Comparison of Two Commercial Preparations of Botulinum Toxin Type A

Study Overview
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Brief Summary
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The objective of this study is to compare the action halos of the botulinum toxins (Dysport® and Botox®) using two equivalence-ratios and to gather supportive information, such as more detailed data on the effectiveness in reduction of wrinkles and duration of action on the upper part of the face of both products, trough scales and photographs evaluations.

Detailed Description
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This was a monocentric, prospective, randomized and double-blind study. Fifty nine female patients, presenting with moderate to severe forehead wrinkles, with sweating ability who had never undergone previous BoNT-A injections were enrolled. There were two randomizations, one related to the dose-equivalence (2:1U and 2.5:1U), both reconstituted in the same volume of 0.02 mL per point and another related to the forehead side (left or right) for application of the tested drugs. Baseline, twenty-eight and 112 days later, clinical and photographic assessments, Minor´s test, and electromyographic (EMG) evaluations were performed.

Official Title
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A Phase iv Controlled Randomized Blinded Study on the Anhydrotic Action Halos and Muscle Activity of Two Commercial Preparations Type a Botulinum Toxin (Dysport® and Botox® ) Administered to the Upper Third of the Face

Conditions
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Wrinkles in Frontal Area

Intervention / Treatment
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* Drug: BOTULINUM TOXIN TYPE-A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written Informed Consent (Annex 1) Female Subjects agreeing to take part in all procedures of the study, including botulinum toxin applications, Minor's test, measurement of Evoked Potentials, photographs, etc.), after being fully informed on the objectives and nature of the investigations Subjects aged between 18 and 60 years Subjects presenting with moderate to severe wrinkles on the forehead under maximum voluntary contraction of the m. frontalis Subjects with positive Minor's test showing sweating on the forehead in standardized conditions described in Annex 2 *The Minor's Test will be the last inclusion criterion to be evaluated. Only these patients eligible according to the other inclusion criteria will undergo the Minor's Test to evaluate their sweating on the forehead. The cut off point is a positive Minor's Test (Level +1) - only subjects with Minor's Test (Level +1) will be recruited in the study (Annex 2). Medical history and physical examination which, based on the investigator's opinion, do not prevent the patient from taking part in the study and use the products under investigation Subjects of childbearing age should present a negative urine pregnancy test at baseline and should be using an effective contraceptive method; Availability of the patient throughout the duration of the study (112 days) Subject agrees not to undergo other cosmetic or dermatological procedures during the study Subjects with sufficient schooling and awareness to enable them to cooperate to the degree required by this protocol Exclusion Criteria: Pregnant women or women intending to become pregnant in the next 4 months after screening for eligibility Subjects who are lactating Subjects having undergone botulinum toxin treatment within the last 6 months Subjects participating in other clinical trials Any prior surgery affecting the frontalis and/or orbicularis muscles, prior blepharoplasty or brow lift Any prior cosmetic procedures, including fillers, or scars that may interfere with the study results Subjects presenting fronto-parietal alopecia according to the Norwood-Hamilton classification Subjects with neoplastic, muscular or neurological diseases Subjects using aminoglycoside and penicillamine antibiotics, quinine and Ca2+ channel blockers Subjects with inflammation or active infection in the area to be injected Subjects presenting evident facial asymmetry Subjects with a history of adverse effects, such as sensitivity to the components of the formula, ptosis or any other adverse effect, which in the investigator's opinion should prevent the patient from participating in the study Subjects presenting myasthenia gravis, Eaton-Lambert Syndrome and motor neuron diseases Subjects with coagulation disorders or using anticoagulants Subjects with known systemic autoimmune diseases Subjects with a history of medical treatment non-adherence or showing unwillingness to adhere to the study protocol Any condition that, in the opinion of the investigator, can compromise the evaluation of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BoNT A1 (4U)<br>BoNT A1 (4U): Botulinum toxin A (Dysport®)4 units | Drug: BOTULINUM TOXIN TYPE-A<br>* On Visit 1 (Day 0): Botulinum toxin A (Dysport® and Botox®) will be administered according to an equivalence ratio of 2:1. Both reconstituted in the same volume per point, injected in the forehead determined site. Dysport®: 4 units will be injected in the left or right forehead side. Botox® : 2 units will be injected in the left or right forehead side.(opposite side of dysport injection)<br>* Other names: BoNT A2 = Botox;|
| Active Comparator: BoNT-A2 (2U)<br>BoNT-A2(2U): Botulinum toxin A (Botox®) 2 units | Drug: BOTULINUM TOXIN TYPE-A<br>* On Visit 1 (Day 0): Botulinum toxin A (Dysport® and Botox®) will be administered according to an equivalence ratio of 2:1. Both reconstituted in the same volume per point, injected in the forehead determined site. Dysport®: 4 units will be injected in the left or right forehead side. Botox® : 2 units will be injected in the left or right forehead side.(opposite side of dysport injection)<br>* Other names: BoNT A2 = Botox;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Horizontal Action Halo Diameter at 28 Days | Minor's test permits the visualization of the effect of botulinum toxin in the injected area,also called action halos. Mirror is a computer program that allows, through photogrpahs, measuring the horizontal diameter and the area of action halos. | 28 days | 
| ECMAP in m. Frontialis BoNT A1(4U) X BoNT A2 (2U) | ECMAP(Evoked Compound Muscle Action Potentials) was accessed by an electromyography (EMG) device (TECA Sapphire - TECA Corp., Pleasantville, NY). | 28 days | 
| Horizontal Action Halo Diameter at 112 Days | Minor's test permits the visualization of the effect of botulinum toxin in the injected area,also called action halos. Mirror is a computer program that allows, through photogrpahs, measuring the horizontal diameter and the area of action halos. | 112 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Muscular activity, wrinkles in frontal area, action halos