Safety Study of DWP-450 (Botulinum Toxin, Type a) to Treat Glabellar Lines - EV-006

• Sponsor: Evolus, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02428608
• Collaborator: PPD (Industry)
• Enrollment: 570
• Location: 1
• Arm: 1
• Duration (Months): 18.1
• Patients Per Site Per Month: 31.5

Study Details

Study Description

Brief Summary

The primary objective is to demonstrate the safety of multiple doses of DWP-450 purified Botulinum neurotoxin, Type A, in treatment of moderate to severe glabellar lines associated with corrugator and procerus muscle activity in adult subjects.

Condition or Disease	Intervention/Treatment	Phase
Glabellar Frown Lines	Biological: DWP-450 (Botulinum purified neurotoxin, Type A)	Phase 2

Detailed Description

Up to five hundred and thirty (530) subjects will be enrolled and injected with the study drug DWP-450 over the course of the 365 day study.

Subjects with moderate-to-severe glabellar lines at maximum frown on the 4 point Glabellar Line Scale (GLS, 0=none, 1= mild, 2=moderate, 3=severe), as judged by the investigator, will be eligible for injection with DWP-450.

Subjects may receive up to a maximum of 4 treatments and will be followed for 365 days from initial treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 570 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: This is an open label safety study
• Primary Purpose: Treatment
• Official Title: A Multi-center, Open Label, Single Dose, Phase II Trial to Demonstrate the Safety of DWP-450 in Adult Subjects for Treatment of Moderate-to-severe Glabellar Lines
• Study Start Date: May 1, 2015
• Actual Primary Completion Date: Oct 1, 2016
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Botulinum toxin, Tyoe A DWP-450 (Botulinum toxin, Type A)	Biological: DWP-450 (Botulinum purified neurotoxin, Type A); Botulinum toxin, Type A; Other Names: DWP-450

Outcome Measures

Primary Outcome Measures

1. The Safety of Repeat DWP-450 Treatments - Proportion of Subjects With at Least One Adverse Event Over 1 Year [365 days]

   The primary safety analysis was the calculation of the proportion of subjects with at least one adverse event that occurred from Day 0 through Day 365.

Other Outcome Measures

1. Change From Baseline Glabellar Line Scale (GLS) Score at Rest and at Maximum Frown [365 days]

   Proportion of subjects with an improvement of 1 point or more (i.e., ≥1 point responders) on the GLS at rest at end of study/early termination: by Investigator assessment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subjects must be an adult 18 years of age and over

• Subject is able to provide informed consent and comply with study instructions

• Subject has moderate-to-severe glabellar lines on maximum frown as assessed by the investigator and subject using the GLS

• Subject is willing and able to complete the entire course of the study

Exclusion Criteria:

• Previous treatment with botulinum toxin of any serotype in any area within the last 6 months

• Previous treatment with any facial aesthetic procedure (e.g. injection with fillers, chemical peeling, photo rejuvenation) in the glabellar area within the last 12 months

• Previous insertion of permanent material in the glabellar area

• Planned treatment with botulinum toxin of any serotype in any other body region during the study period

• Any surgery in the glabellar area including surgical removal of the corrugator, procerus, or depressor supercilii muscles or a combination of these, or scars in the glabellar area and the surrounding areas (including eye brow)

• Energy based or cryo-therapy based treatment of facial muscles superior to the lateral canthus

• Any other planned facial aesthetic procedure during the trial period, superior to the level of the lateral canthus (subjects can continue with their usual skin care routine)

• Inability to substantially lessen glabellar frown lines even by physically spreading them apart

• Marked facial asymmetry

• Ptosis of eyelid and/or eyebrow, or history of eyelid and/or eyebrow ptosis

• History of facial nerve palsy

• Excessive dermatochalasis, deep dermal scarring, thick sebaceous skin

• Any active infection in the area of the injection sites

• Medical condition that may affect neuromuscular function (e.g., myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis)

• Evidence of recent alcohol or drug abuse

• Medical or psychiatric conditions that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study

• Pregnant, nursing or sexually active female subjects who are of childbearing potential and who are not willing to use an acceptable form of contraception

• Known allergy or hypersensitivity to botulinum toxin preparation

• Participation in another interventional clinical study within the last 30 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Advanced Skin Research Center at Skin Specialists, PC	Omaha	Nebraska	United States	68144

Sponsors and Collaborators

• Evolus, Inc.
• PPD

Investigators

• Study Director: Rui Avelar, MD, Evolus, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Evolus, Inc.
• ClinicalTrials.gov Identifier: NCT02428608
• Other Study ID Numbers: Evolus - CLIN006
• First Posted: Apr 29, 2015
• Last Update Posted: Apr 24, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Evolus, Inc.: Glabellar Lines; Botulinum toxin, Type A
• Additional relevant MeSH terms: Botulinum Toxins, Type A

Study Results

Participant Flow

Arm/Group Title	Botulinum Toxin, Tyoe A
Arm/Group Description	DWP-450 (Botulinum toxin, Type A) DWP-450 (Botulinum purified neurotoxin, Type A): Botulinum toxin, Type A
Period Title: Overall Study
STARTED	570
COMPLETED	487
NOT COMPLETED	83

Baseline Characteristics

Arm/Group Title	Botulinum Toxin, Type A
Arm/Group Description	DWP-450 (Botulinum toxin, Type A) DWP-450 (Botulinum purified neurotoxin, Type A): Botulinum toxin, Type A
Overall Participants	570
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	519 91.1%
>=65 years	51 8.9%
Sex: Female, Male (Count of Participants)
Female	510 89.5%
Male	60 10.5%

Outcome Measures

1. Primary Outcome

Title	The Safety of Repeat DWP-450 Treatments - Proportion of Subjects With at Least One Adverse Event Over 1 Year
Description	The primary safety analysis was the calculation of the proportion of subjects with at least one adverse event that occurred from Day 0 through Day 365.
Time Frame	365 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Botulinum Toxin, Tyoe A
Arm/Group Description	DWP-450 (Botulinum toxin, Type A) DWP-450 (Botulinum purified neurotoxin, Type A): Botulinum toxin, Type A
Measure Participants	570
Count of Participants [Participants]	235 41.2%

2. Other Pre-specified Outcome

Title	Change From Baseline Glabellar Line Scale (GLS) Score at Rest and at Maximum Frown
Description	Proportion of subjects with an improvement of 1 point or more (i.e., ≥1 point responders) on the GLS at rest at end of study/early termination: by Investigator assessment
Time Frame	365 days

Outcome Measure Data

Analysis Population Description

By Investigator assessment, 500 subjects had a GLS score at rest >0 (i.e., 1, 2 or 3) at baseline and therefore could potentially have had a ≥1 point improvement in GLS score at rest at a post-baseline visit; 64 subjects were missing the EOS GLS assessment

Arm/Group Title	Botulinum Toxin, Type A
Arm/Group Description	DWP-450 (Botulinum toxin, Type A) DWP-450 (Botulinum purified neurotoxin, Type A): Botulinum toxin, Type A
Measure Participants	500
Count of Participants [Participants]	355 62.3%

Adverse Events

Time Frame	1 year
Arm/Group Title	Botulinum Toxin, Type A
Arm/Group Description	DWP-450 (Botulinum toxin, Type A) DWP-450 (Botulinum purified neurotoxin, Type A): Botulinum toxin, Type A
All Cause Mortality
	Botulinum Toxin, Type A
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Botulinum Toxin, Type A
	Affected / at Risk (%)	# Events
Total	7/570 (1.2%)
Gastrointestinal disorders
Small intestinal obstruction	1/570 (0.2%)	1
Colitis	1/570 (0.2%)	1
Injury, poisoning and procedural complications
Overdose	1/570 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/570 (0.2%)	1
Uterine leiomyoma	1/570 (0.2%)	1
Squamous cell carcinoma	1/570 (0.2%)	1
Nervous system disorders
Carotid artery stenosis	1/570 (0.2%)	1
Psychiatric disorders
Anxiety	1/570 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Botulinum Toxin, Type A
	Affected / at Risk (%)	# Events
Total	228/570 (40%)
Blood and lymphatic system disorders
Anemia	2/570 (0.4%)	2
Lymphadenopathy	1/570 (0.2%)	1
Thrombocytosis	2/570 (0.4%)	2
Cardiac disorders
Bradycardia	2/570 (0.4%)	2
Bundle branch block right	3/570 (0.5%)	3
Sinus arrhythmia	2/570 (0.4%)	2
Sinus bradycardia	2/570 (0.4%)	2
atrioventricular block first degree	1/570 (0.2%)	1
myocardial infarction	1/570 (0.2%)	1
supraventricular extrasystoles	1/570 (0.2%)	1
tachycardia	1/570 (0.2%)	1
Ear and labyrinth disorders
Cerumen impaction	1/570 (0.2%)	1
Tinnitus	2/570 (0.4%)	2
Vertigo	3/570 (0.5%)	3
Endocrine disorders
hypothyroidism	2/570 (0.4%)	2
Eye disorders
Blepharospasm	2/570 (0.4%)	2
Brow ptosis	3/570 (0.5%)	3
Eyelid ptosis	7/570 (1.2%)	8
Vision blurred	2/570 (0.4%)	2
blepharitis	1/570 (0.2%)	1
cataract	1/570 (0.2%)	1
chalazion	1/570 (0.2%)	1
dry eye	1/570 (0.2%)	1
eye swelling	1/570 (0.2%)	1
eyelid oedema	1/570 (0.2%)	1
eyelid sensory disorder	1/570 (0.2%)	1
ocular rosacea	1/570 (0.2%)	1
Gastrointestinal disorders
Colitis	1/570 (0.2%)	1
Dysphagia	2/570 (0.4%)	2
Gastroesophageal reflux disease	2/570 (0.4%)	2
Toothache	3/570 (0.5%)	3
abdominal discomfort	1/570 (0.2%)	1
abdominal pain	1/570 (0.2%)	1
abdominal pain upper	1/570 (0.2%)	1
diverticulum	1/570 (0.2%)	1
dyspepsia	1/570 (0.2%)	1
gastritis	1/570 (0.2%)	1
large intestine polyp	1/570 (0.2%)	1
nausea	1/570 (0.2%)	1
paraesthesia oral	1/570 (0.2%)	1
salivary gland disorder	1/570 (0.2%)	1
tooth disorder	1/570 (0.2%)	1
General disorders
Injection site bruising	2/570 (0.4%)	3
Injection site pain	3/570 (0.5%)	3
Injection site swelling	3/570 (0.5%)	3
Pyrexia	3/570 (0.5%)	5
fatigue	1/570 (0.2%)	1
injection site pruritus	1/570 (0.2%)	1
injection site reaction	1/570 (0.2%)	1
local swelling	1/570 (0.2%)	1
tenderness	1/570 (0.2%)	1
Hepatobiliary disorders
hepatic cyst	1/570 (0.2%)	1
Immune system disorders
Hypersensitivity	3/570 (0.5%)	3
Seasonal allergy	2/570 (0.4%)	2
Infections and infestations
Bronchitis	7/570 (1.2%)	7
Herpes zoster	3/570 (0.5%)	3
Hordeolum	2/570 (0.4%)	2
Influenza	5/570 (0.9%)	5
Nasopharyngitis	13/570 (2.3%)	16
Pharyngitis streptococcal	2/570 (0.4%)	2
Sinusitis	14/570 (2.5%)	15
Tooth abscess	2/570 (0.4%)	2
Upper respiratory tract infection	16/570 (2.8%)	19
Urinary tract infection	10/570 (1.8%)	10
cellulitis	1/570 (0.2%)	1
conjunctivitis	1/570 (0.2%)	1
cystitis	1/570 (0.2%)	1
diverticulitis	1/570 (0.2%)	1
ear infection	1/570 (0.2%)	1
eye infection	1/570 (0.2%)	1
folliculitis	1/570 (0.2%)	1
gastroenteritis	1/570 (0.2%)	1
genital herpes	1/570 (0.2%)	1
Helicobacter gastritis	1/570 (0.2%)	1
Herpes simplex	1/570 (0.2%)	1
oral herpes	1/570 (0.2%)	1
otitis media	1/570 (0.2%)	1
pharyngitis	1/570 (0.2%)	1
tooth infection	1/570 (0.2%)	1
vaginitis gardnerella	1/570 (0.2%)	1
viral infection	1/570 (0.2%)	1
Injury, poisoning and procedural complications
Contusion	9/570 (1.6%)	10
Foot fracture	4/570 (0.7%)	4
Hand fracture	2/570 (0.4%)	2
Ligament sprain	2/570 (0.4%)	2
Meniscus injury	2/570 (0.4%)	2
Procedural pain	4/570 (0.7%)	4
Road traffic accident	2/570 (0.4%)	2
Arthropod bite	1/570 (0.2%)	1
Concussion	1/570 (0.2%)	1
Excoriation	1/570 (0.2%)	1
Eye laser scar	1/570 (0.2%)	1
Facial bones fracture	1/570 (0.2%)	1
Fall	1/570 (0.2%)	1
Fibula fracture	1/570 (0.2%)	1
Laceration	1/570 (0.2%)	1
Limb injury	1/570 (0.2%)	1
Lower limb fracture	1/570 (0.2%)	1
Muscle strain	1/570 (0.2%)	1
Post procedural discomfort	1/570 (0.2%)	1
Rib fracture	1/570 (0.2%)	1
Sunburn	1/570 (0.2%)	1
Tendon injury	1/570 (0.2%)	1
Tibia fracture	1/570 (0.2%)	1
Wrist fracture	1/570 (0.2%)	1
Investigations
Blood creatinine increased	2/570 (0.4%)	2
electrocardiogram QT prolonged	1/570 (0.2%)	1
electrocardiogram T wave abnormal	1/570 (0.2%)	1
electrocardiogram abnormal	1/570 (0.2%)	1
intraocular pressure test	1/570 (0.2%)	1
QRS axis abnormal	1/570 (0.2%)	1
Metabolism and nutrition disorders
hypercholesterolaemia	1/570 (0.2%)	1
hyperkalaemia	1/570 (0.2%)	1
vitamin D deficiency	1/570 (0.2%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	3/570 (0.5%)	3
Back pain	4/570 (0.7%)	4
Intervertebral disc protrusion	2/570 (0.4%)	2
Muscle spasms	2/570 (0.4%)	4
Neck pain	4/570 (0.7%)	4
Pain in extremity	6/570 (1.1%)	6
Plantar fasciitis	2/570 (0.4%)	2
Trigger finger	1/570 (0.2%)	2
arthritis	1/570 (0.2%)	1
fibromyalgia	1/570 (0.2%)	1
fracture pain	1/570 (0.2%)	1
mobility decreased	1/570 (0.2%)	1
osteoarthritis	1/570 (0.2%)	1
pain in jaw	1/570 (0.2%)	1
spinal osteoarthritis	1/570 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid neoplasm	2/570 (0.4%)	2
Uterine leiomyoma	1/570 (0.2%)	1
acrochordon	1/570 (0.2%)	1
dysplastic naevus	1/570 (0.2%)	1
melanocytic naevus	1/570 (0.2%)	1
seborrhoeic keratosis	1/570 (0.2%)	1
Nervous system disorders
Headache	75/570 (13.2%)	94
Migraine	4/570 (0.7%)	6
Tension headache	2/570 (0.4%)	2
dizziness	1/570 (0.2%)	1
hypoaesthesia	1/570 (0.2%)	1
paraesthesia	1/570 (0.2%)	1
presyncope	1/570 (0.2%)	1
radiculitis cervical	1/570 (0.2%)	1
Psychiatric disorders
Anxiety	2/570 (0.4%)	2
Depression	4/570 (0.7%)	4
adjustment disorder with depressed mood	1/570 (0.2%)	1
attention deficit/hyperactivity disorder	1/570 (0.2%)	1
insomnia	1/570 (0.2%)	1
Renal and urinary disorders
nephrolithiasis	1/570 (0.2%)	1
proteinuria	1/570 (0.2%)	1
Reproductive system and breast disorders
breast tenderness	1/570 (0.2%)	1
vaginal discharge	1/570 (0.2%)	1
vaginal haemorrhage	1/570 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Cough	7/570 (1.2%)	7
Oropharyngeal pain	2/570 (0.4%)	2
asthma	1/570 (0.2%)	1
nasal congestion	1/570 (0.2%)	1
pulmonary mass	1/570 (0.2%)	1
sinus congestion	1/570 (0.2%)	1
sinus disorder	1/570 (0.2%)	1
upper-airway cough syndrome	1/570 (0.2%)	1
Skin and subcutaneous tissue disorders
Acne	6/570 (1.1%)	6
Actinic keratosis	3/570 (0.5%)	3
Dermatitis contact	6/570 (1.1%)	6
Eczema	2/570 (0.4%)	2
Pruritus	2/570 (0.4%)	3
Solar lentigo	2/570 (0.4%)	2
Dry skin	1/570 (0.2%)	1
Ecchymosis	1/570 (0.2%)	1
Erythema	1/570 (0.2%)	1
Post inflammatory pigmentation change	1/570 (0.2%)	1
Rash	1/570 (0.2%)	1
Rash papular	1/570 (0.2%)	1
Rash pruritic	1/570 (0.2%)	1
Rosacea	1/570 (0.2%)	1
Skin mass	1/570 (0.2%)	1
Skin swelling	1/570 (0.2%)	1
Social circumstances
menopause	2/570 (0.4%)	2
Vascular disorders
Hot flush	1/570 (0.2%)	1
Hypertension	10/570 (1.8%)	10

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.