Clinical trial NCT02736825: Simulines Non-Inferiority Pivotal Study
Official title: Non-Inferiority Study of the Safety and Efficacy of Ultherapy® Using Standard Versus Simulines Transducers at a Reduced Energy Level for Patient Comfort
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Skin Laxity
Lead sponsor: Merz North America, Inc.
Sponsor class: INDUSTRY
First posted: 2016-04-13
Enrollment: 262
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Up to 260 subjects presenting with skin laxity on the face and neck will be randomized to one of two treatment groups. Subjects meeting all entrance criteria will receive study treatment, then complete two post treatment phone contacts and follow-up study visits at 90, 180 and 365 days post treatment. Study images will be obtained pre-treatment, immediately post-treatment, and at each follow-up visit for qualitative and quantitative assessments of efficacy.

Detailed description: This is a prospective, randomized, double blinded, multi-center, parallel arm, non-inferiority, pivotal clinical trial to demonstrate the efficacy of the Ultherapy treatment with prototype 2 simulines transducers (4-3.0 Smm and 4-4.5 Smm) at energy level (EL) 2 is non-inferior to treatment with standard transducers (7-3.0 mm and 4-4.5mm) at EL 2 for lifting the lower face and neck and to demonstrate the safety of treatment with prototype 2 simulines transducers is similar to treatment with standard transducers.

Changes from baseline in quantitative measures of neck and submental lift will be assessed at study follow-up visits. Global Aesthetic Improvement Scale scores, Merz Jawline Grading Scale scores, 3D volumetric changes from baseline to post treatment, patient satisfaction and patient-reported improvement will be obtained.

Eligibility criteria: Inclusion Criteria:

* Male or female, age 30 to 70 years.
* Subject in good health.
* Body Mass Index (BMI) of ≤30.
* Skin laxity in the area(s) to be treated as determined by trained physician assessors.
* Willingness to avoid excessive or prolonged exposure to sunlight, tanning booths, sun lamps, or ultraviolet (UV) light sources.
* Willingness to apply study provided sunscreen (Neocutis Micro-Day Rejuvenating Cream) daily until study exit to help limit sun exposure.
* Willingness to avoid or periodically stop use of Sunless Tanners (washout period of two weeks prior to each study visit is required).
* Understands and accepts the obligation not to undergo any other procedures in the areas to be treated through the follow-up period
* Willingness to avoid non-emergent dental procedures in the 3 weeks prior to/ post treatment.
* Willingness and ability to comply with protocol requirements, including returning for follow-up visits and abstaining from exclusionary procedures for the duration of the study.
* Subjects of childbearing potential must have a negative urine pregnancy test result and must not be lactating at the Screening Visit and be willing and able to use an acceptable method of birth control (e.g. barrier methods used with a spermicidal agent, hormonal methods, intrauterine device (IUD), surgical sterilization, abstinence) during the study. Women will not be considered of childbearing potential if one of the following conditions is documented on the medical history:

  a. Postmenopausal for at least 12 months prior to study; b. Without a uterus and/or both ovaries; or c. Bilateral tubal ligation at least six months prior to study enrollment.
* Absence of physical or psychological conditions unacceptable to the investigator.
* Willingness to refrain from use of aspirin, Ibuprofen, Naproxen or any other non-steroidal anti-inflammatory drug (NSAID) prior to study treatment and chronic use during the entire post-treatment study period. Washout period, if chronic user, for 4 weeks prior to the study treatment. After study treatment is completed, limited acute NSAID use, i.e., a maximum of 2-3 doses in any 2 week period, is allowed if needed.
* Willingness and ability to provide written consent for study-required photography and adherence to photography procedures (i.e., removal of jewelry and makeup).
* Willingness and ability to provide written informed consent and HIPAA authorization prior to performance of any study-related procedure.

Exclusion Criteria:

* Presence of an active systemic or local skin disease that may affect wound healing.
* History of Bell's Palsy.
* History of chronic or frequently recurring episodic (recurrent episode in past 12 months) autoimmune diseases such as Multiple Sclerosis, Crohn's Disease, Psoriasis, Myasthenia Gravis, Lambert-Eaton Syndrome that has required immune suppressant therapy (such as biologic drug or corticosteroid treatment).
* Palpable thyroid lesion, lymphadenopathy, or other pathological changes within the treatment area.
* History of skin cancer in the areas to be treated, basal cell nevus syndrome, or jaw cysts.
* Known allergy or sensitivity to Ibuprofen.
* Severe solar elastosis.
* BMI \> 30.
* Significant changes in weight (e.g. more than 5 pounds) over the past 6 months or anticipated significant changes in weight or diet over the course of the study.
* Pregnant within the past year.
* Excessive subcutaneous fat in the area(s) to be treated.
* Excessive skin laxity in the area(s) to be treated as determined by trained physician assessors.
* Significant scarring in the area(s) to be treated that would interfere with assessing results.
* Open wounds or lesions in the area(s) to be treated.
* Severe or cystic acne on the area(s) to be treated.
* Active implants (e.g., pacemakers or defibrillators), or metallic implants in the treatment areas (dental implants not included).
* Inability to understand the protocol or to give informed consent.
* Microdermabrasion, or prescription level glycolic acid treatment to the treatment area(s) within two weeks prior to study participation or during the study.
* Marked asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, or thick sebaceous skin in the area(s) to be treated.
* History of chronic drug or alcohol abuse.
* Concurrent therapy that, in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of the study device.
* Subjects who anticipate the need for surgery or overnight hospitalization during the study.
* Subjects who, in the investigator's opinion, have a history of poor cooperation, noncompliance with medical treatment, or unreliability.
* Concurrent enrollment in any study involving the use of investigational devices or drugs.
* Current smoker or history of smoking in the last five years.
* Current user of any nicotine-containing products, e.g., e-cigarettes, Nicorette gum, nicotine patches, etc.
* History of the following cosmetic treatments in the area(s) to be treated:

  1. Any energy based device (radio-frequency (RF), micro-focused ultrasound (MFU), etc.) procedure for skin tightening within the past year;
  2. Injectable filler of any type within the past:

  i. 12 months for Hyaluronic acid fillers (e.g. Restylane)

ii. 12 months for Ca Hydroxylapatite fillers (e.g. Radiesse)

iii. 24 months for Long Lasting Hyaluronic acid (e.g. Voluma) and Poly-L-Lactic acid fillers (e.g. Sculptra)

iv. Ever for permanent fillers (e.g. Silicone, ArteFill)

c. Neurotoxins within the past six months (neuromodulators are allowed in the glabella and forehead, not allowed in the temples, crow's fee or anywhere below the lateral canthus);

d. Fractional and fully ablative resurfacing laser treatment within the past two years;

e. Nonablative, rejuvenative laser or light treatment within the past six months;

f. Surgical dermabrasion or deep facial peels within the past two years;

g. Facelifts, neck surgery (e.g. thyroid, neck lifts, neck liposuction, etc.) within the past two years;

h. Micro needling within the past year;

i. Kybella, Coolsculpting, or Mesotherapy within the past two years; or

j. Any history of contour threads.

* History (in the prior year) or current use of the following prescription medications:

  1. Accutane or other systemic retinoids within the past six months;
  2. Initiation of topical retinoids within the past 6 months or throughout the course of the study;
  3. Antiplatelet agents/Anticoagulants (Coumadin, Heparin, Plavix);
  4. Systemic steroids including prednisone;
  5. Dermal regulators of collagen;
  6. Initiation of bioidentical hormones or human growth hormone (HGH) within the past 6 months or throughout the course of the study; or
  7. Psychiatric drugs that in the investigators opinion would impair the subject from understanding the protocol requirements or understanding and signing the informed consent.

Primary outcomes:
measure: Number of Participants Who Achieved Greater Than or Equal to (>=) 20 mm^2 Reduction in Submental Area at Day 90
timeFrame: Day 90
Secondary outcomes:
measure: Number of Participants Who Achieved >=20 mm^2 Reduction in Submental Area at Day 180
timeFrame: Day 180
measure: Number of Participants Who Achieved >=20 mm^2 Reduction in Submental Area at Day 365
timeFrame: Day 365
measure: Number of Participants Who Showed Improvement in Overall Lifting and Tightening of Skin at Day 90
timeFrame: Day 90
measure: Number of Participants Who Showed Improvement in Overall Lifting and Tightening of Skin at Day 180
timeFrame: Day 180
measure: Number of Participants Who Showed Improvement in Overall Lifting and Tightening of Skin at Day 365
timeFrame: Day 365
measure: Percent Change From Baseline in Volume as Assessed by Quantificare 3 D Imaging System at Day 90
timeFrame: Day 90
measure: Percent Change From Baseline in Volume as Assessed by Quantificare 3D Imaging System at Day 180
timeFrame: Day 180
measure: Percent Change From Baseline in Volume as Assessed by Quantificare 3D Imaging System at Day 365
timeFrame: Day 365
measure: Number of Participants With Some Level of Improvement and Satisfaction on Day 90
timeFrame: Day 90
measure: Mean Treatment Times
timeFrame: Baseline
measure: Mean Pain Scores to Assess Participant's Treatment Related Comfort Level Based on Numeric Rating Scale (NRS)
timeFrame: Baseline
measure: Number of Participants With Overall Aesthetic Improvement as Assessed by Subject Global Aesthetic Improvement Scale (SGAIS) at Day 90
timeFrame: Day 90
measure: Number of Participants With Overall Aesthetic Improvement as Assessed by SGAIS at Day 180
timeFrame: Day 180
measure: Number of Participants With Overall Aesthetic Improvement as Assessed by SGAIS at Day 365
timeFrame: Day 365
measure: Number of Participants With Overall Aesthetic Improvement as Assessed by Clinician Global Aesthetic Improvement Scale (CGAIS) at Day 90
timeFrame: Day 90
measure: Number of Participants With Overall Aesthetic Improvement as Assessed by CGAIS at Day 180
timeFrame: Day 180
measure: Number of Participants With Overall Aesthetic Improvement as Assessed by CGAIS at Day 365
timeFrame: Day 365
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Clinical Testing of Beverly Hills
state: California
city: Roseville
country: United States
facility: Roseville Facial Plastic Surgery
state: California
city: Sacramento
country: United States
facility: Laser and Skin Surgery Center
state: California
city: San Diego
country: United States
facility: Dermatology Cosmetic Laser Medical Associates of La Jolla
state: California
city: Greenwood Village
country: United States
facility: AboutSkin Dermatology
state: Colorado
city: Cockeysville
country: United States
facility: Maryland Laser Skin and Vein Dermatology
state: Maryland
city: Wilmington
country: United States
facility: Wilmington Dermatology Center
state: North Carolina
city: Spokane
country: United States
facility: Premier Clinical Research
state: Washington
Study officials:
affiliation: Ulthera, Inc
name: Kari Larson, MBA
role: STUDY_DIRECTOR
References: