Multicenter Study of the Safety and Effectiveness of Dermal Filler, Belotero®.

A Randomized, Blinded, Controlled, Multicenter Study of the Safety and Effectiveness of Dermal Filler, Belotero®, After Mid-to-Deep Dermal Implantation for Correction of Moderate to Severe Facial Wrinkles

This was a study to find out how an investigational product, Belotero, compares to a second product in people with facial wrinkles, such as nasolabial folds. Nasolabial folds are wrinkles on the face that go from the outside of the nostrils to the edges of the mouth. Additionally, this study determined Belotero is safe and tolerable and corrects facial wrinkles, such as nasolabial folds.

Study Overview

• Status: Completed
• Conditions: Facial Wrinkles
• Intervention / Treatment: Device: Belotero; Device: Zyplast

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Total Skin And Beauty Dermatology Center
  • California
    • Los Angeles, California, United States, 90069
      • Skin Care & Laser Physicians of Beverly Hills
    • San Francisco, California, United States, 94115
      • Maas Clinic
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Savin Dermatology
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • William Coleman, III, MD
  • New York
    • White Plains, New York, United States, 10604
      • Dermatology Surgery and Laser Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects reviewed and signed a statement of Informed Consent and a HIPAA authorization prior to initiating any study-specific procedures. In addition, subjects were asked to provide a separate release for use of their photographs in publications. Subjects could refuse the photo release without jeopardizing their eligibility to participate in the study.
2. Subjects were 18 - 75 years of age, and of any race or sex.
3. Female subjects were postmenopausal for at least 1 year, had a hysterectomy, or had a tubal ligation; or, if of childbearing potential, agreed to use an approved method of birth control throughout the study (i.e., oral/systemic contraceptives, intrauterine device [IUD], or spermicide in combination with a barrier method of contraception), were abstinent, or were in a monogamous relationship with a vasectomized partner; and had a negative urine pregnancy test at the screening visit.
4. Subjects had bilateral nasolabial folds with a severity score of 2 or 3 on the wrinkle SRS assessed by the blinded evaluator.
5. Each subject had an adequate understanding of the language (spoken and written English or Spanish) and was willing to comply with the study requirements.

Exclusion Criteria:

1. A personal history of allergic/anaphylactic reactions including hypersensitivity to local anesthetics (eg, lidocaine, etc), HA preparations, and/or gram-positive bacterial protein.
2. A known history of keloids or bleeding disorders.
3. An active inflammatory process in the nasolabial fold area (skin eruptions such as cysts, pimples, rashes, cancerous/pre-cancerous lesions, psoriasis, neurodermatitis, or any other active skin disease) or severe scarring that might interfere with study assessments.
4. Women who were pregnant, planning to become pregnant during the study, or who were breast-feeding.
5. Subjects who planned to undergo major facial surgery during the course of the study (eg, rhinoplasty [with or without implant], facelift, congenital defect repair, etc).
6. Subjects with clinically important disease, as judged by the investigator, within 3 months of the study (eg, significant laboratory test abnormalities, myocardial infarct, stroke, cancer, connective tissue diseases [scleroderma, systemic lupus erythematous], systemic infection, uncontrolled diabetes, etc.), including those with medical conditions that might require the use of immunosuppressive medications during the trial (eg, severe, uncontrolled asthma, rheumatoid arthritis, autoimmune diseases, etc).
7. Severe physical, neurological or mental disease.
8. Excessive facial hair that might interfere with the evaluation of the wrinkle assessments.
9. Any systemic or dermatologic disorder, which, in the opinion of the investigator,would interfere with the study results or increase the risk of adverse events (AEs).
10. Subjects who had used exclusionary medications/treatments.
11. Participation in a clinical investigation within the 30 days prior to the first planned device administration or during this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Belotero	Device: Belotero; Belotero, injectable hyaluronic acid gel device, implanted into the nasolabial fold in the Treatment Phase of the study (multiple injections of 0.1 to 0.2 mL, up to a maximum of 3 mL over 2 treatment sessions). Dose was based on the severity of the wrinkle, with a maximum dose to achieve 100% correction to be administered.
ACTIVE_COMPARATOR: Zyplast	Device: Zyplast; Zyplast Collagen Implant, an injectable dermal collagen device, implanted into the nasolabial fold in the Treatment Phase of the study (average injection of 1.0 mL). Dose was based on the severity of the wrinkle, with a maximum dose to achieve 100% correction to be administered. Zyplast was obtained by each site from commercially available supplies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted (LS) Mean Change From Baseline in Wrinkle Severity Rating Scale (SRS) Score of Each Nasolabial Fold (NLF) as Determined by the Blinded Evaluator at Week 12.	The severity of the nasolabial folds was measured using the wrinkle Severity Rating Scale (SRS), where 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Extreme, which is an ordinal scale.	Baseline and Week 12 of follow-up

Collaborators and Investigators

• Sponsor: Merz North America, Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (ACTUAL): July 1, 2007
• Study Completion (ACTUAL): December 1, 2008

Study Registration Dates

• First Submitted: April 3, 2009
• First Submitted That Met QC Criteria: April 3, 2009
• First Posted (ESTIMATE): April 6, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): April 26, 2013
• Last Update Submitted That Met QC Criteria: April 19, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Facial wrinkles; Nasolabial fold
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Facies
• Other Study ID Numbers: MUS 90028-0622/1