Facial Wrinkles
Conditions
Keywords
Facial wrinkles, Nasolabial fold
Brief 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.
Interventions
DEVICEBelotero
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.
DEVICEZyplast
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.
Sponsors
Merz North America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Baseline and Week 12 of follow-up | 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. |
Countries
United States
Participant flow
Recruitment details
The subjects in this trial were enrolled from six study centers in the United States between November 2006 and July 2007. Subjects were males or non-pregnant females aged 18 to 75 years and who had bilateral nasolabial folds with a severity of 2 or 3 (moderate to severe).
Pre-assignment details
The planned enrollment was 120 subjects; 118 subjects were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study | 118 |
| Total | 118 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | Miscellaneous reasons | 4 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 110 Participants |
| Age Continuous | 52.4 years STANDARD_DEVIATION 9.5 |
| Sex: Female, Male Female | 109 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 108 / 118 | 109 / 118 |
| serious Total, serious adverse events | 0 / 118 | 0 / 118 |
Outcome results
Primary
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.
Time frame: Baseline and Week 12 of follow-up
Population: The Full Analysis Set (FAS) population was the analysis population which was defined as all subjects who were randomized and received at least one injection of the study device to the nasolabial folds.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Belotero | 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. | 1.224 Wrinkle Severity Rating Score (SRS) | Standard Error 0.111 |
| Zyplast | 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. | 1.176 Wrinkle Severity Rating Score (SRS) | Standard Error 0.111 |
Comparison: The null, H0, and the alternative hypothesis, H1, are as follows:~H0(1): adjusted mean(dadj\[i\]) ≤ -Δ versus H1(1): adjusted mean(dadj\[i\]) \> -Δ H0(2): adjusted mean(dadj\[i\]) ≤ 0 versus H1(2): adjusted mean(dadj\[i\]) \> 0 The sample size calculation was based on the following assumptions: Type I error α = 0.025 (one sided); Power = 90%; Non-inferiority margin Δ = 0.25; Estimated common standard deviation (SD) = 0.75. Under these assumptions, a total of 100 evaluable subjects were needed.p-value: 0.73395% CI: [-0.228, 0.323]ANCOVA