Evaluation of Pain With Belotero® Balance With Integral Lidocaine for Correction of the Nasolabial Folds

Study Overview
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Brief Summary
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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.

Official Title
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Evaluation of Pain With Belotero® Balance With Integral Lidocaine for Correction of the Nasolabial Folds

Conditions
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Correction of Moderate to Severe Nasolabial Folds

Intervention / Treatment
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* Device: Belotero® Balance with integral lidocaine
* Device: Belotero® Balance


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has right and left NLF ratings of 2 or 3 (moderate or severe) on the Merz NLF Scale, as determined by the blinded evaluator. Has the same Merz NLF Scale rating on both NLFs (i.e., symmetrical NLFs). Is at least 18 years of age. 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: 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.) 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. Has unphysiological skin laxity or sun damage, beyond typical for the subject's age, or subject plans to tan during the study period. 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. 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. 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. 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. 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. 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. 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. 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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Belotero® Balance with integral lidocaine<br>Belotero® Balance with integral lidocaine will be injected in one of the two NLF (split-face study design: treatment side will be randomized) | Device: Belotero® Balance with integral lidocaine<br>* Mode of application: intradermal injection. Maximum treatment volume: 3 mL per nasolabial fold over two Treatment sessions.<br>* Other names: Hyaluronic acid dermal filler with lidocaine, single use syringe;|
| Active Comparator: Belotero Balance without lidocaine<br>Belotero Balance without lidocaine will be injected in one of the two NLF (split-face study design: treatment side will be randomized) | Device: Belotero® Balance<br>* Mode of application: intradermal injection. Maximum treatment volume: 3 mL per nasolabial fold over two Treatment sessions.<br>* Other names: Hyaluronic acid dermal filler, single use syringe;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 6 | 
| 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 | 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. | Baseline up to Week 6 | 
| 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. | Baseline up to Week 6 | 
| 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. | Baseline up to Week 6 |