Fields Of Effects Of Two Commercial Preparations Of Botulinum Toxin Type A At Equal Labeled Unit Doses

• Sponsor: Brazilan Center for Studies in Dermatology (Other)
• Overall Status: Completed
• CT.gov ID: NCT01732809
• Collaborator: (none)
• Enrollment: 19
• Location: 1
• Arms: 2
• Duration (Months): 10
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the fields of anhydrotic effect (FAE) of abobotulinumtoxinA and onabotulinumtoxinA at the same labeled unit dose (1:1 units), comparing both sweat gland and muscle activity.

Condition or Disease	Intervention/Treatment	Phase
Skin Wrinkling	Drug: AbobotulinumtoxinA (ABO); Drug: OnabotulinumtoxinA (ONA)	Phase 4

Detailed Description

This is a prospective, single-center, randomized, double-blind study. All participants were recruited from a research center in Porto Alegre, Brazil, and provided written informed consent. The purpose of this study is to assess the fields of anhydrotic effect (FAE) of abobotulinumtoxinA and onabotulinumtoxinA at the same labeled unit dose (1:1 units), comparing both sweat gland and muscle activities. Nineteen patients were enrolled and evaluations were performed at baseline and 28 days after treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: Fields of Effects of Two Commercial Preparations of Botulinum Toxin Type A at Equal Labeled Unit Doses
• Study Start Date: Jan 1, 2011
• Actual Primary Completion Date: Nov 1, 2011
• Actual Study Completion Date: Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: abobotulinumtoxin A Patients were randomized to the side of the forehead (left or right) in which the products were administered. All the patients received abobotulinumtoxin A in one of the sides of the forehead.	Drug: AbobotulinumtoxinA (ABO); Isovolumetric (0.02 mL) doses of 2 units of abobotulinumtoxinA injected on one side of the forehead.; Other Names: Dysport®
Active Comparator: onabotulinumtoxin A Patients were randomized to the side of the forehead (left or right) in which the products were administered. All the patients received onabotulinumtoxin A in one of the sides of the forehead.	Drug: OnabotulinumtoxinA (ONA); Isovolumetric (0.02 mL) doses of 2 units of onabotulinumtoxinA injected on the other side of the forehead.; Other Names: Botox®

Outcome Measures

Primary Outcome Measures

1. Horizontal Diameter of the Fields of Anhidrotic Effect [28 days]

   The Horizontal Diameter of the Fields of Anhidrotic Effect were measured with Mirror Medical Imaging Software (Canfield Scientific, Inc., Parsippany, NJ) The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The reaction of iodine and starch with the sweat (Minor's test) allows visualizing the field of anhidrotic effects and measuring them. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FAE are observed at baseline.

2. Vertical Diameter of the Fields of Anhidrotic Effect [28 days]

   The Vertical Diameter of the Fields of Anhidrotic Effect were measured with Mirror Medical Imaging Software (Canfield Scientific, Inc., Parsippany, NJ) The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The reaction of iodine and starch with the sweat (Minor's test) allows visualizing the field of anhidrotic effects and measuring them. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FAE are observed at baseline.

3. Area of the Fields of Anhidrotic Effect [28 days]

   The area of the Fields of Anhidrotic Effect were measured with Mirror Medical Imaging Software (Canfield Scientific, Inc., Parsippany, NJ) The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The reaction of iodine and starch with the sweat (Minor's test) allows visualizing the field of anhidrotic effects and measuring them. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FAE are observed at baseline.

Secondary Outcome Measures

1. Wrinkle Severity Scale (WSS) at Maximum Contraction [Baseline and 28 days]

   It is a 4-point validated scale for forehead lines: 0 - None - Mild - Moderate - Severe The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The muscular effect reduction can be observed by the reduction of facial lines. Wrinkle scales are used to grade the muscular effects of botulinum toxin. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FME are observed at baseline.

2. Wrinkle Severity Scale (WSS) at Rest [Baseline and 28 days]

   It its a 4-point validated scale for forehead lines: 0 - None - Mild - Moderate - Severe The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The muscular effect reduction can be observed by the reduction of facial lines. Wrinkle scales are used to grade the muscular effects of botulinum toxin. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FME are observed at baseline.

3. Evoked Compound Muscle Action Potentials (ECMAP) [Baseline and 28 days]

   Amplitude of the evoked compound muscle action potentials in the frontalis muscle on stimulation of the facial nerve performed at baseline and visit 2 using surface electrodes on the forehead and electrical stimulation of the facial nerve according to standard neurophysiologic procedures. The amplitude of the ECMAP was performed by an experienced neurologist using an electromyography device (Teca Sapphire; Teca Corp).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Signed consent

2. Female subjects aged between 18 to 60 years

3. Phototype I to IV

4. Moderate to severe wrinkles in the forehead region on maximal contracture of the frontalis muscle according to the Wrinkle Severity Scale

5. Subjects with the Minor Test* considered positive from grade 3 to 5 on the Minor test sweat intensity scale, showing sweat on the forehead under standardized conditions

6. Medical history and clinical examination that, in the investigator's opinion, do not prevent the subject from participating in the study or from using the proposed medication

7. Negative urinary pregnancy test at the initial visit for women of childbearing potential

8. Use of an effective contraceptive method (oral or injectable contraception, abstinence, intrauterine device, diaphragm, hysterectomy or bilateral ovariectomy, tubal attachment, condom, sponge, spermicide or partner with vasectomy) throughout the study for women of childbearing potential

9. Subjects must agree not to undergo other dermatological or aesthetic treatments during the study period *The Minor test must be the last test to be done. Only the subjects who fulfill all the inclusion criteria above undergo the Minor test to check for sweating in the frontal region. The graduation considered positive for inclusion in the study will be 3 to 5.

Inclusion Criteria:

1. Pregnancy or intention to become pregnant during the study period

2. Breastfeeding

3. Botulinum toxin treatments in the last 6 months

4. Subjects participating in other clinical studies

5. Any surgical procedure performed that has affected the frontal or orbicularis muscle, previous blepharoplasty or eyebrow raising

6. Any cosmetic procedures, including fillers, or scars that may interfere with the results of the study

7. Fronto-parietal alopecia according to the Norwood-Hamilton classification

8. Neoplastic, muscular or neurological diseases

9. Use of using aminoglycoside antibiotics or penicillamines, quinine or calcium channel blockers or that they will use at any time during the study

10. Inflammatory or infectious processes at the application site

11. Evident facial asymmetry

12. History of adverse event, such as sensitivity to the components of the formula, ptosis or any other adverse event that, in the investigator's opinion, prevents the research subject from participating in the study

13. Myasthenia Gravis, Eaton-Lambert Syndrome and motor neuron disease

14. Coagulation disorders or use of anticoagulants

15. Autoimmune disease

16. History of poor adherence to treatments or who have shown lack of cooperation to adhere to the study protocol

17. Any condition that, in the investigator's opinion, could compromise the results of the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brazilian Center for Studies in Dermatology	Porto Alegre	RS	Brazil	90550-141

Sponsors and Collaborators

• Brazilan Center for Studies in Dermatology

Investigators

• Principal Investigator: Doris M Hexsel, MD, Brazilian Center for Studies in Dermatology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Doris Hexsel, MD, Brazilan Center for Studies in Dermatology
• ClinicalTrials.gov Identifier: NCT01732809
• Other Study ID Numbers: 11-2011
• First Posted: Nov 26, 2012
• Last Update Posted: Dec 17, 2020
• Last Verified: Nov 1, 2020

• Keywords provided by Doris Hexsel, MD, Brazilan Center for Studies in Dermatology: wrinkles; botulinum toxin; abobotulinumtoxinA; onabotulinumtoxinA; field of anhydrotic effects
• Additional relevant MeSH terms: Botulinum Toxins, Type A; abobotulinumtoxinA

Study Results

Participant Flow

Arm/Group Title	Group A	Group B
Arm/Group Description	Patients received 2U/0.02mL of reconstituted abobotulinumtoxinA on the right side of the forehead and 2U/0.02mL of reconstituted onabotulinumtoxinA on the left side.	Patients received 2U/0.02mL of reconstituted abobotulinumtoxinA on the left side of the forehead and 2U/0.02mL of reconstituted onabotulinumtoxinA on the right side.
Period Title: Overall Study
STARTED	9	10
COMPLETED	9	9
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Group A	Group B	Total
Arm/Group Description	Patients received 2U/0.02mL of reconstituted abobotulinumtoxinA on the right side of the forehead and 2U/0.02mL of reconstituted onabotulinumtoxinA on the left side.	Patients received 2U/0.02mL of reconstituted abobotulinumtoxinA on the left side of the forehead and 2U/0.02mL of reconstituted onabotulinumtoxinA on the right side.	Total of all reporting groups
Overall Participants	9	10	19
Overall Sides of the forehead	18	20	38
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.7 (10.6)	35.7 (9.1)	39.0 (10.2)
Sex: Female, Male (Count of Participants)
Female	9 100%	10 100%	19 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	9 100%	10 100%	19 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Brazil	9 100%	10 100%	19 100%

Outcome Measures

1. Primary Outcome

Title	Horizontal Diameter of the Fields of Anhidrotic Effect
Description	The Horizontal Diameter of the Fields of Anhidrotic Effect were measured with Mirror Medical Imaging Software (Canfield Scientific, Inc., Parsippany, NJ) The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The reaction of iodine and starch with the sweat (Minor's test) allows visualizing the field of anhidrotic effects and measuring them. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FAE are observed at baseline.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

Per protocol.

Arm/Group Title	Abobotulinumtoxin A	Onabotulinumtoxin A
Arm/Group Description	Patients were randomized to the side of the forehead (left or right) in which the products were administered.	Patients were randomized to the side of the forehead (left or right) in which the products were administered.
Measure Participants	18	18
Mean (Standard Deviation) [centimeters]	0.84 (0.14)	1.24 (0.24)

2. Primary Outcome

Title	Vertical Diameter of the Fields of Anhidrotic Effect
Description	The Vertical Diameter of the Fields of Anhidrotic Effect were measured with Mirror Medical Imaging Software (Canfield Scientific, Inc., Parsippany, NJ) The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The reaction of iodine and starch with the sweat (Minor's test) allows visualizing the field of anhidrotic effects and measuring them. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FAE are observed at baseline.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	Abobotulinumtoxin A	Onabotulinumtoxin A
Arm/Group Description	Patients were randomized to the side of the forehead (left or right) in which the products were administered.	Patients were randomized to the side of the forehead (left or right) in which the products were administered.
Measure Participants	18	18
Mean (Standard Deviation) [centimeters]	1.19 (0.19)	1.50 (0.26)

3. Primary Outcome

Title	Area of the Fields of Anhidrotic Effect
Description	The area of the Fields of Anhidrotic Effect were measured with Mirror Medical Imaging Software (Canfield Scientific, Inc., Parsippany, NJ) The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The reaction of iodine and starch with the sweat (Minor's test) allows visualizing the field of anhidrotic effects and measuring them. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FAE are observed at baseline.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

Per protocol.

Arm/Group Title	Abobotulinumtoxin A	Onabotulinumtoxin A
Arm/Group Description	Patients were randomized to the side of the forehead (left or right) in which the products were administered.	Patients were randomized to the side of the forehead (left or right) in which the products were administered.
Measure Participants	18	18
Mean (Standard Deviation) [centimeters squared]	0.86 (0.22)	1.49 (0.49)

4. Secondary Outcome

Title	Wrinkle Severity Scale (WSS) at Maximum Contraction
Description	It is a 4-point validated scale for forehead lines: 0 - None - Mild - Moderate - Severe The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The muscular effect reduction can be observed by the reduction of facial lines. Wrinkle scales are used to grade the muscular effects of botulinum toxin. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FME are observed at baseline.
Time Frame	Baseline and 28 days

Outcome Measure Data

Analysis Population Description

Per protocol.

Arm/Group Title	Abobotulinumtoxin A	Onabotulinumtoxin A
Arm/Group Description	Patients were randomized to the side of the forehead (left or right) in which the products were administered.	Patients were randomized to the side of the forehead (left or right) in which the products were administered.
Measure Participants	18	18
Baseline - Grade 0	0 0%	0 0%
Baseline - Grade 1	0 0%	0 0%
Baseline - Grade 2	7 77.8%	6 60%
Baseline - Grade 3	11 122.2%	12 120%
At 28 days - Grade 0	5 55.6%	6 60%
At 28 days - Grade 1	10 111.1%	8 80%
At 28 days - Grade 2	2 22.2%	3 30%
At 28 days - Grade 3	1 11.1%	1 10%

5. Secondary Outcome

Title	Wrinkle Severity Scale (WSS) at Rest
Description	It its a 4-point validated scale for forehead lines: 0 - None - Mild - Moderate - Severe The injection of botulinum toxin type A causes both muscle paralysis and anhydrosis on sweat glands activity. The size of the muscular and anhydrotic effects are called field of anhidrotic effects (FAE) and field of muscular effects (FME). The muscular effect reduction can be observed by the reduction of facial lines. Wrinkle scales are used to grade the muscular effects of botulinum toxin. The peak effect of botulinum toxin type A occurs between 15 and 30 days after injection. There is no change from the baseline, because no FME are observed at baseline.
Time Frame	Baseline and 28 days

Outcome Measure Data

Analysis Population Description

Per protocol.

Arm/Group Title	Abobotulinumtoxin A	Onabotulinumtoxin A
Arm/Group Description	Patients were randomized to the side of the forehead (left or right) in which the products were administered.	Patients were randomized to the side of the forehead (left or right) in which the products were administered.
Measure Participants	18	18
Baseline - Grade 0	1 11.1%	1 10%
Baseline - Grade 1	8 88.9%	7 70%
Baseline - Grade 2	4 44.4%	5 50%
Baseline - Grade 3	5 55.6%	5 50%
At 28 days - Grade 0	10 111.1%	10 100%
At 28 days - Grade 1	6 66.7%	6 60%
At 28 days - Grade 2	2 22.2%	2 20%
At 28 days - Grade 3	0 0%	0 0%

6. Secondary Outcome

Title	Evoked Compound Muscle Action Potentials (ECMAP)
Description	Amplitude of the evoked compound muscle action potentials in the frontalis muscle on stimulation of the facial nerve performed at baseline and visit 2 using surface electrodes on the forehead and electrical stimulation of the facial nerve according to standard neurophysiologic procedures. The amplitude of the ECMAP was performed by an experienced neurologist using an electromyography device (Teca Sapphire; Teca Corp).
Time Frame	Baseline and 28 days

Outcome Measure Data

Analysis Population Description

Per protocol.

Arm/Group Title	Abobotulinumtoxin A	Onabotulinumtoxin A
Arm/Group Description	Patients were randomized to the side of the forehead (left or right) in which the products were administered.	Patients were randomized to the side of the forehead (left or right) in which the products were administered.
Measure Participants	18	18
Baseline	1108.17 (364.76)	1079.11 (266.02)
Day 28	202.89 (258.44)	165.39 (232.10)

Adverse Events

Time Frame	28 days
Arm/Group Title	Abobotulinumtoxin A		Onabotulinumtoxin A
Arm/Group Description	Patients were randomized to the side of the forehead (left or right) in which the products were administered.		Patients were randomized to the side of the forehead (left or right) in which the products were administered.
All Cause Mortality
	Abobotulinumtoxin A		Onabotulinumtoxin A
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Abobotulinumtoxin A		Onabotulinumtoxin A
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	Abobotulinumtoxin A		Onabotulinumtoxin A
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/19 (10.5%)		1/19 (5.3%)
Skin and subcutaneous tissue disorders
Erythema	1/19 (5.3%)	1	1/19 (5.3%)	1
Bleeding	2/19 (10.5%)	2	1/19 (5.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.