (Canfield Imaging Systems, version 4.0.2)	The non-inferiority of T group compared to the group Co was demonstrated in evaluations in a state of relaxation and maximal contraction in the PP analysis population, because as defined for the study, the lower limits of 95% of the mean of these assessments (-2 , 7% and -5.4%) are contained within the non-inferiority limit set at -10%.	after 30 days of application	Yes
Secondary	Length of stay of the effect of botulinum toxin A (Test and Comparator)	The action of both treatments decreases over time and there is no significant difference between the two treatments.	during the 24-week period	Yes
Secondary	Safety of both botulinum toxin A	The occurrence of adverse events was similar in both groups.	during the whole period	Yes