A Multicenter, Double-blind, Randomized, Controlled, Roll-over Retreatment Study of the Safety and Pain Associated With Injections of PN40082, RV001 With Topical Anesthetic or RV001 for Lip Augmentation
Condition: Lip Augmentation
Intervention: PN40082
Intervention description: 1.0 mL pre-filled syringes with 25 mg/mL of stabilized hyaluronic acid and lidocaine 0.3% w/w.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a multicenter, double-blind, randomized, controlled, roll-over retreatment clinical study of retreatment of subjects seeking lip augmentation who received treatment with either PN40082 or Restylane Silk in prior Protocol PRO 2018-02 (NCT04032977), and PN40082 in prior Protocol PRO 2018-03 (NCT04029519). Subjects meeting the inclusion/exclusion criteria will receive a single additional treatment with either RV001, RV001 with a topical anesthetic, or PN40082. The Evaluating Investigator will be blinded to the treatment. Injections of the study device will be performed by an unblinded Treating Investigator.
Masking: Double (Participant, Outcomes Assessor)
Masking description: Injections of the study device are performed by the unblinded Treating Investigator. The blinded Evaluating Investigator is not allowed to retrieve study supplies or to be present during opening of the study supplies or during the injections. The Treating Investigator is not to have any discussion with the Evaluating Investigator or subjects regarding the treatments.
Subjects are blinded to treatment assignment. Subjects are physically masked (blindfolded) just prior to and during all injection procedures to prevent observation of the syringes containing study device.
Subjects, investigators, the Sponsor's staff conducting the study, and members of the administrative team will not have access to individual subjects' treatment assignments. In the event of an emergency that requires breaking of the study blind, the randomization code will be maintained by each investigator that can be opened to reveal the study device.
Enrollment: 5.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to evaluate the safety of repeat injections and pain associated
      with injection of PN40082 and comparative pain associated with RV001 with a topical
      anesthetic and RV001 for lip augmentation.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Completed Protocol PRO 2018-03 OR Protocol PRO 2018-02 and did not enroll in Protocol
             PRO 2018-03.

          2. Men or non-pregnant or non-breastfeeding women over 21 years of age

          3. At PRO 2018-02 baseline visit had an overall score of very thin, or thin on the LFGS,
             as agreed upon by the Treating and Evaluating Investigators, and desires at least a
             1-point improvement in overall LFGS score; OR Had a Fitzpatrick skin phototype IV, V
             or VI and has an LFGS score of thick or full, as agreed upon by the Treating and
             Evaluating Investigators, and desires treatment to the vermilion body of 1 or both
             lips

          4. If female and of childbearing potential, a negative urine pregnancy test at Visit
             1/Day 1 and the subject agrees to use adequate contraception during the study period.

          5. Willing to give written informed consent.

        Exclusion Criteria:

          1. Women who are pregnant, lactating, or planning a pregnancy.

          2. Subjects with a known history of allergy, anaphylaxis or hypersensitivity to
             injectable hyaluronic acid products, local anesthetics of the amide type such as
             lidocaine, or to latex.

          3. Subjects with a significant ongoing adverse event from PRO 2018-02 or PRO 2018-03 that
             in the opinion of the investigator could be worsened by participation in this study.

          4. Subjects that experienced an SAE, AESI, visual changes or other serious medical
             conditions during PRO 2018-02 or PRO 2018-03

          5. Subjects who are unable to withhold thrombolytics, or inhibitors of platelet
             aggregation or nonsteroidal anti inflammatory drugs (NSAIDs, e.g., aspirin, ibuprofen)
             or other substances known to increase coagulation time (e.g., herbal supplements with
             garlic or gingko) within 10 days before AND after any injection session.

          6. Subjects with clinically significant organic disease including clinically significant
             cardiovascular, hepatic, pulmonary, neurologic, or renal disease or other medical
             condition, serious intercurrent illness, or extenuating circumstance that, in the
             opinion of the investigator, preclude participation in the trial.

          7. Subjects with lip tattoos, piercings, facial hair, or scars that would interfere with
             visualization of the lips and perioral area for the effectiveness assessments.

          8. Subjects with abnormal lip function, with inability to effectively sip water through a
             straw.

          9. Subjects with abnormal lip sensation with inability to feel a 0.4G monofilament or a
             cotton wisp at any site on the lip.

         10. Subjects with moderate or severe abnormal lip asymmetry.

         11. Subjects with any mass formation on the lip.

         12. Subjects with dentures or any device covering all or part of the upper palate, and/or
             severe malocclusion or dentofacial or maxillofacial deformities as judged by the
             Treating Investigator. Subjects planning to undergo extensive dental procedures such
             as dental implants, multiple tooth extractions, or oral surgery should not
             participate. Minor dental procedures such as teeth cleaning and repair of caries are
             not exclusionary.

         13. Subjects that have undergone facial plastic surgery or received permanent facial
             implants (e.g., polymethylmethacrylate, silicone, polytetrafluoroethylene,
             polyacrylamide, lifting threads) anywhere in the face or neck, or are planning to be
             implanted with any of these products during the study.

         14. Subjects that have undergone semi-permanent dermal filler treatment (e.g., calcium
             hydroxylapatite, poly-L-lactic acid) in the lower face (below the orbital rim) within
             12 months before enrollment or are planning to undergo such treatment during the
             study.

         15. Subjects that have undergone facial tissue augmentation with fat injections, botulinum
             toxin injections in the lower face (below the orbital rim), mesotherapy, or cosmetic
             procedures in the face or neck (e.g., face-lift, laser, photo-modulation, intense
             pulsed light, radio frequency, dermabrasion, moderate or greater depth chemical peel,
             microneedling, or other ablative procedures) within 9 months before enrollment or are
             planning to undergo any of these procedures during the study.

         16. that have used ANY lip filling agents within 12 months of study enrollment (hyaluronic
             acid products, collagen-based products, etc.) other than Investigational Device
             administered in PRO 2018-02 and PRO-2018-03.

         17. Subjects that have used any lip plumping products or devices within 10 days before
             enrollment or are planning to use such products during the study.

         18. Subjects that have begun using any over-the-counter (OTC) or prescription oral or
             topical anti wrinkle products for the lips or around the mouth within 90 days before
             enrollment or are planning to begin using such products during the study (Subjects who
             have been on a stable regimen of such products for at least 90 days are eligible for
             the study and must continue their regimen throughout the study).

         19. Subjects that have a history or presence of bleeding disorders.

         20. Subjects that have used systemic corticosteroids or immunosuppressive medications
             within 30 days prior to treatment.

         21. Subjects that are on a concurrent regimen of lidocaine or structurally related local
             anesthetics (e.g., bupivacaine)

         22. Subjects that have an active inflammation (skin eruptions such as cysts, pimples,
             rashes, or hives), infection cancerous or precancerous lesion, or unhealed wound on
             the face.

         23. Subjects that have a history of known susceptibility to keloid formation or
             hypertrophic scars.

         24. Subjects that have porphyria.

         25. Subjects that have active herpes labialias lesions at the time of injections. Subjects
             with a history of herpes labialis who have had four (4) or more outbreaks in the 12
             months prior to enrollment are also excluded even in the absence of lesions at the
             baseline visit.

         26. Subjects that have impaired cardiac conduction, severely impaired hepatic function, or
             severe renal dysfunction that, in the opinion of the investigator, would place them at
             risk of associated complications from these illnesses during the course of the study.

         27. Subjects that have any uncontrolled disease, i.e., a condition that has not been
             appropriately diagnosed, evaluated, and received medically appropriate treatment or
             care

         28. Subjects that have severe cardiovascular disease; examples include but are not limited
             to New York Heart Association heart failure classification III or IV, unstable angina,
             and internal pacemakers. Potential subjects with other significant cardiovascular
             diseases should be discussed with the Medical Monitor before enrolling.

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