In January 2005, the oversight responsibility of the Post-Approval Studies Program was transferred to the Division of Epidemiology (DEPI) of the Office of Surveillance and Biometrics (OSB)/Center for Devices and Radiological Health (CDRH).
The CDRH Post-Approval Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated as a condition of approval of a premarket approval (PMA) application, protocol development product (PDP) application, or humanitarian device exemption (HDE) application. The program helps ensure that well-designed post-approval studies (PAS) are conducted effectively and efficiently and in the least burdensome manner.
CDRH has established an automated, internal tracking system that efficiently identifies the reporting status of active PAS studies ordered since January 1, 2005 based on study timelines incorporated in study protocols and agreed upon by the CDRH and applicants. This system represents CDRH's effort to ensure that all PAS commitments are fulfilled in a timely manner.
In addition, CDRH launched this publicly available webpage to keep all stakeholders informed of the progress of each PAS. The webpage displays general information regarding each PAS, as well as the overall study status (based on protocol-driven timelines and the adequacy of the data) and the applicant's reporting status for each submission due.
Julie Unger
Project Manager, Post-Approval Studies Program
Food and Drug Administration
10903 New Hampshire Ave
WO66-4206v
Silver Spring, MD
20993-0002
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).
150 subjects were randomized and treated. 148 subjects completed 24 weeks of follow-up and skin
test.
Actual Number of Sites Enrolled
9
Patient Followup Rate
98.70%
Final 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.
Study Strengths and 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.
Recommendations for Labeling 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.
