CTA Commercial U.S. Package Insert
`Revision Date: 10/12/06
`
`CONFIDENTIAL
`
`CTA
`Injectable HA Gel
`
`CAUTION: Federal (U.S.) Law restricts this device to sale by or on the order of a physician or
`properly licensed practitioner.
`
`DESCRIPTION
`CTA is a sterile, nonpyrogenic gel implant, composed of hyaluronan produced by Streptococcus
`equi (bacterial fermentation) that is crosslinked and suspended in a buffer solution at a
`concentration of 28 mg/mL. CTA contains 0.3% lidocaine HCI.
`
`INDICATION
`CTA is indicated for injection into the mid to deep dermis for the correction of moderate to
`severe facial wrinkles and folds (such as nasolabial folds).
`
`CONTRAINDICATIONS
`* CTA is contraindicated for patients with severe allergies manifested by a history of
`anaphylaxis or history or presence of multiple severe allergies.
`* CTA is composed of hyaluronic acid, lidocaine and may contain trace amounts of gram
`positive bacterial proteins. CTA is contraindicated for patients with a history of allergies
`to such material.
`
`WARNINGS
`* CTA must not be implanted into blood vessels. Implantation of CTA into dermal vessels
`may cause vascular occlusion, infarction or embolic phenomena.
`* Use of CTA at specific sites in which an active inflammatory process (skin eruptions
`such as cysts, pimples, rashes or hives) or infection is present should be deferred until the
`inflammatory process has been controlled.
`Injection site reactions to CTA have been observed consisting mainly of short-term
`inflammatory symptoms starting early after treatment and lasting <_ 7 days duration.
`Refer to the adverse events section for details.
`
`-
`
`PRECAUTIONS
`General
`* STERILE CONTENTS. The pre-filled syringe is intended for single use only. The
`contents of the syringe should be used immediately after opening. Discard any unused
`CTA. Do not resterilize.
`* Do not use CTA if the package has been opened or damaged or beyond the expiration
`date cited on the package.
`* Based on preclinical studies, patients should be limited to 30 mL of CTA per 60 kg (130
`lbs) body mass per year. The safety of injecting greater amounts has not been
`established.
`* The safety and effectiveness of CTA for the treatment of dermal contour defects other
`than nasolabial folds (e.g., lips) has not been established.
`* The long-term safety and effectiveness of CTA beyond one year have not been
`investigated.
`* As with all transcutaneous procedures, CTA implantation carries a risk of infection,
`Standard precautions associated with injectable materials should be followed.
`* The safety of CTA for use during pregnancy, in breastfeeding females and in patients
`under 1 8 years has not been established.
`
`Page 1 of 8
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`2la
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`Exhibit 1031
`Prollenium v. Allergan
`
`

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`CTA Commercial U.S. Package Insert
`Revision Date: 10/12/06
`
`CONFIDENTIAL
`
`* The safety of CTA in patients with increased susceptibility to keloid formation and
`hypertrophic scarring has not been studied.
`* CTA should be used with caution in patients on immunosuppressive therapy.
`• After use, treatment syringes and needles may be potential biohazards. Handle
`accordingly and dispose of in accordance with accepted medical practice and applicable
`local, state and federal regulations.
`* CTA is a translucent gel without visible particulates. In the event that the contents of the
`syringe show signs of separation, do not use the syringe and notify Anika Therapeutics at
`800-XXX-XXXX.
`* Patients who are using substances that reduce coagulation, such as aspirin and non-
`steroidal anti-inflammatory drugs, may, as with any injection, experience increased
`bruising or bleeding at injection sites.
`* The patient should be informed that he or she should minimize exposure of the treated
`area to excessive sun, UV lamp exposure and extreme cold weather until any initial
`swelling and redness has resolved and puncture sites have healed.
`If laser treatment, chemical peeling or any other procedure based on active dermal
`response is considered after treatment with CTA, there is a possible risk of eliciting an
`inflammatory reaction at the implant site. This also applies if CTA is administered
`before the skin has healed completely after such a procedure.
`
`*
`
`ADVERSE EVENTS
`In a randomized, controlled study to evaluate safety and effectiveness, 208 patients at 10 centers,
`were either injected with CTA in both nasolabial folds (NLF) (n=17) or CTA in one NLF and
`Cosmoplast® in the contralateral NLF (n=19 1). Symptoms reported in patient diaries during 14
`days after treatment are listed in Tables I and 2. Symptom-related Adverse Events recorded by
`investigators at study visits are presented in Table 3.
`
`Page 2 of 8
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`a'I
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`CTA Commercial U.S. Package Insert
`Revision Date: 10/12/06
`
`CONFIDENTIAL
`
`Table 1: Maximum Intensity of Symptoms after Treatment, Patient Diary
`
`Bruising
`
`Redness
`
`Swelling
`
`Pain
`
`CTA
`N=208
`Total
`reporting
`symptoms
`N (%)
`131
`(63.0%)
`151
`(72.6%)
`181
`(87.0%)
`108
`(51.9%)
`145
`(69.7%)
`83
`(39.9%)
`Nodule
`129
`formation
`(62.0%)
`COS=Cosmoplasto
`
`Tenderness
`
`Itching
`
`Side COS Side
`N=191
`Total
`reporting
`symptoms
`N (%)
`94
`(49.2%)
`124
`(64.9%)
`129
`(67.5%)
`63
`(33.0%)
`101
`(52.9%)
`49
`(25.7%)
`112
`(58.6%)
`
`CTA Side
`Int
`Mild
`N (%)
`
`Mode-
`rate
`N (%)
`
`45
`(21.6%)
`45
`(21.6%)
`31
`(14.9%)
`52
`(25.0%)
`57
`(27.4%)
`63
`(30.3%)
`39
`(18.8%)
`
`49
`(23.6%)
`76
`(35.5%)
`78
`(37.5%)
`40
`(19.2%)
`57
`(27.4%)
`10
`(4.8%)
`61
`(29.3%)
`
`Unknown
`N (%)
`
`7
`(3.3%)
`6
`(2.9%)
`11
`(5.3%)
`6
`(2.9%)
`11
`(5.3%)
`7
`(3.4%)
`11
`(5.3%)
`
`Severe
`N (%)
`
`Unknown
`N (%)
`
`30
`(14.4%)
`24
`(11.5%)
`61
`(29.3%)
`14
`(6.7%)
`20
`(9.6%)
`3
`(1.4%)
`18
`(8.7%)
`
`4
`(2.1%)
`6
`(3.1%)
`7
`(3.7%)
`2
`(1.0%)
`6
`(3.1%)
`2
`(1,0%)
`9
`(4.7%)
`
`COS Side
`IntensityIn
`Mild
`Mode-
`N (%)
`rate
`N (%)
`
`58
`(30A4%)
`71
`(37.2%)
`86
`.)
`51
`(26.7%)
`71
`(37.2%)
`43
`(22.5%)
`69
`(36.1%)
`
`26
`(13.6%)
`42
`(22.0%)
`34
`
`9
`(4.7%)
`20
`(10.5%)
`4
`(2.1%)
`32
`(16.8%)
`
`Severe
`N (%)
`
`6
`(3.1%)
`5
`(2.6%)
`2
`(1.0%
`1
`(0.5%)
`4
`(2.1%)
`0
`(0.0%)
`2
`(1.0%)
`
`Table 2: Duration of Symptoms after Treatment, Patient Diary
`
`Bruising
`
`Redness
`
`Swelling
`
`Pain
`
`<=3
`N
`56
`(26.9%)
`79
`(38.0%)
`81
`(38.9%)
`87
`_ (418%)
`83
`(39.9%)
`61
`(29.3%)
`Nodule
`27
`formation
`(13.0%)
`COS=Cosmoplast®
`
`Tenderness
`
`Itching
`
`N
`
`CTA Side (N=208)
`Number of Days
`4-7
`8-13
`N %)
`(% ) N
`51
`17
`(24.5%)
`(8.2%)
`49
`14
`(23.6%)
`(6.7%)
`77
`19
`(37.0%)
`(19.9%)
`15
`3
`(7.2%)
`(1.6%)
`52
`5
`(25.0%)
`(2.4%)
`13
`5
`(6.3%)
`(2.6%)
`28
`48
`(13.5%)
`(23.1%)
`
`14+
`(%)
`7
`(3.7%)
`9
`J47%)
`4
`(2.1%)
`3
`(1.6%)
`5
`(2.6%)
`4
`(2.1%)
`26
`(12.5%)
`
`COS Side (N=191)
`Number of Days
`4-7
`8-13
`(/_(%
`16
`(8.4%)
`13
`
`25
`(13.1%)
`28
`
`28
`(14.7%)
`5
`(2.6%)
`31
`(16.2%)
`7
`(3.7%)
`24
`(12.6%)
`
`11
`(5.8%)
`3
`1.6%)
`7
`(3.7%)
`4
`(2.1° )
`46
`(24.1%)
`
`14+
`N (%)
`6
`(3.1%)
`5
`(2.6%)
`3
`(1.6%)
`3
`1.6%)
`2
`(1.0%)
`3
`1.6%)
`18
`(9.4%)
`
`<=3
`
`N
`
`47
`(24.6%)
`78
`(40.8%)
`87
`(45.5%)
`52
`(27.2%)
`61
`(31 9%
`35
`(18.3/)
`24
`(12.6%)
`
`Table 3: Adverse Events Occurring in >2% of Patients, CTA, Physician Reported
`
`Description of Adverse Event CTA Side Cosmoplast Side
`(WHO Preferred Term)
`(N=208)
`(N=191)
`NN(%)
`N (%)
`59 (27.7%)
`37 (19.4%)
`1(0.5%)
`5 (2.1%)
`3 (1.6%)
`4_(2.1%)
`4(1.0%)
`6_(3.1%)
`5 (2.6%)
`0 (0.0%)
`17 (8.4%)
`15 (7.9%)
`14(6.8%)
`5 (2.6%)
`
`Any Adverse Event
`Injection Site Bruising
`Injection Site Discoloration
`Injection Site Erythema
`Injection Site Edema
`Nodule
`Swelling
`
`Page 3 of 8
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`2=2'-
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`

`CTA Commercial U.S. Package Insert
`Revision Date: 10/12/06
`
`Contusion
`Erythema
`Swelling Face
`
`CONFIDENTIAL
`
`15 (7.3%) I
`2 (1.0%)
`7(3.7%)
`
`4(2.1%)
`4 (2.1%)
`1(0.5%)
`
`Local adverse events
`Local adverse events were observed by the physician in 59/208 subjects treated with CTA in the
`randomized study. Injection site reactions included bruising and edema. Additional non-injection
`site reactions of nodule formation, swelling, contusion and facial swelling account for the majority
`of adverse events observed. In most cases, symptoms (bruising, redness, swelling, pain,
`tenderness, itching, nodule formation) were of mild to moderate intensity and resolved in 7 days
`or less.
`
`Non-local adverse events
`Non-local adverse events occurred in 34/191 (17.8%) of the study subjects. Since each patient
`received both CTA treatment and control, the causality and association of these events could not
`be identified.
`
`Serious Adverse Events
`
`Six subjects experienced serious adverse events. One event (i.e., injection site cellulitis) was
`related to CTA treatment.. The remaining serious adverse events (i.e., difficulty breathing,
`dizziness and chest pain) were not considered related to study treatment.
`
`Extension Study and Retreatment
`185/191 subjects who completed the 6 month evaluation were eligible to continue in an extension
`phase of the study. No adverse events related to treatment were observed at the 9 and 12 month
`follow-up visits for the 101 subjects who were not retreated, but participated in the extension
`phase of the study.
`
`84 patients enrolled in an open label retreatment extension study 6 months after their final
`treatment to achieve optimal correction. These subjects were followed for safety for 3 months
`following treatment. The safety profile observed during the I and 3 month follow-up was similar
`to that described above in the pivotal study.
`
`CLINICAL TRIALS
`
`A. I. U.S. Pivotal Study
`
`A. Study Design
`The safety and effectiveness of CTA for the treatment of facial wrinkles and folds was evaluated
`in a prospective, randomized, controlled, paired, double-blinded, multi-center, pivotal clinical
`study. Subjects underwent treatment with CTA in one NLF and control implant (Cosmoplast
`human collagen) in the contralateral NLF.
`
`Up to three bilateral treatments (i.e., initial treatment and up to 2 touch-up treatments),
`approximately 2 weeks apart, were allowed. At 2 and 4 weeks after each treatment, a Blinded
`Evaluator assessed the level of correction. If correction was less than optimal after the first or
`
`Page 4 of 8
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`

`

`CONFIDENTIAL
`
`CTA Commercial U.S. Package Insert
`Revision Date: 10/12/06
`second treatment, the Investigator re-treated the under-corrected NLFs using the same respective
`treatment materials as in the initial treatment. The Blinded evaluator and subject remained
`blinded to the randomized treatment assignment.
`Routine follow-up visits for safety and effectiveness occurred at 2 weeks after each treatment and
`at 1, 4, 6, 9 and 12 months after the last treatment. The Blinded reviewer and subject
`independently evaluated the severity of the subjects NLF using a validated 6-point wrinkle
`severity scale (ranging from 0 = no wrinkles to 5- very deep wrinkle, redundant fold).
`
`B. Study Endpoints
`The primary effectiveness endpoint was the blinded evaluator's Lemperle Rating Scale (LRS)
`score at 6-months following the last touch-up (at which optimal correction was achieved).
`Secondary effectiveness endpoints included: blinded evaluator LRS at 1- and 4-months; subject
`LRS at 1-, 4- and 6-months; proportion of nasolabial folds returning to baseline at 6-months;
`number of treatment sessions and volume of material to obtain optimal correction. The primary
`endpoint, the LRS score, is a 6-point scale. A change in LRS of I was considered to be clinically
`significant. Optimal correction was defined to be the best possible cosmetically pleasing result
`and 100% correction; unlimited touch-ups were permitted to achieve optimal correction.
`
`C. Study Population
`A total of 191 subjects (30 to 77 years of age) were randomized and treated and 185 (96.9%)
`completed the 6 month follow-up period. Demographics are outlined in Table 4.
`
`Table 4: Study Population Demographics
`
`Demographic
`Total study enrollment (randomized
`Age (mean ± standard deviation)
`Gender
`Male
`Female
`Race
`Caucasian
`Black or African-American
`Asian
`Other
`Ethnicity
`His anic or Latino
`Not Hispanic or Latino
`
`N (%)
`191 (100%)
`52.6 ±8.55
`
`16 (8.4%)
`175 (91.6%)
`
`172 (90.1%)
`7 3.7%0
`4 (2.1%)
`8 (4.2%
`
`18 (9.4%)
`173 90.8%
`
`D. Treatment Material Delivered
`The mean total volume injected per nasolabial fold for all treatment sessions (initial and touch-
`ups) was 1.2 mL for the CTA side and 1.9 mL for the Cosmoplast® side (control). Forty-seven
`(47) CTA sides (24.6%) required one or more touch-ups, whereas 61 (31.9%) of Cosmoplast®
`sides required one or more touch-ups. No randomized CTA NLF and two control-treated NLFs
`required three touch ups.
`
`E. Effectiveness Results
`The primary effectiveness results for CTA based on the Blinded Evaluator assessment of NLF
`severity at 6 months are presented in Table 5.
`
`Page 5 of 8
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`

`

`CTA Commercial U.S. Package Insert
`Revision Date: 10112/06
`
`CONFIDENTIAL
`
`Timepoint
`Pretreatment
`Optimal
`Correction
`4-Months
`6-Months
`
`Table 5: Mean Blinded Evaluator LRS Scores
`
`N
`191
`188
`
`CTA
`3.5
`I.1
`
`Cosmoplast®
`3.5
`1.1
`
`P-Value*
`0.8733
`0.2586
`
`175
`2.2
`2.7
`<0.0001
`182
`2.7
`0.0001
`3.0
`* p-values are from a paired comparison using McNemar's test.
`The blinded evaluator LRS scores demonstrated non-inferiority of CTA to Cosmoplast.
`
`Antibody Testing
`
`A pre-existing antibody response against CTA was observed in 5/208 (2.4%) subjects and
`18/208 (8.7%) subjects developed a response after CTA injection. 6/18(33%) subjects
`with elevated anti-CTA titers post-treatment experienced adverse events at the injection
`site that were judged related to device administration. This proportion of adverse events
`is similar to that observed in the entire CTA population 59/208 (27.7%.) While most
`reactions were mild in severity, one severe case of swelling and one severe case of
`inflammation were reported.
`
`HOW SUPPLIED
`CTA® is supplied in a single-use glass syringe with a luer-lock fitting. The product is presented
`as a sterile, non-pyrogenic gel in a 1.0 mL syringe. Fill volume varies by presentation and is
`stated on the syringe label and carton. A rubber cap is provided on the syringe tip to prevent
`leakage and protect sterility of the product. The CTA syringe components contain no latex. One
`30 G. x 'A" sterile needle is co-packaged with each syringe of CTA. Two patient record labels are
`provided.
`
`DIRECTIONS FOR USE
`Assembly of Needle to Syringe
`For safe use of CTA, it is important that the needle is properly assembled onto the syringe. Use
`the 30 G. x ½A" needle provided.
`1. Carefully unscrew the syringe tip cap while securely holding the syringe Luer adapter.
`2. With a loose grip on the narrow part of the needle shield, mount the needle on the luer-
`syringe lock by screwing clockwise until counterpressure is felt.
`3. With a firm grip on the wider part of the needle shield, press and turn the needle further
`until secure (approximately a quarter turn).
`4. Remove the needle shield by pulling the shield straight away from the syringe, ensuring
`not to twist the shield during removal.
`
`Injection of CTA
`I. Prior to injection, counsel the patient regarding the appropriate indications, risks, benefits
`and expected responses to CTA treatment. Advise the patient of necessary precautions
`and that touch-ups may be required to achieve and maintain optimal correction.
`2. Assess the patient's need for pain management and provide anesthetic per standard of
`care.
`3. Clean the area to be treated with suitable antiseptic solution.
`
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`CTA Commercial U.S. Package Insert
`Revision Date: 10/12/06
`
`CONFIDENTIAL
`
`5.
`
`4. Before injecting the patient, depress the syringe plunger until a droplet of CTA is visible
`at the tip of the needle.
`Insert the needle at an angle of approximately 300 parallel to the length of the wrinkle or
`fold. The bevel of the needle should face upwards, and CTA should be injected into the
`mid to deep dermis. This can be ascertained by observing a subtle elevation of the defect
`without any blanching following injection. If CTA is injected too deep or
`intramuscularly, the duration of effect may be shorter.
`6. Inject CTA applying even pressure on the plunger rod while slowly pulling the needle
`backwards. The wrinkle should be lifted and eliminated by the end of the injection. It is
`important that injection be stopped just before the needle bevel is pulled out of the skin to
`prevent material from leaking out or being placed too superficially in the skin.
`7. The defect should not be overcorrected but filled such that the contour depression is at
`the level of the surrounding skin (i.e., almost 100% correction). Do not overcorrect.
`With dermal contour deformities, the best results are obtained if the defect can be
`manually stretched to the point where the deformity is eliminated. The degree and
`duration of correction depend on the character of the defect treated, tissue stress at the
`implant site, depth of the implant in the tissue and injection technique. Markedly
`indurated defects may be difficult to correct.
`8. Specific injection technique with regard to depth of injection and administered quantity
`of CTA may vary. The linear threading technique, serial puncture technique and a
`combination of the two have been used with success.
`9. When injection is completed, the treated site may be gently massaged so that it conforms
`to the contour of the surrounding tissues. If an overcorrection has occurred, massage the
`area firmly between your fingers or against underlying superficial bone to obtain optimal
`results. Excessive massage is not recommended.
`10. If "blanching" is observed on injection (i.e., the overlying skin turns a whitish color),
`injection should be stopped immediately and the area massaged until it returns to a
`normal color.
`11. If the wrinkle or fold needs further treatment, the same procedure should be repeated with
`several punctures of the skin until a satisfactory result is obtained. Additional treatment
`with CTA may be necessary to achieve desired correction. In patients who have
`localized swelling after injection, the degree of correction may be difficult to judge
`immediately after treatment. In this case, touch-up injections at 1-2 weeks after the initial
`treatment may be indicated.
`12. Typical material usage for each treatment session is less thani .5 mL per treatment site.
`13. Patients should be advised to apply ice intermittently to the treated sites for 24 hours after
`injection to minimize swelling.
`14. Patients may have mild to moderate injection site reactions, which typically resolve in a
`few days.
`
`CAUTION: Do not reshield needles. Recapping by hand is a hazardous practice and should be
`avoided. Discard used syringes and needles in approved sharps containers.
`
`PATIENT INSTRUCTIONS
`It is recommended that the following information be shared with patients:
`* To report an adverse reaction, phone Anika Therapeutics at 800-XXX-XXXX.
`* Within the first 24 hours after injection, patients should avoid strenuous exercise,
`extensive sun or heat exposure or alcoholic beverages. Exposure to any of these
`
`Page 7 of 8
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`

`

`CTA Commercial U.S. Package Insert
`Revision Date: 10/12/06
`
`CONFIDENTIAL
`
`conditions may cause temporary redness or darkening of needle puncture sites, swelling
`and/or itching at the injection sites.
`Make-up may be applied a few hours post-treatment if no complications are present (e.g.,
`open wounds, bleeding or infection).
`
`STORAGE
`• CTA should be stored refrigerated or at room temperature (2-25°C, 36-77°F). Do not
`freeze.
`* CTA is a gel without visible particulates. In the event that the contents of the syringe
`show signs of separation, do not use the syringe and notify Anika Therapeutics at XXX-
`xxx-xxxx.
`
`Manufactured and distributed by:
`Anika Therapeutics, Inc.
`236 West Cummings Park
`Woburn, Massachusetts USA 01801
`
`U.S. Patent 6,537,979 B1. U.S. Patent Pending US1O/743,557.
`
`© 2006 Anika Therapeutics, Inc.
`
`Page 8 of 8
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`

`CTA Product (Cosmetic Tissue Augmentation)
`Patient Information
`
`Review this brochure carefully before beginning your CTA treatment.
`
`The information in this brochure is not meant to replace information provided by your
`physician or healthcare provider. You should always ask your physician or healthcare
`provider about your actual diagnosis, treatment and care.
`
`What is CTA?
`CTA is new type of dermal filler that is used to correct facial wrinkles and folds. It is a
`gel of modified hyaluronic acid (HA). The HA in CTA is made from a fermented source.
`It is injectable and compatible with the skin. CTA is formulated with lidocaine, a local
`anesthetic, to provide pain relief at the injection site. Skin testing is not required. CTA
`is slowly absorbed by the body.
`
`What is CTA used for?
`CTA is use for correction of moderate to severe facial wrinkles and folds (such as the
`folds occurring around the mouth) by injection into the mid to deep dermis.
`
`Do the injections hurt?
`CTA contains lidocaine to reduce injection site pain. Lidocaine is similar to the
`anesthetics used in dental procedures. Your physician may also use other kinds of
`anesthesia. In general, patients may experience varying levels of discomfort. The
`majority of patients report that the discomfort is mild to moderate and goes away within a
`few hours or days.
`
`How does it work?
`Your physician will cleanse the area appropriately and inject CTA just below the skin
`surface using a very thin needle. CTA will remain where is injected and add volume to
`correct the wrinkle or fold.
`
`What is involved in CTA treatment?
`If you feel you are a candidate for this treatment, talk with your physician. He or she will
`help you decide if you are a candidate for CTA treatment. Your physician will determine
`the appropriate course of injections and any periodic touch ups in order to achieve and
`maintain your satisfaction with the result.
`
`Who should not use CTA?
`• Patients with severe allergies or history or presence of multiple severe allergies should
`not use CTA.
`* CTA is composed of hyaluronic acid, lidocaine, and may contain trace amounts of gram
`positive bacterial proteins. CTA is contraindicated for patients with a history of allergies
`to such material.
`* The safety of CTA for use during pregnancy, in patients who are breastfeeding
`and in patients under the age of 18 years has not been studied.
`
`CTA Patient Labeling
`
`Revision Date: 10/12/06
`
`Page 1 of4
`
`; 2
`
`

`

`* The safety of CTA has not been studied in patients with an increased chance of
`developing keloid formations and hypertrophic scarring.
`* CTA should be used with caution in patients on inmmuosuppressive therapy.
`* Patients taking medicines that can prolong bleeding, such as aspirin and non
`steroidal anti-inflammatory drugs, may experience increased bruising or bleeding
`at injection sites.
`
`What else should I know about CTA?
`* The safety and effectiveness of CTA for areas other than the nasolabial folds (the
`folds extending from the nose to the corners of the mouth) or for time periods
`longer than one year has not been established.
`* As with all injections, the injection of CTA carries a chance of infection.
`* Minimize exposure of the area to excessive sun, tanning lamps and extreme cold
`weather until any initial swelling and redness have resolved.
`If laser treatment, chemical peeling or a similar procedure is considered before or
`after treatment with CTA, there is a possible chance of an inflammatory reaction
`at the injection site.
`
`*
`
`How will I feel immediately after treatment?
`
`You may notice temporary redness, swelling, bumps, slight bruising and tenderness
`around the treatment sites. These are normal after hyaluronic acid injections.
`
`Most patients could return to non-strenuous activity following treatment. Avoid
`strenuous exercise, extensive sun or heat exposure and alcoholic beverages for the first 24
`hours after injection. These could cause temporary redness, swelling and itching.
`
`Is the product safe?
`Yes, for most people. CTA is highly purified and is not derived from animal or human
`tissues so it is free of animal proteins. This reduces the risk from any animal-based
`transmitted disease. People with certain conditions or allergies should not use the
`product (please see Who should not use CTA?). Your physician can help you
`determine if you are a good candidate.
`
`Were side effects reported during the initial treatment clinical trial?
`CTA was studied in 208 patients who were injected with CTA on one side of the mouth
`and collagen on the other. Swelling, redness, bumps, bruising and tenderness were the
`most common side effects noted by patients after injection of CTA. Most of these side
`effects went away on their own within a few days or a week. See Table 1 for the side
`effects as reported by the patients.
`
`CIA Patient Labeling
`
`Revision Date: 10/12/06
`
`Page 2 of 4
`
`

`

`Table 1: Maximum Intensity of Symptoms after Treatment, Patient Diary
`
`CTA Side
`N=208
`Total reporting symptoms
`~~N
`(%)
`131
`(63.0%)
`151
`(72.6%)
`181
`(87.0%)
`108
`(51.9%)
`145
`__9_7_%(69.7%)
`83
`(39.9%)
`129
`(62.0%)
`
`________
`Bruising
`
`Redness
`
`Swelling
`
`Pain
`
`Tenderness
`
`Itching
`
`Nodule
`formation
`
`Cosmoplast® Side
`N=191
`Total reporting symptoms
`N (%)
`94
`(49.2%)
`124
`(64.9%)
`129
`(67.5%)
`63
`(33.0%)
`101
`(52.9%)
`49
`(25.7%)
`112
`(58.6%)
`
`What are the potential concerns when using CTA?
`Complications such as prolonged redness or swelling, an open wound, hard lumps,
`abscess, bleeding or infection could occur.
`
`When should I notify my physician?
`Any side effects that last longer than a week should be reported to your physician. Call
`your physician if you are concerned about the side effects or think you have a
`complication.
`
`What should I do after treatment?
`Apply ice to the site for up to 15 minutes every hour or two for 24 hours after injection to
`minimize swelling and redness. You may need touch-ups to achieve and maintain
`optimal correction. Discuss pain management with your physician before the injections
`are performed.
`
`When may I apply make-up?
`You can apply make-up a few hours after treatment if there are no complications such as
`open wounds, bleeding or infection.
`
`How long does the correction last?
`After six months, 56% of the patients maintained benefit compared to their original
`appearance. However, the correction is temporary, and repeat injections are usually
`needed to maintain correction. Your results will depend upon your aging process, the
`extent of the wrinkle and even your physician.
`
`How often will I require treatment?
`CTA is absorbed into your body naturally over time. The correction will likely disappear
`as this happens. That is why you may need additional treatments but the amount and how
`many times will depend upon each individual. Typically patients may require treatment
`every 6-12 months.
`
`CTA Patient Labeling
`
`Revision Date:
`
`10/12/06
`
`Page 3 of 4
`
`25
`
`

`

`What are the risks of retreatinent?
`The same complications such as prolonged redness or swelling, an open wound, hard
`lumps, abscess, bleeding or infection could occur with retreatment as with initial
`treatment. There are no known additional risks associated with retreatment with CTA.
`
`Without touch-ups, how will my skin look?
`Without any additional touch ups, your skin will eventually look like it did before
`treatment, because the CTA will be absorbed into your body over time.
`
`What are my other options for treatment?
`There are a variety of dermal fillers available in the US. Prices, safety and effectiveness
`vary. Consult with your physician to determine which one is right for you.
`
`For more information, write or call:
`
`Anika Therapeutics, Inc.
`236 West Cummings Park
`Woburn, MA 0 1801 USA
`
`Toll-Free: 800-XXX-XXXX
`
`02006 Anika Therapeutics, Inc.
`
`CTA Patient Labeling
`
`Revision Date: 10/12/06
`
`Page 4 of 4
`
`