Multicenter Study of the Safety and Effectiveness of Dermal Filler, Belotero®.
Condition: Facial Wrinkles
MeSH terms: Facies
Intervention: Belotero; Zyplast
Intervention description: 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.; 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.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 118.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Facial wrinkles; Nasolabial fold

Summary:

      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.
    

Eligibility criteria:

        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.