Correction of Moderate to Severe Nasolabial Folds
Conditions
Brief summary
Demonstrate the effectiveness of Belotero Balance with lidocaine (Test group) for the reduction of injection-related pain in comparison to Belotero Balance without lidocaine (Control group) for the correction of NLFs. Identify and describe adverse events (AEs) and serious adverse events (SAEs) during the course of the study. Additionally, common treatment site responses (CTRs) will be assessed.
Interventions
DEVICEBelotero® Balance with integral lidocaine
Mode of application: intradermal injection. Maximum treatment volume: 3 mL per nasolabial fold over two Treatment sessions.
DEVICEBelotero® Balance
Mode of application: intradermal injection. Maximum treatment volume: 3 mL per nasolabial fold over two Treatment sessions.
Sponsors
Merz North America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Has right and left NLF ratings of 2 or 3 (moderate or severe) on the Merz NLF Scale, as determined by the blinded evaluator. 2. Has the same Merz NLF Scale rating on both NLFs (i.e., symmetrical NLFs). 3. Is at least 18 years of age. 4. Understands and accepts the obligation not to receive any other procedures (i.e., dermal fillers, toxin treatments, facial ablative or fractional laser, microderm abrasion, chemical peels, non-invasive skin-tightening \[e.g., Ultherapy, Thermage\], or surgical procedures) below the orbital rim on the face during study participation.
Exclusion criteria
1. Had prior surgery in the mid- and/or lower-face area, including the nasolabial fold(s), or has a permanent implant or graft in the mid- and/or lower-face area that could interfere with effectiveness assessments. (NOTE: Rhinoplasty is permitted if the procedure was ≥ 12 months prior to study enrollment.) 2. Has skin or fat atrophy, beyond typical for the subject's age, in the mid- to lower-facial region or has been diagnosed with a connective tissue disorder. 3. Has unphysiological skin laxity or sun damage, beyond typical for the subject's age, or subject plans to tan during the study period. 4. Has undergone oral surgery (e.g., orthodontia, extraction, implants) in the past 30 days or plans to receive such surgery during participation in the study. 5. Has received mid- and/or lower-facial region treatments with porcine-based collagen fillers, Belotero® Volume, JUVÉDERM VOLUMA®, Restylane® Lyft, RADIESSE®, poly L-lactic acid (PLLA), or mesotherapy within the past 24 months and/or with other hyaluronic acid (HA) products within the past 12 months or plans to receive such treatment during participation in the study. 6. Has ever been treated with fat injections or permanent and/or semi-permanent dermal fillers in the mid- and/or lower-facial region or plans to receive such treatment during participation in the study. 7. Has received immunosuppressive medications or systemic steroids (except intranasal/inhaled steroids) in the past 2 months or plans to receive such treatment during participation in the study. 8. Has an acute inflammatory process or infection at the injection site (e.g., skin eruptions such as cold sores, cysts, pimples, acne, eczema, hives, streptococcus infections) or history of chronic or recurrent infection or inflammation with the potential to interfere with study results or increase the risk of AEs. 9. Has a history of allergic/anaphylactic reactions, including hypersensitivity to lidocaine or anesthetics of the amide type, hyaluronic acid preparations, gram positive bacterial proteins, or any of the device components. 10. Has a known bleeding disorder or has received or is planning to receive anti-coagulation, anti-platelet, or thrombolytic medications (e.g., warfarin), anti-inflammatory drugs (oral/injectable corticosteroids or NSAIDs \[e.g., aspirin, ibuprofen\]), or other substances known to increase coagulation time (e.g., vitamins or herbal supplements, i.e., Vitamin E, garlic, gingko) from 10 days before injection to 3 days after injection. 11. Has any other medical condition with the potential to interfere with study outcome assessments or compromise subject safety (i.e., increase the risk of adverse events).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Pain Using Visual Analog Scale (VAS) | Day 1 | Pain was assessed using a using a 10 centimeter (cm) VAS. It included 21-numbered circles at 0.5 cm increments, spanning 10 cm total, and was anchored by word descriptors. The VAS scores ranged from 0 (no pain) to 10 (very severe pain).The level of pain was evaluated for each NLF independently immediately upon completion of injection (time zero) on Day 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Responders With Greater Than or Equal to (>=) 1-point Improvement as Evaluated Using Merz NLF Scale at Week 6 | Week 6 | The Merz NLF scale was used to measure the aesthetic effectiveness of the study products. Each NLF was assessed separately. The Merz NLF scale is a 5-grade scale ranging from 0 (no folds) to 4 (very severe folds). Response was defined \>=1-point improvement on the Merz NLF Scale for each NLF compared to baseline. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Baseline up to Week 6 | — |
| Number of Participants With Incidence of Any Common Treatment Site Response (CTR) Evaluated Using Participant Diaries | Baseline up to Week 6 | CTR were evaluated using participant diaries. Participants recorded daily in the diary any pre-defined CTR that occurred. These CTR included swelling, firmness, lumps/bumps, bruising, pain, tenderness upon pressing, redness, discoloration (not redness or bruising), itching, stinging/burning, and numbness. |
| Number of Participants With Incidence of Any CTR by Severity Evaluated Using Participant Diaries | Baseline up to Week 6 | CTR were evaluated using participant diaries. Participants recorded daily in the diary any pre-defined CTR that occurred. These CTR included swelling, firmness, lumps/bumps, bruising, pain, tenderness upon pressing, redness, discoloration (not redness or bruising), itching, stinging/burning, and numbness. |
| Number of Participants With Incidence of Any CTR by Duration Evaluated Using Participant Diaries | Baseline up to Week 6 | CTR were evaluated using participant diaries. Participants recorded daily in the diary any pre-defined CTR that occurred. These CTR included swelling, firmness, lumps/bumps, bruising, pain, tenderness upon pressing, redness, discoloration (not redness or bruising), itching, stinging/burning, and numbness. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 3 investigative sites in the United States.
Pre-assignment details
A total of 65 participants were screened, out of which 52 participants were randomized and treated. Of these, 51 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Belotero Balance With or Without Lidocaine Participants received treatment with Test Product BBL, injection, in one of the two NLF and Control Product BB without lidocaine, injection, in the contralateral NLF on Day 1. The BBL and BB injections were given in the alar-targus line to the oral commissure. The maximum treatment volume was 3 mL per NLF over two treatment sessions, on Day 1 and optional touch-up at Week 2. Participants who were eligible for an optional touch-up treatment to achieve optimal correction based on investigator's discretion received the BBL and BB injections on Week 2. | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Belotero Balance With or Without Lidocaine |
|---|---|
| Age, Continuous | 58.4 years STANDARD_DEVIATION 10.2 |
| Fitzpatrick Skin Type Skin Type I | 1 Participants |
| Fitzpatrick Skin Type Skin Type II | 20 Participants |
| Fitzpatrick Skin Type Skin Type III | 15 Participants |
| Fitzpatrick Skin Type Skin Type IV | 4 Participants |
| Fitzpatrick Skin Type Skin Type V | 5 Participants |
| Fitzpatrick Skin Type Skin Type VI | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 16 Participants |
| Race/Ethnicity, Customized Caucasian | 36 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic and not Latino | 51 Participants |
| Region of Enrollment United States | 52 Participants |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 52 |
| other Total, other adverse events | 5 / 52 |
| serious Total, serious adverse events | 0 / 52 |
Outcome results
Primary
Mean Pain Using Visual Analog Scale (VAS)
Pain was assessed using a using a 10 centimeter (cm) VAS. It included 21-numbered circles at 0.5 cm increments, spanning 10 cm total, and was anchored by word descriptors. The VAS scores ranged from 0 (no pain) to 10 (very severe pain).The level of pain was evaluated for each NLF independently immediately upon completion of injection (time zero) on Day 1.
Time frame: Day 1
Population: The full analysis set (FAS) included all randomized participants and were analyzed as randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product: BBL | Mean Pain Using Visual Analog Scale (VAS) | 3.07 score on a scale | Standard Deviation 1.88 |
| Control Product: BB | Mean Pain Using Visual Analog Scale (VAS) | 5.94 score on a scale | Standard Deviation 2.41 |
p-value: <0.000195% CI: [-3.42, -2.33]t-test, 2 sided
Secondary
Number of Participants With Incidence of Any Common Treatment Site Response (CTR) Evaluated Using Participant Diaries
CTR were evaluated using participant diaries. Participants recorded daily in the diary any pre-defined CTR that occurred. These CTR included swelling, firmness, lumps/bumps, bruising, pain, tenderness upon pressing, redness, discoloration (not redness or bruising), itching, stinging/burning, and numbness.
Time frame: Baseline up to Week 6
Population: The SES included all participants who were enrolled into the study, randomized, and received an injection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Test Product: BBL | Number of Participants With Incidence of Any Common Treatment Site Response (CTR) Evaluated Using Participant Diaries | 41 participants |
| Control Product: BB | Number of Participants With Incidence of Any Common Treatment Site Response (CTR) Evaluated Using Participant Diaries | 45 participants |
Secondary
Number of Participants With Incidence of Any CTR by Duration Evaluated Using Participant Diaries
CTR were evaluated using participant diaries. Participants recorded daily in the diary any pre-defined CTR that occurred. These CTR included swelling, firmness, lumps/bumps, bruising, pain, tenderness upon pressing, redness, discoloration (not redness or bruising), itching, stinging/burning, and numbness.
Time frame: Baseline up to Week 6
Population: The SES included all participants who were enrolled into the study, randomized, and received an injection. Participants who were evaluable for this measure at given time period were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Test Product: BBL | Number of Participants With Incidence of Any CTR by Duration Evaluated Using Participant Diaries | 4 to 7 days | 14 participants |
| Test Product: BBL | Number of Participants With Incidence of Any CTR by Duration Evaluated Using Participant Diaries | 15 to 30 days | 3 participants |
| Test Product: BBL | Number of Participants With Incidence of Any CTR by Duration Evaluated Using Participant Diaries | 8 to 17 days | 8 participants |
| Test Product: BBL | Number of Participants With Incidence of Any CTR by Duration Evaluated Using Participant Diaries | Greater than (>) 30 days | 0 participants |
| Test Product: BBL | Number of Participants With Incidence of Any CTR by Duration Evaluated Using Participant Diaries | 1 to 3 days | 16 participants |
| Control Product: BB | Number of Participants With Incidence of Any CTR by Duration Evaluated Using Participant Diaries | Greater than (>) 30 days | 0 participants |
| Control Product: BB | Number of Participants With Incidence of Any CTR by Duration Evaluated Using Participant Diaries | 1 to 3 days | 20 participants |
| Control Product: BB | Number of Participants With Incidence of Any CTR by Duration Evaluated Using Participant Diaries | 4 to 7 days | 14 participants |
| Control Product: BB | Number of Participants With Incidence of Any CTR by Duration Evaluated Using Participant Diaries | 8 to 17 days | 9 participants |
| Control Product: BB | Number of Participants With Incidence of Any CTR by Duration Evaluated Using Participant Diaries | 15 to 30 days | 2 participants |
Secondary
Number of Participants With Incidence of Any CTR by Severity Evaluated Using Participant Diaries
CTR were evaluated using participant diaries. Participants recorded daily in the diary any pre-defined CTR that occurred. These CTR included swelling, firmness, lumps/bumps, bruising, pain, tenderness upon pressing, redness, discoloration (not redness or bruising), itching, stinging/burning, and numbness.
Time frame: Baseline up to Week 6
Population: The SES included all participants who were enrolled into the study, randomized, and received an injection. Participants who were evaluable for this measure at given time period were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Test Product: BBL | Number of Participants With Incidence of Any CTR by Severity Evaluated Using Participant Diaries | Mild | 23 participants |
| Test Product: BBL | Number of Participants With Incidence of Any CTR by Severity Evaluated Using Participant Diaries | Moderate | 14 participants |
| Test Product: BBL | Number of Participants With Incidence of Any CTR by Severity Evaluated Using Participant Diaries | Severe | 4 participants |
| Control Product: BB | Number of Participants With Incidence of Any CTR by Severity Evaluated Using Participant Diaries | Mild | 24 participants |
| Control Product: BB | Number of Participants With Incidence of Any CTR by Severity Evaluated Using Participant Diaries | Moderate | 18 participants |
| Control Product: BB | Number of Participants With Incidence of Any CTR by Severity Evaluated Using Participant Diaries | Severe | 3 participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Baseline up to Week 6
Population: The SES included all participants who were enrolled into the study, randomized, and received an injection.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Test Product: BBL | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 5 participants |
| Test Product: BBL | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
Secondary
Percentage of Responders With Greater Than or Equal to (>=) 1-point Improvement as Evaluated Using Merz NLF Scale at Week 6
The Merz NLF scale was used to measure the aesthetic effectiveness of the study products. Each NLF was assessed separately. The Merz NLF scale is a 5-grade scale ranging from 0 (no folds) to 4 (very severe folds). Response was defined \>=1-point improvement on the Merz NLF Scale for each NLF compared to baseline.
Time frame: Week 6
Population: The FAS included all randomized participants and was analyzed as randomized. Participants who were evaluable for this measure at given time period were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Test Product: BBL | Percentage of Responders With Greater Than or Equal to (>=) 1-point Improvement as Evaluated Using Merz NLF Scale at Week 6 | 51.0 percentage of participants |
| Control Product: BB | Percentage of Responders With Greater Than or Equal to (>=) 1-point Improvement as Evaluated Using Merz NLF Scale at Week 6 | 52.9 percentage of participants |