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This is an open-label and phase IV study of full face injections of variable doses of botulinum toxin type A (BT-A). As it is an open-label and not blind study, both investigator and subjects will know the injection local and doses of the study drug. Patients will be randomized into 3 different groups. Each group will receive a specific dose according with the indication evaluated by the investigator. Six visits will be schedule in this study.
4.2 Methodology
4.2.1 Patient evaluation After providing written informed consent, subject's eligibility will be assessed at a Screening Visit. The subject's general medical history will be recorded. This includes demographic data, history of surgical and cosmetic procedures, dermatological assessment, physical examination, and prior concomitant medications. A pregnancy test will also be performed.
4.2.1.1 Severity of wrinkles
One sub-investigator will rate the wrinkles with the following validated severity scales for the main areas of the face at Baseline, Week 4, Week 8, Week 16 and Week 24:
4.2.1.2 Standard set of photographs will be taken
At Screening , 2, 3, 4 and 5 visits, photographs will be taken:
All the photographs will be taken in a standardized photographic mode with fixed position of the camera. A guideline with examples of standardized photos with delimit standardized positions will be provided to the person responsible to take the photos.
In the photographs, each research subject will be identified by a tag containing a reference to the study, the number of the research subject and the control date. The research subjects should wash their faces before the photographic procedure to remove excess oil and all make up will be removed. All the pictures will be taken at the same room and under same parameters.
The photograph set consist of
At the end of the study, two independent evaluators (dermatologists) will assess before and after pictures in a blinded manner. This evaluation will be done to assess the efficacy of BT-A in the injected areas not assessed by the scales.
4.2.3 Groups of treatment
Subjects will be assigned to one of the three following treatment groups, according with the total dose received in visit 1:
4.2.4 Reconstitution of the study product and Treatment Administration An independent, experienced and registered pharmacist will be the assigned to carry through the reconstitution of the products. She will prepare the dilutions and the syringes of the product (DYSPORT®) immediately prior to the injections.
The dilutions of DYSPORT® 500 units per vial will be made with 2 mL of 0.9% sterile saline, using 3 mL syringes and a 21 gauge needle, giving a concentration of 250 units/mL or 2.5 units/0.01 mL of the reconstituted product.
An experienced dermatologist in the use of botulinum toxins (principal investigator - DH) will perform all the injections according to the indications and total number of units that will be injected according to the treatment plan, which aims to obtain the best results. She will only perform the injections and will not participate in other phases of this study.
The application of the BT-A will be made with Becton, Dickinson and Company (BD) Ultra-fine II 0.3 cc syringes, with a 29 gauge needle, 0.5 cm in length (short needle).
Immediately after the application, the side effects will be verified and if needed, will be registered and managed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 125 to 170 IU of "'Botulinum toxin' " | Active Comparator | group with intervention of 125 to 170 IU of 'Botulinum toxin' |
|
| 171 to 210 IU of 'Botulinum toxin' | Active Comparator | Patients who have received 171 to 210 IU of 'Botulinum toxin' |
|
| 211 to 250 IU of Botulinum toxin | Active Comparator | Patients who have received 211 to 250 U of Botulinum toxi' |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Botulinum toxin | Drug | Drug: Botulinum toxin Indications for eligibility and total doses that will be applied in each part of the face, at visit 1: Upper face:
Mid face:
Lower face:
Patients will be allocated in each group and receive the doses described above at visit 1. At visit 2, all the patients will receive a touch-up of a standard dose of 25 U, distributed on the treated areas according patient's needs. |
| Measure | Description | Time Frame |
|---|---|---|
| Wrinkles' Severity (Forehead) | Facial Wrinkle Scale: 0 - none, 1 - mild; 2 - moderate; 3 - severe | Baseline; Week 4; Week 16; Week 20; Week 24 |
| Wrinkles' Severity (Glabella) | GLADYS study Atlas: 0 - no wrinkles, 1 - mild wrinkles; 2 - moderate wrinkles; 3 - severe wrinkles | Baseline; Week 4; Week 16; Week 20; Week 24 |
| Wrinkles' Severity (Periocular [Crow's Feet]) | Photonumeric Atlas for the Assessment of Crow's Feet Severity: 0 - none, 1 - mild; 2 - moderate; 3 - severe | Baseline; Week 4; Week 16; Week 20; Week 24 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Doris M Hexsel, MD | Brazilian Center for Studies in Dermatology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brazilian Center for Studies in Dermatology | Porto Alegre | Rio Grande do Sul | 90570-040 | Brazil |
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| ID | Title | Description |
|---|---|---|
| FG000 | 125 to 170 Units of Botulinum Toxin Type A | Subjects have received the lower dose of Botulinum Toxin type A |
| FG001 | 171 to 210 Units of Botulinum Toxin Type A | Subjects have received the intermediate dose of Botulinum Toxin type A. |
| FG002 | 211 to 250 Units of Botulinum Toxin Type A | Subjects have received the higher dose of Botulinum Toxin type A. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Group 1 | Subjects have received the lower dose of Botulinum Toxin type A, between 125 to 170 units of Botulinum Toxin type A. |
| BG001 | Group 2 | Subjects have received the intermediate dose of Botulinum Toxin type A, between 171 to 210 units of Botulinum Toxin type A. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Wrinkles' Severity (Forehead) | Facial Wrinkle Scale: 0 - none, 1 - mild; 2 - moderate; 3 - severe | Patients in each visit. | Posted | Mean | Standard Deviation | units on a scale | Baseline; Week 4; Week 16; Week 20; Week 24 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 125 to 170 Units of Botulinum Toxin Type A | Subjects have received the lower dose of Botulinum Toxin type A. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Doris Hexsel | Brazilian Center for Studies in Dermatology | 555130262633 | cientifico@cbed.org.br |
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| ID | Term |
|---|---|
| D001905 | Botulinum Toxins |
| C542869 | abobotulinumtoxinA |
| ID | Term |
|---|---|
| D008666 | Metalloendopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
| D006867 | Hydrolases |
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|
| BG002 | Group 3 | Subjects have received the higher dose of Botulinum Toxin type A, between 211 to 250 units of Botulinum Toxin type A |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | 211 to 250 Units of Botulinum Toxin Type A | Subjects were treated with a total dose of 211 to 250 units of Botulinum Toxin type A on facial indications in upper, middle and lower face. |
|
|
|
| Primary | Wrinkles' Severity (Glabella) | GLADYS study Atlas: 0 - no wrinkles, 1 - mild wrinkles; 2 - moderate wrinkles; 3 - severe wrinkles | Patients in each visit. | Posted | Mean | Standard Deviation | units on a scale | Baseline; Week 4; Week 16; Week 20; Week 24 |
|
|
|
|
| Primary | Wrinkles' Severity (Periocular [Crow's Feet]) | Photonumeric Atlas for the Assessment of Crow's Feet Severity: 0 - none, 1 - mild; 2 - moderate; 3 - severe | Patients in each visit. | Posted | Mean | Standard Deviation | units on a scale | Baseline; Week 4; Week 16; Week 20; Week 24 |
|
|
|
| 0 |
| 26 |
| 0 |
| 26 |
| EG001 | 171 to 210 Units of Botulinum Toxin Type A | Subjects have received the intermediate dose of Botulinum Toxin type A. | 0 | 29 | 0 | 29 |
| EG002 | 211 to 250 Units of Botulinum Toxin Type A | Subjects have received the higher dose of Botulinum Toxin type A. | 0 | 30 | 0 | 30 |
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| D004798 |
| Enzymes |
| D045762 | Enzymes and Coenzymes |
| D045726 | Metalloproteases |
| D001426 | Bacterial Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |
| D001685 | Biological Factors |
|
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| Week 20 |
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| Week 24 |
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| Week 20 |
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| Week 24 |
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