Evaluation of Pain With Belotero® Balance With Integral L... | NCT03319719

NCT03319719

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Belotero® Balance with integral lidocaine	Experimental	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
Belotero Balance without lidocaine	Active Comparator	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

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Belotero® Balance with integral lidocaine	Device	Mode of application: intradermal injection. Maximum treatment volume: 3 mL per nasolabial fold over two Treatment sessions.	Belotero® Balance with integral lidocaine

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Eligibility Module

Eligibility Criteria

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).

Contacts/Locations Module

Name	Affiliation	Role
Peter Kreymerman, MD, FACS	Merz North America, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Center for Dermatology and Dermatology Surgery; Merz Investigational Site #0010170		Washington D.C.	District of Columbia	20037	United States

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Belotero Balance With or Without Lidocaine	Participants received treatment with Test Product belotero balance with lidocaine (BBL), injection, in one of the two nasolabial fold (NLF) and Control Product belotero balance (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 milliliter (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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Jan 25, 2018	Sep 11, 2019

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

The safety evaluation set (SES) included all participants who were enrolled into the study, randomized, and received an injection.

Arm/Group Information

ID	Title	Description
BG000	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.

Units	Counts
Participants	BG00052

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00058.4± 10.2

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00047
Male	BG0005

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Hispanic or Latino

Title	Measurements
	BG0001

Not Hispanic and not Latino

Title	Measurements
	BG000

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Black or African American

Title	Measurements
	BG00016

Caucasian

Title	Measurements
	BG000

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00052

Fitzpatrick Skin Type

Skin type I = white; very fair, red or blonde hair blue eyes; freckles; always burns, never tans, skin type II = white, fair, red or blond hair; blue, hazel or green eyes; usually burns, tans with difficulty, skin type III = cream white; fair with any eye or hair color (common); sometimes mild burn, gradually tans, skin type IV = brown; typical Mediterranean Caucasian skin; rarely burns, tans with ease, skin type V = dark brown; mid-eastern skin types; very rarely burns, tans easily, and skin type VI = black; never burns, tans very easily.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Skin Type I	BG0001
Skin Type II	BG000

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

The full analysis set (FAS) included all randomized participants and were analyzed as randomized.

Posted

Mean

Standard Deviation

score on a scale

Day 1

ID	Title	Description
OG000	Test Product: BBL	Participants received treatment with Test Product BBL, injection, in one of the two NLF on Day 1. The BBL 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 injection on Week 2.
OG001	Control Product: BB	Participants received treatment with Control Product BB without lidocaine, injection, in the contralateral NLF on Day 1. The 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 BB injection on Week 2.

Units	Counts
Participants	OG00052 OG00152

Title

Denominators

Categories

Title	Measurements
	OG0003.07± 1.88 OG0015.94± 2.41

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		t-test, 2 sided		<0.0001	p-value from paired two-sided t-tests of no difference between test and control groups.	Mean Difference (Net)	-2.88			2-Sided	95	-3.42	-2.33					Superiority

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.

The FAS included all randomized participants and was analyzed as randomized. Participants who were evaluable for this measure at given time period were included.

Posted

Number

percentage of participants

Week 6

ID	Title	Description
OG000	Test Product: BBL	Participants received treatment with Test Product BBL, injection, in one of the two NLF on Day 1. The BBL 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 injection on Week 2.
OG001	Control Product: BB	Participants received treatment with Control Product BB without lidocaine, injection, in the contralateral NLF on Day 1. The 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 BB injection on Week 2.

Secondary

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

The SES included all participants who were enrolled into the study, randomized, and received an injection.

Posted

Number

participants

Baseline up to Week 6

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

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.

The SES included all participants who were enrolled into the study, randomized, and received an injection.

Posted

Number

participants

Baseline up to Week 6

ID	Title	Description
OG000	Test Product: BBL	Participants received treatment with Test Product BBL, injection, in one of the two NLF on Day 1. The BBL 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 injection on Week 2.
OG001	Control Product: BB	Participants received treatment with Control Product BB without lidocaine, injection, in the contralateral NLF on Day 1. The 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 BB injection on Week 2.

Secondary

Number of Participants With Incidence of Any CTR by Severity Evaluated Using Participant Diaries

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.

Posted

Number

participants

Baseline up to Week 6

ID	Title	Description
OG000	Test Product: BBL	Participants received treatment with Test Product BBL, injection, in one of the two NLF on Day 1. The BBL 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 injection on Week 2.
OG001	Control Product: BB	Participants received treatment with Control Product BB without lidocaine, injection, in the contralateral NLF on Day 1. The 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 BB injection on Week 2.

Secondary

Number of Participants With Incidence of Any CTR by Duration Evaluated Using Participant Diaries

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.

Posted

Number

participants

Baseline up to Week 6

ID	Title	Description
OG000	Test Product: BBL	Participants received treatment with Test Product BBL, injection, in one of the two NLF on Day 1. The BBL 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 injection on Week 2.
OG001	Control Product: BB	Participants received treatment with Control Product BB without lidocaine, injection, in the contralateral NLF on Day 1. The 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 BB injection on Week 2.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	0	52	0	52	5	52

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Headache	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0002 affected52 at risk
Gastroenteritis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 affected52 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0001 affected52 at risk
Skin tightness	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected52 at risk