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U.S. Department of Health and Human Services

Post-Approval Studies (PAS)

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The FDA has the authority to require sponsors to perform a post-approval study (or studies) at the time of approval of a premarket approval (PMA), humanitarian device exemption (HDE), or product development protocol (PDP) application. Post-approval studies can provide patients, health care professionals, the device industry, the FDA and other stakeholders information on the continued safety and effectiveness (or continued probable benefit, in the case of an HDE) approved medical devices. This database allows you to search Post-Approval Study information by applicant or device information.

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Application Number P040024 / PAS001
Current Plan Approved 03/25/2005
Study Name Restylane
General Study Protocol Parameters
Study Design Randomized Clinical Trial
Data Source New Data Collection
Comparison Group Concurrent Control
Analysis Type Analytical
Study Population Adult: >21
Detailed Study Protocol Parameters
Study Design Description The study was a prospective, randomized, comparative, efficacy evaluator-blinded, design. Subjects meeting the enrollment criteria will have bilateral nasolabial folds and, if needed, oral commissures corrected with Restylane /Perlane to optimal correction using each product as intended. - One of the sides of the face will be randomly assigned to be corrected with Restylane and the opposite side will be treated with Perlane at Visit 1 and, potentially at Visit T, 2 weeks after for touch-up. - All patients should receive at least a one-grade improvement in WSRS. - The patients will be aware that they are receiving both treatments, but they will not be informed of which treatment is applied to which side of their face (see also paragraph 4.2 regarding Randomization and Blinding Procedure).
Study Population Description This device is indicated for mid-to-deep dermal implantation for the correction of moderate to severe facial wrinkles and folds, such as nasolabial folds. The study population includes patients with Fitzpatrick Skin Types 5 or 6
Sample Size 150 patients from 10 or more centers
Data Collection Assessments include pain, tenderness, redness, ecchymosis, swelling. itching, mass (nodule / cyst / abscess) formation, dermeal pignentation and keloid changes at the site of injection at each follow-up point post-optimal cosinesis. Safety endpoint assessments include: keloid formation at the site of injection at 12 and 24 weeks, 2) pigmentation changes at the site of
injection compared to adjacent skin at 2 and 6 weeks, and 3) adverse experience assessment, 4) patient diary symptom profile. and 5) immunologic panel oUtcomc (to include at a mininmuim histamine release, W1BC diflberential, and anti-body titer).
Follow-up Visits and Length of Follow-up Screen/Baseline, 72 hours, 2 weeks, 6 weeks, 12 weeks and 24 weeks
Final Study Results
Interim Safety Information Study is completed. See Final Study Results
Number of Patients 150 subjects were randomized and treated. 148 subjects completed 24 weeks of follow-up and skin test.
Number of Sites 9
Follow-up Rate 98.70%
Safety Findings Based on skin testing, antibody data and histopathology, neither Restylane nor Perlane are immunogenic. There were no deaths. Three intercurrent serious injuries were unrelated to test products. There were 45 true systemic events that were unrelated to test products or of unknown relationship. There were 36 true local unrelated/unknown events. There were 104 related local adverse experiences all of which were assigned to a specific treatment site. All local related events were expected in incidence, severity and duration. Local adverse experiences were largely limited to bruising, tenderness, edema, redness, itching, pain, and pigmentary changes. These listed events account for over 90% of local related events. No patient developed a keloid during the study. There was one hypertrophic scar reported that was most likely related to inflammatory acne at entry but that resolved spontaneously. There were 9 Perlane-treated patients and 14 Restylane-treated patients with pigmentation changes at the nasolabial fold or oral commissures. All were of mild or moderate severity. Most resolved within 6 weeks with 7/9 Perlane events resolving by 12 weeks. Unintended feel occurred in 3 patients. In one, there was spontaneous resolution. In thetwo others, a nodule developed into an abscess and treatment of the infectious process was successful. There were no delayed onset local related experiences that suggest, therefore, an absence of immune reactivity. There were 17 injection site experiences of pigmentation changes and 14 local related adverse experiences that lasted more than 2 weeks. Adverse experience assessment and analysis demonstrated that there was no difference
between incidence or severity between Restylane and Perlane. The protocol-specified screening analysis of relationship of injection technique to adverse experience failed to identify a significant relationship except generation of a hypothesis that multiple puncture technique may increase pigmentary changes. Patient diary complaints demonstrated a 75% to 90% incidence of local events in the first two weeks of such complaints as bruising, redness, swelling, tenderness, and pain. Itching was less common. Most complaints were mild and predominantly in the initial days followed by resolution by end of the diary period.
Strengths & Weaknesses One of the study strengths is the randomized study design, which allows for control of potential confounders. Another strength is the high follow-up rate.
Label Changes Amend the label with a summary of the postapproval study and findings regarding assessing the likelihood of hypersensitivity reactions, the likelihood of keloid formation, changes in pigmentation and the development of clinically relevant antibodies to Restylane.

Restylane Schedule

Report Schedule
Date Due
FDA Receipt
Applicant's Reporting Status
6 month report 09/23/2005 10/11/2005 Overdue/Received
1 year report 04/25/2006 03/15/2006 On Time
FINAL REPORT 08/15/2006 08/07/2006 On Time

Contact Us

Julie Unger
Project Manager, Post-Approval Studies Program
Food and Drug Administration
10903 New Hampshire Ave
WO66-4206v Silver Spring, MD

Phone: (301) 796-6134
Fax: (301) 847-8140

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