A Study of Treatment Preference During Cheek Contouring Comparing Restylane® SubQ With and Without the Addition of Lidocaine Hydrochloride

• Sponsor: Galderma R&D (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01431755
• Collaborator: (none)
• Enrollment: 54
• Locations: 3
• Arms: 2
• Duration (Months): 13
• Patients Per Site: 18
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The objectives of this study are to evaluate the pain-relieving effect and safety of adding lidocaine hydrochloride to Restylane SubQ and to evaluate the esthetic improvement obtained. The study products will be administered in the cheek.

Condition or Disease	Intervention/Treatment	Phase
Facial Tissue Augmentation	Device: Restylane SubQ; Device: Restylane SubQ Lidocaine	N/A

Detailed Description

The Restylane SubQ gel is intended to be used for facial tissue augmentation. The lidocaine content is designed to reduce the subject's pain during treatment. The objectives of this split-face designed study are to evaluate the pain-relieving effect and safety of adding lidocaine hydrochloride to Restylane SubQ and to evaluate the esthetic improvement obtained with the dermal filler using the global esthetic improvement scale (GEIS).

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Official Title: A Randomised, Subject-blinded Study of Treatment Preference During Cheek Contouring Comparing Restylane® SubQ With and Without the Addition of Lidocaine Hydrochloride 0.3%
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Other: Restylane SubQ	Device: Restylane SubQ; Treatment with up to 2 ml of the product
Other: Restylane SubQ Lidocaine	Device: Restylane SubQ Lidocaine; Treatment with up to 2 ml of the product

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects Who Assessed Treatment With Restylane SubQ Lidocaine as Least Painful. [When injection of both cheeks were completed]

   When injection of both cheeks was completed, the subject was asked which treatment was least painful (right cheek/left cheek/both cheeks alike).

Secondary Outcome Measures

1. Subject Pain Assessment by Visual Analogue Scale (VAS) 15 and 120 Minutes After Treatment. [15 and 120 minutes]

   Pain was assessed during the first 2 hours after the initial injection of the study products using a 100 mm VAS. The endpoints of the scale were "no pain" (0 mm) and "worst possible pain" (100 mm). Pain was assessed at the time points 15, 30, 60, 90 and 120 minutes after injection.

2. Percentage of Improved Subjects at 2 Weeks After Treatment as Assessed by Use of Global Esthetic Improvement Scale (GEIS) [2 weeks]

   Esthetic improvement was evaluated by using Global Esthetic Improvement Scale. GEIS was evaluated by comparing current photos with pre-treatment photos and using a 5-graded scale (worse/no change/somewhat improved/much improved/very much improved). A clinically significant global esthetic improvement was defined as a score of somewhat improved, much improved or very much improved. GEIS was assessed by the Investigator and the subject. Each cheek/study product was evaluated separately. GEIS was assessed at the time points 2 weeks, 3 months, 2 weeks after re-treatment and 6, 9 and 12 months after first treatment.

3. Percentage of Subjects With at Least One Step Improvement on Medicis Midface Volume Scale (MMVS) at 2 Weeks [2 weeks]

   The severity of midface volume loss or midface contour deficiency was assessed by the investigators using a 4-graded scale, Medicis Midface Volume Scale -MMVS (1, fairly full; 2, mild loss of fullness; 3, moderate loss, slight hollowing; and 4, substantial loss, clearly apparent hollowing). Each score were exemplified by photographic images on the scale. A one grade decrease in score from screening was defined as a treatment success/improvement.The efficacy in terms of Medicis Midface Volume Scale (MMVS) was assessed by the Investigator per treatment group. The two cheeks were evaluated separately. MMVS was assessed at the time points 2 weeks, 3 months, 2 weeks after re-treatment and 6, 9 and 12 months after first treatment.

4. Number of Subjects Reporting at Least 1 Diary Complaint Related to the Cheek Treated With Restylane SubQ and Restylane SubQ Lidocaine Respectively After Initial Treatment. [14 days]

   A subject diary was completed for 14 days following the initial treatment and the optional re-treatment at the 3-month visit. Each subject was asked to record the presence of bruising, redness, swelling, pain, tenderness and itching.

5. Number of Subjects Reporting Adverse Event [Up to 12 months]

   Adverse Events (AEs) were collected by open questioning, information obtained from signs and symptoms detected during examination, observed by the study personnel or spontaneous reports from the subjects. All subjects were injected with Restylane SubQ in one cheek and Restylane SubQ Lidocaine in the contralateral cheek.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• 18 years of age or older.

• Intent to undergo contouring of both cheeks with 1.5 to 2 ml Restylane SubQ per cheek.

• Sufficient symmetry of the face in order to ensure similar volume to be injected, similar injection technique and time for injection.

• Signed informed consent.

Exclusion Criteria:

• Surgery in the midface including aesthetic facial surgical therapy, sinus surgery or dental root surgery within the past 12 months.

• Chronic infection in head and neck region.

• Ongoing infections in mouth.

• Tendency for edema, puffiness or swelling over the zygomatic prominence.

• Active skin disease, inflammation or related conditions, such as infection, psoriasis and herpes zoster near or on the area to be treated.

• Previous hypersensitivity to hyaluronic acid or local anesthetics.

• Concomitant anticoagulant therapy and therapy with inhibitors of platelet aggregation within 10 days prior to treatment, or a history of bleeding disorders.

• Cancerous or pre-cancerous lesions in the area to be treated.

• Previous tissue augmenting therapy in the area to be treated with non-permanent filler, laser treatment, or chemical peeling during the last 6 months.

• Permanent implant placed in the area to be treated.

• Reduced sensibility in the facial region e.g. due to trauma, facial pareses, previous tissue augmenting therapy, aesthetic facial surgical therapy, laser treatment, or peeling.

• Pregnancy or breast feeding.

• Participation in any other clinical study within 30 days prior to inclusion.

• Other condition preventing the subject to entering the study in the Investigator's opinion e.g. subjects not likely to avoid other facial cosmetic treatments below the level of the upper orbital rim, subjects anticipated to be unreliable or incapable of understanding the VAS assessment, insufficient tissue support or cover of the treatment area.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Plastikkirurggruppen	Stockholm		Sweden	113 24
2	ZMedical	Stockholm		Sweden	114 36
3	Akademikliniken	Stockholm		Sweden	115 42

Sponsors and Collaborators

• Galderma R&D

Investigators

• Principal Investigator: Per Hedén, M.D., Akademikliniken, Storängsvägen 10, 115 42 Stockholm

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Galderma R&D
• ClinicalTrials.gov Identifier: NCT01431755
• Other Study ID Numbers: 31GE1101
• First Posted: Sep 12, 2011
• Last Update Posted: May 9, 2014
• Last Verified: Apr 1, 2014

• Additional relevant MeSH terms: Lidocaine; Hyaluronic Acid

Study Results

Participant Flow

Recruitment Details	First subject enrolled: September 10, 2011 Last subject visit: October 19, 2012
Pre-assignment Detail	The study has split-face design. Each subject is randomized to treatment with Restylane SubQ in one cheek and Restylane SubQ Lidocaine in the contralateral cheek.

Arm/Group Title	Restylane SubQ/Restylane SubQ Lidocaine
Arm/Group Description	The study has a split-face design. Each subject was injected with Restylane SubQ in one cheek and Restylane SubQ Lidocaine in the contralateral cheek as randomized. Half of the subjects received both study products by injections with a sharp needle and the other half received both study products by injection with a blunt ended microcannula. Following the initial treatment there was a one year follow-up period including an optional re-treatment at 3 months. A maximum volume of 2 ml per cheek and session was recommended.
Period Title: Overall Study
STARTED	54
COMPLETED	49
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Restylane SubQ/Restylane SubQ Lidocaine
Arm/Group Description	The study has a split-face design. Each subject was injected with Restylane SubQ in one cheek and Restylane SubQ Lidocaine in the contralateral cheek as randomized. Half of the subjects received both study products by injections with a sharp needle and the other half received both study products by injection with a blunt ended microcannula. Following the initial treatment there was a one year follow-up period including an optional re-treatment at 3 months. A maximum volume of 2 ml per cheek and session was recommended
Overall Participants	54
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	45 83.3%
>=65 years	9 16.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53 (13.1)
Sex: Female, Male (Count of Participants)
Female	51 94.4%
Male	3 5.6%
Region of Enrollment (participants) [Number]
Sweden	54 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects Who Assessed Treatment With Restylane SubQ Lidocaine as Least Painful.
Description	When injection of both cheeks was completed, the subject was asked which treatment was least painful (right cheek/left cheek/both cheeks alike).
Time Frame	When injection of both cheeks were completed

Outcome Measure Data

Analysis Population Description

Intention to treat. 54/54 subjects

Arm/Group Title	Restylane SubQ/Restylane SubQ Lidocaine
Arm/Group Description	The study has a split-face design. Each subject was injected with Restylane SubQ in one cheek and Restylane SubQ Lidocaine in the contralateral cheek as randomized. Half of the subjects received both study products by injections with a sharp needle and the other half received both study products by injection with a blunt ended microcannula. Following the initial treatment there was a one year follow-up period including an optional re-treatment at 3 months. A maximum volume of 2 ml per cheek and session was recommended.
Measure Participants	54
Number (95% Confidence Interval) [percentage of participants]	100 185.2%

2. Secondary Outcome

Title	Subject Pain Assessment by Visual Analogue Scale (VAS) 15 and 120 Minutes After Treatment.
Description	Pain was assessed during the first 2 hours after the initial injection of the study products using a 100 mm VAS. The endpoints of the scale were "no pain" (0 mm) and "worst possible pain" (100 mm). Pain was assessed at the time points 15, 30, 60, 90 and 120 minutes after injection.
Time Frame	15 and 120 minutes

Outcome Measure Data

Analysis Population Description

Intention to treat. 54/54 subjects

Arm/Group Title	Restylane SubQ/Restylane SubQ Lidocaine
Arm/Group Description	The study has a split-face design. Each subject was injected with Restylane SubQ in one cheek and Restylane SubQ Lidocaine in the contralateral cheek as randomized. Half of the subjects received both study products by injections with a sharp needle and the other half received both study products by injection with a blunt ended microcannula. Following the initial treatment there was a one year follow-up period including an optional re-treatment at 3 months. A maximum volume of 2 ml per cheek and session was recommended.
Measure Participants	54
Restylane SubQ, VAS at 15 minutes	28.4 (20.6)
Restylane SubQ Lidocaine, VAS at 15 minutes	2.9 (4.1)
Restylane SubQ, VAS at 120 minutes	7.3 (11.1)
Restylane SubQ Lidocaine, VAS at 120 minutes	1.3 (3.3)

3. Secondary Outcome

Title	Percentage of Improved Subjects at 2 Weeks After Treatment as Assessed by Use of Global Esthetic Improvement Scale (GEIS)
Description	Esthetic improvement was evaluated by using Global Esthetic Improvement Scale. GEIS was evaluated by comparing current photos with pre-treatment photos and using a 5-graded scale (worse/no change/somewhat improved/much improved/very much improved). A clinically significant global esthetic improvement was defined as a score of somewhat improved, much improved or very much improved. GEIS was assessed by the Investigator and the subject. Each cheek/study product was evaluated separately. GEIS was assessed at the time points 2 weeks, 3 months, 2 weeks after re-treatment and 6, 9 and 12 months after first treatment.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat. 54/54 subjects

Arm/Group Title	Restylane SubQ/Restylane SubQ Lidocaine
Arm/Group Description	The study has a split-face design. Each subject was injected with Restylane SubQ in one cheek and Restylane SubQ Lidocaine in the contralateral cheek as randomized. Half of the subjects received both study products by injections with a sharp needle and the other half received both study products by injection with a blunt ended microcannula. Following the initial treatment there was a one year follow-up period including an optional re-treatment at 3 months. A maximum volume of 2 ml per cheek and session was recommended.
Measure Participants	54
Restylane SubQ, subject GEIS, improved	90.7 168%
Restylane SubQ, investigator GEIS, improved	96.3 178.3%
Restylane SubQ Lidocain, subject GEIS, improved	92.6 171.5%
Restylane SubQ Lidocaine, invest. GEIS, improved	100.0 185.2%

4. Secondary Outcome

Title	Percentage of Subjects With at Least One Step Improvement on Medicis Midface Volume Scale (MMVS) at 2 Weeks
Description	The severity of midface volume loss or midface contour deficiency was assessed by the investigators using a 4-graded scale, Medicis Midface Volume Scale -MMVS (1, fairly full; 2, mild loss of fullness; 3, moderate loss, slight hollowing; and 4, substantial loss, clearly apparent hollowing). Each score were exemplified by photographic images on the scale. A one grade decrease in score from screening was defined as a treatment success/improvement.The efficacy in terms of Medicis Midface Volume Scale (MMVS) was assessed by the Investigator per treatment group. The two cheeks were evaluated separately. MMVS was assessed at the time points 2 weeks, 3 months, 2 weeks after re-treatment and 6, 9 and 12 months after first treatment.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat. 54/54 subjects

Arm/Group Title	Restylane SubQ/Restylane SubQ Lidocaine
Arm/Group Description	The study has a split-face design. Each subject was injected with Restylane SubQ in one cheek and Restylane SubQ Lidocaine in the contralateral cheek as randomized. Half of the subjects received both study products by injections with a sharp needle and the other half received both study products by injection with a blunt ended microcannula. Following the initial treatment there was a one year follow-up period including an optional re-treatment at 3 months. A maximum volume of 2 ml per cheek and session was recommended.
Measure Participants	54
Restylane SubQ, improved MMVS at 2 weeks	55.6 103%
Restylane SubQ Lidocaine, improved MMVS at 2 weeks	59.3 109.8%

5. Secondary Outcome

Title	Number of Subjects Reporting at Least 1 Diary Complaint Related to the Cheek Treated With Restylane SubQ and Restylane SubQ Lidocaine Respectively After Initial Treatment.
Description	A subject diary was completed for 14 days following the initial treatment and the optional re-treatment at the 3-month visit. Each subject was asked to record the presence of bruising, redness, swelling, pain, tenderness and itching.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

Safety Population. 54/54 subjects.

Arm/Group Title	Restylane SubQ/Restylane SubQ Lidocaine
Arm/Group Description	The study has a split-face design. Each subject was injected with Restylane SubQ in one cheek and Restylane SubQ Lidocaine in the contralateral cheek as randomized. Half of the subjects received both study products by injections with a sharp needle and the other half received both study products by injection with a blunt ended microcannula. Following the initial treatment there was a one year follow-up period including an optional re-treatment at 3 months. A maximum volume of 2 ml per cheek and session was recommended.
Measure Participants	54
Restylane SubQ	54 100%
Restylane SubQ Lidocaine	52 96.3%

6. Secondary Outcome

Title	Number of Subjects Reporting Adverse Event
Description	Adverse Events (AEs) were collected by open questioning, information obtained from signs and symptoms detected during examination, observed by the study personnel or spontaneous reports from the subjects. All subjects were injected with Restylane SubQ in one cheek and Restylane SubQ Lidocaine in the contralateral cheek.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

Safety population, 54 subjects.

Arm/Group Title	Restylane SubQ/Restylane SubQ Lidocaine
Arm/Group Description	The study has a split-face design. Each subject was injected with Restylane SubQ in one cheek and Restylane SubQ Lidocaine in the contralateral cheek as randomized. Half of the subjects received both study products by injections with a sharp needle and the other half received both study products by injection with a blunt ended microcannula. Following the initial treatment there was a one year follow-up period including an optional re-treatment at 3 months. A maximum volume of 2 ml per cheek and session was recommended.
Measure Participants	54
Number [participants]	41 75.9%

Adverse Events

Time Frame	From treatment up to 12 months
Adverse Event Reporting Description	Adverse Events (AEs) were collected by open questioning, information obtained from signs and symptoms detected during examination, observed by the study personnel or spontaneous reports from the subjects.
Arm/Group Title	Restylane SubQ/Restylane SubQ Lidocaine: Systemic		Restylane SubQ: Localized		Restylane SubQ Lidocaine: Localized
Arm/Group Description	The study has a split-face design. Each subject was injected with Restylane SubQ in one cheek and Restylane SubQ Lidocaine in the contralateral cheek as randomized. Half of the subjects received both study products by injections with a sharp needle and the other half received both study products by injection with a blunt ended microcannula. Following the initial treatment there was a one year follow-up period including an optional re-treatment at 3 months. A maximum volume of 2 ml per cheek and session was recommended.Hence, all subjects received injections with both products at the same time.		The study has a split-face design. Each subject was injected with Restylane SubQ in one cheek and Restylane SubQ Lidocaine in the contralateral cheek as randomized. Half of the subjects received both study products by injections with a sharp needle and the other half received both study products by injection with a blunt ended microcannula. Following the initial treatment there was a one year follow-up period including an optional re-treatment at 3 months. A maximum volume of 2 ml per cheek and session was recommended.Hence, all subjects received injections with both products at the same time		The study has a split-face design. Each subject was injected with Restylane SubQ in one cheek and Restylane SubQ Lidocaine in the contralateral cheek as randomized. Half of the subjects received both study products by injections with a sharp needle and the other half received both study products by injection with a blunt ended microcannula. Following the initial treatment there was a one year follow-up period including an optional re-treatment at 3 months. A maximum volume of 2 ml per cheek and session was recommended.Hence, all subjects received injections with both products at the same time
All Cause Mortality
	Restylane SubQ/Restylane SubQ Lidocaine: Systemic		Restylane SubQ: Localized		Restylane SubQ Lidocaine: Localized
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Restylane SubQ/Restylane SubQ Lidocaine: Systemic		Restylane SubQ: Localized		Restylane SubQ Lidocaine: Localized
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/54 (7.4%)		0/54 (0%)		0/54 (0%)
Cardiac disorders
Cardiac Failure	1/54 (1.9%)	1	0/54 (0%)	0	0/54 (0%)	0
Atrial Fibrillation	1/54 (1.9%)	1	0/54 (0%)	0	0/54 (0%)	0
Gastrointestinal disorders
Peptic Ulcer Hemorrhage	1/54 (1.9%)	1	0/54 (0%)	0	0/54 (0%)	0
Vascular disorders
Mesenteric Vein Thrombosis	1/54 (1.9%)	1	0/54 (0%)	0	0/54 (0%)	0
Other (Not Including Serious) Adverse Events
	Restylane SubQ/Restylane SubQ Lidocaine: Systemic		Restylane SubQ: Localized		Restylane SubQ Lidocaine: Localized
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/54 (16.7%)		25/54 (46.3%)		20/54 (37%)
General disorders
Implant site inflammation	0/54 (0%)	0	11/54 (20.4%)	30	10/54 (18.5%)	21
Implant site swelling	0/54 (0%)	0	6/54 (11.1%)	7	5/54 (9.3%)	5
Injection site pain	0/54 (0%)	0	9/54 (16.7%)	9	4/54 (7.4%)	4
Implant site nodule	0/54 (0%)	0	7/54 (13%)	7	4/54 (7.4%)	4
Implant Site Pruritus	0/54 (0%)	0	3/54 (5.6%)	4	4/54 (7.4%)	7
Implant site erythema	0/54 (0%)	0	3/54 (5.6%)	3	3/54 (5.6%)	3
Implant site haematoma	0/54 (0%)	0	5/54 (9.3%)	5	0/54 (0%)	0
Infections and infestations
Nasopharyngitis	6/54 (11.1%)	6	0/54 (0%)	0	0/54 (0%)	0
Nervous system disorders
Headache	4/54 (7.4%)	4	0/54 (0%)	0	0/54 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Any publication or presentation by PI shall be submitted to Q-Med for review no less than 60 days before submission for publication or presentation. Q-Med will provide any comments to Principal Investigator within thirty (30) days following receipt of the proposed publication/presentation. PI agrees to consider, discuss and give reasonable considerations to comments by Q-Med. Q-Med may also request that the Company name or Q-Med employee name appear or not appear in such publication.