Lip Augmentation
Conditions
Brief summary
To compare the safety and efficacy profile of PN40082 versus Restylane Silk Injectable Gel with 0.3% lidocaine (Restylane Silk) for lip augmentation in approximately 158 subjects.
Detailed description
The objective of the study is to compare the safety and efficacy profile of PN40082 versus Restylane Silk Injectable Gel with 0.3% lidocaine (Restylane Silk) for lip augmentation. Approximately 158 subjects will be randomized at approximately 7 sites in this is a double-blind, randomized, controlled, multicenter clinical study of subjects seeking lip augmentation. Subjects meeting inclusion/exclusion criteria will be randomized 1:1 to treatment with either PN40082 or Restylane Silk. The Evaluating Investigator will be blinded to the treatment. Injections of the study device will be performed by an unblinded Treating Investigator. At each visit, the blinded Evaluating Investigator evaluations and subject evaluations of the treated areas will be performed and recorded. Visits and telephone contacts will occur at: Visit 1 / Week 0 (Day 1) - baseline and treatment * Day 3 (±2 days) - Safety follow-up telephone call * Day 14 (±2 days) - Safety follow-up telephone call Visit 2 / Day 28 (±2 days) / Month 1 - interim visit (touch-up if necessary) * Day 33 (±2 days) - Safety follow-up telephone call (for subjects with touch-up treatment * Day 44 (±2 days) - Safety follow-up telephone call (for subjects with touch-up treatment) Visit 3 / Day 56 (±4 days) / Month 2 - interim visit Visit 4 / Day 84 (±4 days) / Month 3 - interim visit * Day 112 (±4 days) / Month 4 - Safety follow-up telephone call * Day 140 (±4 days) / Month 5 - Safety follow-up telephone call Visit 5 / Day 168 (±7 days) / Month 6 - End of Study (EOS) Visit. All subjects will undergo the consent procedure for the open label retreatment protocol. Evaluations include: Lip Fullness Grading Scale (LFGS) (Overall lip fullness considering both lips together, fullness of the upper lip and fullness of the lower lip) Perioral lines at rest severity scale (POL) (Overall perioral lines at rest severity considering both lips together, perioral lines at rest severity of the upper lip and perioral lines at rest severity of the lower lip) Patient Global Aesthetic Improvement (pGAI) Investigator Global Aesthetic Improvement (iGAI) Safety will be assessed by monitoring adverse events (AEs) at all study visits Other Safety Evaluations include: Lip Function Lip Sensation Other evaluations include: Investigator Ease of Use Assessment Swelling Assessment Subject Satisfaction with Lips Assessment Subjects participation will be approximately 6 months and the study is estimated to last 20 months from first subject first visit to last subject last visit.
Interventions
DEVICEPN40082
To provide a 1-point improvement in the lip fullness grading scale score of subjects with very thin or thin lips or subjects with Fitzpatrick IV, V or VI to improve the LFGS score by 1 for 1 or both lips
DEVICERestylane Silk
To provide a 1-point improvement in the lip fullness grading scale score of subjects with very thin or thin lips or subjects with Fitzpatrick IV, V or VI to improve the LFGS score by 1 for 1 or both lips
Sponsors
Symbio, LLC
Prollenium Medical Technologies Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Only the unblinded treating investigator and unblinded assistant will be unblinded to the treatment. The remainder of study/site personnel remain blinded.
Intervention model description
Double-blind, randomized, controlled, multicenter clinical study
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Men or non-pregnant or non-breastfeeding women over 21 years of age 2. If female and of childbearing potential, a negative urine pregnancy test at Baseline (Day 1) and the subject agrees to use adequate contraception during the study period 3. Has 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 Has 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. Willing to give written informed consent
Exclusion criteria
1. Women who are pregnant, lactating, or planning a pregnancy 2. History of allergy, anaphylaxis or hypersensitivity to injectable hyaluronic acid products, local anesthetics of the amide type such as lidocaine, or to latex, or is planning to undergo desensitization therapy during the study 3. Has lip tattoos, piercings, facial hair, or scars that would interfere with visualization of the lips and perioral area for the effectiveness assessments 4. Has abnormal lip function, with inability to effectively sip water through a straw 5. Has abnormal lip sensation, with inability to feel a 0.4G monofilament or a cotton wisp at any site on the lip 6. Has moderate or severe abnormal lip asymmetry 7. Has any mass formation on the lip 8. Has 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 9. Has undergone facial plastic surgery or received permanent facial implants (e.g., polymethylmethacrylate, silicone, polytetrafluoroethylene, polyacrylamide, lifting threads) anywhere in the face or neck, or is planning to be implanted with any of these products during the study 10. Has 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 is planning to undergo such treatment during the study 11. Has 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 is planning to undergo any of these procedures during the study 12. Has used ANY lip filling agents within 12 months of study enrollment (hyaluronic acid products, collagen-based products, etc.) 13. Has used any lip plumping products or devices within 10 days before enrollment or is planning to use such products during the study 14. Has 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 is 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.) 15. Is on an ongoing regimen of anticoagulation therapy (e.g., warfarin), 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 of undergoing study device injections. Subjects who will withhold such therapy for 10 days before AND after any injection session may participate 16. Has a history or presence of bleeding disorders 17. Has used systemic corticosteroids or immunosuppressive medications within 30 days prior to treatment 18. Is on a concurrent regimen of lidocaine or structurally related local anesthetics (e.g., bupivacaine) 19. Has an active inflammation (skin eruptions such as cysts, pimples, rashes, or hives), infection, cancerous or precancerous lesion, or unhealed wound on the face 20. Has a history of known susceptibility to keloid formation or hypertrophic scars 21. Has porphyria 22. Has active herpes labialis 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 23. Has 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 24. Has any uncontrolled disease, i.e., a condition that has not been appropriately diagnosed, evaluated, and received medically appropriate treatment or care 25. Has 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-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Overall Lip Fullness Grading Scale | Visit 1 baseline to Visit 3 Month 2, 56 days | The Lip Fullness Grading Scale is a 5 point photonumeric rating scale with 0 being very thin lips (worse outcome) up to 4 being full lips (better outcome) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Success Lip Fullness Grading Scale | Visit 1 baseline to Visit 3 Month 2, 56 days | Percent of subjects with Lip Fullness treatment success (responder: overall LFGS based on the Blinded Evaluating Investigator Assessment) at Visit 3/Month 2 where responder is defined as a subject with at least a 1-grade increase from baseline on the LFGS post augmentation The lip fullness grading scale is a 5 point photonumeric rating scale with 0 being very thin lips (worse outcome) to 4 being full lips (better outcome) |
| Treatment Success Perioral Lines Severity Scale | Visit 1 baseline to Visit 4 Month 3, 84 days | Percent of responders with Perioral Lines Treatment Success overall on the POL severity scale at Visit 4/Month 3 (defined as a subject demonstrating ≥ 1-point improvement, i.e., decrease in severity, from baseline. The Perioral Lines at rest severity scale is a 4 point rating scale with 0 = None, a mouth with no perioral lines (better outcome) to 3 = Severe, being a mouth with many deep lines or crevices (worse outcome) |
| Change From Baseline to Visit 4/Month 3 in Overall Lip Fullness Grading Scale | Visit 1 baseline to Visit 4 Month 3, 84 days | The lip fullness grading scale is a 5 point photonumeric rating scale with 0 being very thin lips (worse outcome) to 4 being full lips (better outcome) |
| Change From Baseline to Visit 5/Month 6 in Overall Lip Fullness Grading Scale | Visit 1 baseline to Visit 5 Month 6, 168 days | The lip fullness grading scale is a 5 point photonumeric rating scale with 0 being very thin lips (worse outcome) to 4 being full lips (better outcome) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PN40082 Test device: PN40082 (manufactured by Prollenium Medical Technologies) is a clear, colorless gel in 1.0 mL pre-filled syringes with 25 mg/mL of stabilized hyaluronic acid and lidocaine 0.3% w/w | 80 |
| Restylane Silk Restylane Silk (manufactured by Q-Med AB for Medicis - A Division of Valeant Pharmaceuticals Corporation North America, LLC ) is a clear, colorless gel in 1.0 mL pre-filled syringes formulated to a concentration of 20 mg/mL of stabilized hyaluronic acid and lidocaine 0.3% w/w. | 78 |
| Total | 158 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 7 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 1 |
Baseline characteristics
| Characteristic | Restylane Silk | Total | PN40082 |
|---|---|---|---|
| Age, Continuous | 49.2 years STANDARD_DEVIATION 11.85 | 47.4 years STANDARD_DEVIATION 11.94 | 45.6 years STANDARD_DEVIATION 11.85 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 44 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 60 Participants | 114 Participants | 54 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 27 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 61 Participants | 126 Participants | 65 Participants |
| Sex: Female, Male Female | 76 Participants | 156 Participants | 80 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 80 | 0 / 78 |
| other Total, other adverse events | 75 / 80 | 75 / 78 |
| serious Total, serious adverse events | 2 / 80 | 1 / 78 |
Outcome results
Primary
Change in Overall Lip Fullness Grading Scale
The Lip Fullness Grading Scale is a 5 point photonumeric rating scale with 0 being very thin lips (worse outcome) up to 4 being full lips (better outcome)
Time frame: Visit 1 baseline to Visit 3 Month 2, 56 days
Population: Per-Protocol population is all randomized subjects who met all inclusion/exclusion criteria; received study device, completed Visit 5 within the specified window; had LFGS score by the Blinded Evaluating Investigator at Visit 3/Month 2 within the specified visit window, and had no significant protocol violations that would affect the treatment evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PN40082 | Change in Overall Lip Fullness Grading Scale | 1.52 score on a scale | Standard Deviation 0.885 |
| Restylane Silk | Change in Overall Lip Fullness Grading Scale | 1.53 score on a scale | Standard Deviation 0.79 |
Secondary
Change From Baseline to Visit 4/Month 3 in Overall Lip Fullness Grading Scale
The lip fullness grading scale is a 5 point photonumeric rating scale with 0 being very thin lips (worse outcome) to 4 being full lips (better outcome)
Time frame: Visit 1 baseline to Visit 4 Month 3, 84 days
Population: Per-protocol population is all randomized subjects who met all inclusion/exclusion criteria; received study device, completed Visit 5 within the specified window; had LFGS score by the Blinded Evaluating Investigator at Visit 3/Month 2 within the specified visit window, and had no significant protocol violations that would affect the treatment evaluation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PN40082 | Change From Baseline to Visit 4/Month 3 in Overall Lip Fullness Grading Scale | 1.37 score on a scale | Standard Deviation 0.917 |
| Restylane Silk | Change From Baseline to Visit 4/Month 3 in Overall Lip Fullness Grading Scale | 1.42 score on a scale | Standard Deviation 0.712 |
Secondary
Change From Baseline to Visit 5/Month 6 in Overall Lip Fullness Grading Scale
The lip fullness grading scale is a 5 point photonumeric rating scale with 0 being very thin lips (worse outcome) to 4 being full lips (better outcome)
Time frame: Visit 1 baseline to Visit 5 Month 6, 168 days
Population: Per-protocol population is all randomized subjects who met all inclusion/exclusion criteria; received study device, completed Visit 5 within the specified window; had LFGS score by the Blinded Evaluating Investigator at Visit 3/Month 2 within the specified visit window, and had no significant protocol violations that would affect the treatment evaluation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PN40082 | Change From Baseline to Visit 5/Month 6 in Overall Lip Fullness Grading Scale | 1.00 score on a scale | Standard Deviation 0.727 |
| Restylane Silk | Change From Baseline to Visit 5/Month 6 in Overall Lip Fullness Grading Scale | .93 score on a scale | Standard Deviation 0.634 |
Secondary
Treatment Success Lip Fullness Grading Scale
Percent of subjects with Lip Fullness treatment success (responder: overall LFGS based on the Blinded Evaluating Investigator Assessment) at Visit 3/Month 2 where responder is defined as a subject with at least a 1-grade increase from baseline on the LFGS post augmentation The lip fullness grading scale is a 5 point photonumeric rating scale with 0 being very thin lips (worse outcome) to 4 being full lips (better outcome)
Time frame: Visit 1 baseline to Visit 3 Month 2, 56 days
Population: Per-protocol population is all randomized subjects who met all inclusion/exclusion criteria; received study device, completed Visit 5 within the specified window; had LFGS score by the Blinded Evaluating Investigator at Visit 3/Month 2 within the specified visit window, and had no significant protocol violations that would affect the treatment evaluation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PN40082 | Treatment Success Lip Fullness Grading Scale | 49 Participants |
| Restylane Silk | Treatment Success Lip Fullness Grading Scale | 51 Participants |
Secondary
Treatment Success Perioral Lines Severity Scale
Percent of responders with Perioral Lines Treatment Success overall on the POL severity scale at Visit 4/Month 3 (defined as a subject demonstrating ≥ 1-point improvement, i.e., decrease in severity, from baseline. The Perioral Lines at rest severity scale is a 4 point rating scale with 0 = None, a mouth with no perioral lines (better outcome) to 3 = Severe, being a mouth with many deep lines or crevices (worse outcome)
Time frame: Visit 1 baseline to Visit 4 Month 3, 84 days
Population: Per Protocol population is all randomized subjects who met all inclusion/exclusion criteria; received study device, completed Visit 5 within the specified window; had LFGS score by the Blinded Evaluating Investigator at Visit 3/Month 2 within the specified visit window, and had no significant protocol violations that would affect the treatment evaluation. Of the per protocol population the subjects who had perioral injection at Visit 1 or Visit 2 and had POL assessed at Visit 4/Month 3
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PN40082 | Treatment Success Perioral Lines Severity Scale | 14 Participants |
| Restylane Silk | Treatment Success Perioral Lines Severity Scale | 12 Participants |