Trial Outcomes & Findings for Evaluation of Effectiveness and Safety of Belotero Balance® (+) Lidocaine for Volume Augmentation of the Infraorbital Hollow (NCT NCT04594239)

Last Updated: 2024-01-30

Results Overview

Responder rate was defined as percentage of subjects with treatment response at Week 8 on MIHAS, as assessed live by a blinded evaluator. Responders were defined as subjects who achieved greater than or equal to (\>=) 1 grade improvement on both IOHs on the MIHAS. MIHAS (to assess infraorbital hollow) was a 5-point scale ranging as: Grade 0 (none to minimal), Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (extreme). A higher score indicated extreme signs of hollowing. This analysis was done using multiple imputation method to impute missing MIHAS scores. Percentage of subjects with response at Week 8 and corresponding confidence intervals were average values obtained from the multiple imputation approach.

Recruitment status

COMPLETED

Study phase

Target enrollment

150 participants

Primary outcome timeframe

Week 8

Results posted on

2024-01-30

Participant Flow

Subjects were recruited from 9 investigational sites in the United States.

Of the 187 screened subjects, 37 were exited as screen failures.150 subjects were enrolled and randomized in this study.

Participant milestones

Participant milestones
Measure	Belotero Balance (+) Lidocaine (BBL) Treatment With Needle Subjects received a single treatment of BBL injection using needle in both infraorbital hollow (IOH) areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	BBL Treatment With Cannula Subjects received a single treatment of BBL injection using cannula in both IOH areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	Control/Delayed-treatment BBL With Needle Subjects were untreated until Week 8 and then received a single treatment of BBL injection using needle in both IOH areas. Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	Control/Delayed-treatment BBL With Cannula Subjects were untreated until Week 8 and then received a single treatment of BBL injection using cannula in both IOH areas. Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.
Overall Study STARTED	49	48	27	26
Overall Study Safety Population	49	48	26	21
Overall Study COMPLETED	38	39	21	15
Overall Study NOT COMPLETED	11	9	6	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Belotero Balance (+) Lidocaine (BBL) Treatment With Needle Subjects received a single treatment of BBL injection using needle in both infraorbital hollow (IOH) areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	BBL Treatment With Cannula Subjects received a single treatment of BBL injection using cannula in both IOH areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	Control/Delayed-treatment BBL With Needle Subjects were untreated until Week 8 and then received a single treatment of BBL injection using needle in both IOH areas. Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	Control/Delayed-treatment BBL With Cannula Subjects were untreated until Week 8 and then received a single treatment of BBL injection using cannula in both IOH areas. Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.
Overall Study Withdrawal by Subject	3	4	2	4
Overall Study Lost to Follow-up	8	5	4	6
Overall Study Subject relocated	0	0	0	1

Baseline Characteristics

Evaluation of Effectiveness and Safety of Belotero Balance® (+) Lidocaine for Volume Augmentation of the Infraorbital Hollow

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BBL Treatment With Needle n=49 Participants Subjects received a single treatment of BBL injection using needle in both IOH areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	BBL Treatment With Cannula n=48 Participants Subjects received a single treatment of BBL injection using cannula in both IOH areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	Control/Delayed-treatment BBL With Needle n=27 Participants Subjects were untreated until Week 8 and then received a single treatment of BBL injection using needle in both IOH areas. Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	Control/Delayed-treatment BBL With Cannula n=26 Participants Subjects were untreated until Week 8 and then received a single treatment of BBL injection using cannula in both IOH areas. Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	Total n=150 Participants Total of all reporting groups
Age, Continuous	44.0 years STANDARD_DEVIATION 9.06 • n=5 Participants	44.3 years STANDARD_DEVIATION 9.05 • n=7 Participants	43.2 years STANDARD_DEVIATION 10.83 • n=5 Participants	40.0 years STANDARD_DEVIATION 9.18 • n=4 Participants	43.3 years STANDARD_DEVIATION 9.45 • n=21 Participants
Sex: Female, Male Female	44 Participants n=5 Participants	36 Participants n=7 Participants	22 Participants n=5 Participants	23 Participants n=4 Participants	125 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	12 Participants n=7 Participants	5 Participants n=5 Participants	3 Participants n=4 Participants	25 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	20 Participants n=5 Participants	16 Participants n=7 Participants	7 Participants n=5 Participants	7 Participants n=4 Participants	50 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants	32 Participants n=7 Participants	20 Participants n=5 Participants	19 Participants n=4 Participants	100 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants	17 Participants n=21 Participants
Race (NIH/OMB) White	40 Participants n=5 Participants	33 Participants n=7 Participants	19 Participants n=5 Participants	17 Participants n=4 Participants	109 Participants n=21 Participants
Race (NIH/OMB) More than one race	5 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants	16 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Week 8

Population: ITT. As planned, the data for this outcome measure was analyzed for pooled BBL treatment groups (needle and cannula), BBL treatment with needle group, BBL treatment with cannula group and pooled control/delayed-treatment groups BBL (needle and cannula).

Outcome measures

Outcome measures
Measure	BBL Treatment: All Subjects n=97 Participants Subjects received a single treatment of BBL injection using needle and cannula in IOH area at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	BBL Treatment With Needle n=49 Participants Subjects received a single treatment of BBL injection using needle in both IOH areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	BBL Treatment With Cannula n=48 Participants Subjects received a single treatment of BBL injection using cannula in both IOH areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	Control/Delayed-treatment BBL: All Subjects n=53 Participants Subjects were untreated until Week 8 and then received a single treatment of BBL injection using needle and cannula in both IOH areas. Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.
Responder Rate Based on Merz Infraorbital Hollow Assessment Scale (MIHAS) at Week 8	80.6 percentage of subjects Interval 71.4 to 87.4	87.4 percentage of subjects Interval 75.0 to 94.1	73.7 percentage of subjects Interval 59.4 to 84.3	1.9 percentage of subjects Interval 0.3 to 10.2

SECONDARY outcome

Timeframe: Week 8

Population: ITT. Here "overall number of subjects analyzed" were subjects who were evaluable for this outcome measure that is, subjects with observed data. As planned, the data for this outcome measure was calculated and analyzed only for subjects randomized to the treatment groups (needle and cannula).

The GAIS is a 7-point scale ranging as +3 (very much improved); +2 (much improved); +1 (improved); 0 (no change); -1 (worse); -2 (much worse); -3 (very much worse), as assessed by the investigator. An improvement on the GAIS was classified as "improved", "much improved", or "very much improved.

Outcome measures

Outcome measures
Measure	BBL Treatment: All Subjects n=46 Participants Subjects received a single treatment of BBL injection using needle and cannula in IOH area at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	BBL Treatment With Needle n=43 Participants Subjects received a single treatment of BBL injection using needle in both IOH areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	BBL Treatment With Cannula Subjects received a single treatment of BBL injection using cannula in both IOH areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	Control/Delayed-treatment BBL: All Subjects Subjects were untreated until Week 8 and then received a single treatment of BBL injection using needle and cannula in both IOH areas. Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.
Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator Very Much Improved (+3)	47.8 percentage of subjects	44.2 percentage of subjects	—	—
Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator Much Improved (+2)	41.3 percentage of subjects	25.6 percentage of subjects	—	—
Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator Improved (+1)	8.7 percentage of subjects	30.2 percentage of subjects	—	—
Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator No Change (0)	2.2 percentage of subjects	0 percentage of subjects	—	—
Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator Worse (-1)	0 percentage of subjects	0 percentage of subjects	—	—
Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator Much Worse (-2)	0 percentage of subjects	0 percentage of subjects	—	—
Percentage of Subjects With Global Aesthetic Improvement Scale (GAIS) Score at Week 8, as Assessed by the Treating Investigator Very Much Worse (-3)	0 percentage of subjects	0 percentage of subjects	—	—

SECONDARY outcome

Timeframe: Week 8

The GAIS is a 7-point scale ranging as +3 (very much improved); +2 (much improved); +1 (improved); 0 (no change); -1 (worse); -2 (much worse); -3 (very much worse), as assessed by the subject. An improvement on the GAIS was classified as "improved", "much improved", or "very much improved.

Outcome measures

Outcome measures
Measure	BBL Treatment: All Subjects n=46 Participants Subjects received a single treatment of BBL injection using needle and cannula in IOH area at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	BBL Treatment With Needle n=43 Participants Subjects received a single treatment of BBL injection using needle in both IOH areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	BBL Treatment With Cannula Subjects received a single treatment of BBL injection using cannula in both IOH areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	Control/Delayed-treatment BBL: All Subjects Subjects were untreated until Week 8 and then received a single treatment of BBL injection using needle and cannula in both IOH areas. Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.
Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject Very Much Improved (+3)	34.8 percentage of subjects	30.2 percentage of subjects	—	—
Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject Much Improved (+2)	45.7 percentage of subjects	37.2 percentage of subjects	—	—
Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject Improved (+1)	19.6 percentage of subjects	32.6 percentage of subjects	—	—
Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject No Change (0)	0 percentage of subjects	0 percentage of subjects	—	—
Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject Worse (-1)	0 percentage of subjects	0 percentage of subjects	—	—
Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject Much Worse (-2)	0 percentage of subjects	0 percentage of subjects	—	—
Percentage of Subjects With GAIS Score at Week 8, as Assessed by the Subject Very Much Worse (-3)	0 percentage of subjects	0 percentage of subjects	—	—

SECONDARY outcome

Timeframe: Baseline, Week 8

The FACE-Q is a set of standardized patient-reported outcome scales for subjects undergoing facial cosmetic procedures. Subjects answered 7 questions of the FACE-Q satisfaction with eyes using a 4- point scale where: 1(very dissatisfied), 2 (somewhat dissatisfied), 3 (somewhat satisfied), 4 (very satisfied). The sum FACE-Q scores were Rasch-transformed and ranged from 0 to 100. Higher scores reflected a better outcome (greater satisfaction).

Outcome measures

Outcome measures
Measure	BBL Treatment: All Subjects n=46 Participants Subjects received a single treatment of BBL injection using needle and cannula in IOH area at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	BBL Treatment With Needle n=43 Participants Subjects received a single treatment of BBL injection using needle in both IOH areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	BBL Treatment With Cannula Subjects received a single treatment of BBL injection using cannula in both IOH areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	Control/Delayed-treatment BBL: All Subjects Subjects were untreated until Week 8 and then received a single treatment of BBL injection using needle and cannula in both IOH areas. Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.
Change From Baseline in Rasch-Transformed Score for the Face-Q Satisfaction With Eyes at Week 8	27.4 score on a scale Standard Deviation 26.0	24.6 score on a scale Standard Deviation 27.9	—	—

SECONDARY outcome

Timeframe: BBL Treatment (Needle and Cannula): Up to 80 weeks; Control/Delayed-treatment BBL (Needle and Cannula): Up to 56 weeks

Population: The Safety Population (SP) included all treated subjects.

TEAEs are defined as adverse events (AEs) with onset or worsening on or after date and time of first dose of study treatment. A TEAE was considered to be "related" if a causal relationship between BBL and the TEAE is at least reasonably possible.

Outcome measures

Outcome measures
Measure	BBL Treatment: All Subjects n=49 Participants Subjects received a single treatment of BBL injection using needle and cannula in IOH area at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	BBL Treatment With Needle n=48 Participants Subjects received a single treatment of BBL injection using needle in both IOH areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	BBL Treatment With Cannula n=26 Participants Subjects received a single treatment of BBL injection using cannula in both IOH areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	Control/Delayed-treatment BBL: All Subjects n=21 Participants Subjects were untreated until Week 8 and then received a single treatment of BBL injection using needle and cannula in both IOH areas. Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Related to BBL	5 Participants	6 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: BBL Treatment (Needle and Cannula): Up to 80 weeks; Control/Delayed-treatment BBL (Needle and Cannula): Up to 56 weeks

Population: SP.

TESAEs included TEAEs that resulted in death, required either inpatient hospitalization or the prolongation of hospitalization, were life-threatening, resulted in a persistent or significant disability/incapacity or resulted in a congenital anomaly/birth defect. A TESAE was considered to be "related" if a causal relationship between BBL and the TESAE is at least reasonably possible.

Outcome measures

Outcome measures
Measure	BBL Treatment: All Subjects n=49 Participants Subjects received a single treatment of BBL injection using needle and cannula in IOH area at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	BBL Treatment With Needle n=48 Participants Subjects received a single treatment of BBL injection using needle in both IOH areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	BBL Treatment With Cannula n=26 Participants Subjects received a single treatment of BBL injection using cannula in both IOH areas at Day 1 and 48 weeks after last injection (optional retreatment). Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.	Control/Delayed-treatment BBL: All Subjects n=21 Participants Subjects were untreated until Week 8 and then received a single treatment of BBL injection using needle and cannula in both IOH areas. Subjects were eligible to receive an optional touch-up injection 4 weeks after initial injection.
Number of Subjects With Treatment-Emergent Serious Adverse Events (TESAEs) Related to BBL	0 Participants	0 Participants	0 Participants	0 Participants

Adverse Events

BBL Treatment With Needle

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths