Efficacy of a Topical Anesthetic Containing Lidocaine and Prilocaine in Treatment With CO2 Fractional Laser
Condition: Lidocaine Adverse Reaction; Prilocaine Adverse Reaction
Study type: Interventional
Phase: Phase 3

Summary: 
      This is a study aimed at evaluating the efficacy of a topical anesthesia (test product)
      compared to placebo in adult patients of phototypes I to III, with indication of treatment of
      CO2 fractional laser in the forehead. In addition to efficacy, safety and tolerability of the
      product have been studied.

      The product under investigation is a topical formulation containing lidocaine 25 mg/g and
      prilocaine 25mg/g which in previous studies performed in the same institution with healthy
      subjects in adulthood showed faster onset than other formulations. In these previous studies,
      the product was well tolerated, and there were no signs of a skin reaction or adverse events
      of a systemic nature.

      The CO2 fractional laser treatment is routinely used by plastic surgery and dermatology for
      treatment with aesthetic purposes of skin imperfections. It's a procedure until certain
      painful point, which as a rule is performed without prior use of topical anesthetic.

      The test product is believed to produce a clinically significant reduction of pain when
      compared to placebo, during the application of CO2 laser on the forehead for the aesthetic
      treatment of the face.
    

Detailed description: 
      The study was designed to allow assessing the efficacy of the product compared to placebo
      when applied to reduce pain resulting from treatment of the forehead with CO2 fractional
      laser at 5 mJ fluency and 5% concentration. To assess possible reactions, the photographic
      records were taken prior to the application of both products, as well as immediately prior to
      laser therapy and after 1 hour of laser therapy (1:20 h of application of the products).

      In addition to the efficacy evaluation, the concomitant application of the control product
      (placebo) aimed to verify if possible dermatological reactions would be related to the active
      principle of the product or to the components of the cream base or to the performance of the
      laser therapy. In addition, considering a subgroup of participants, the study allowed the
      assessment of the degree of systemic absorption from the plasma concentrations observed,
      through the collection of blood samples for quantification of the compounds after their
      topical application.

      Phase III, double-blind, monocentric, randomized crossover at the same time (right and left
      sides of forehead) , consisting of 120 patients, phototypes I to III, older than 18 years,
      female or male, with indication of aesthetic treatment with carbon dioxide (CO2) fractional
      laser in the forehead.

      The anesthetic formulation, the object of the study, was administered topically in one side
      of the forehead and the placebo formulation (vehicle of the product) in the opposite side,
      once, as randomized, twenty minutes before the start of the CO2 laser therapy (in both sides
      of the forehead).

      A total of 120 samples (5 g tubes) of the Test formulation and 120 samples (5 g tubes) of the
      Control (placebo) formulation were prepared for the administration of the medication to study
      . Initially, based on identification only on the secondary packaging (labeled plastic bag
      containing only test formulation tubes and labeled plastic bag containing only control
      formulation tubes), the tubes of each formulation were labeled with the subject's subject
      number and the indication of the side ( left or right ) of application, according to
      randomization of the study. After labeling and proper conferencing, these identical looking
      tubes were assembled and sorted by the participant number and left or right , and it was no
      longer possible to distinguish whether a particular tube concerned the test or control
      formulation. This set of samples was forwarded for conducting the study. Those responsible
      for the separation did not participate in the conduct of the study activities.

      The study population consisted of female or male patients, phototypes I to III, with good
      general health conditions and those older than 18 years who had indication of aesthetic
      treatment with CO2 fractional laser compatible with the study proposal . These patients
      attended the clinic either spontaneously.

      The anesthetic formulation and placebo were weighed individually, 2g of each gel, placing
      them directly on a spatula identified as left or right side, on a semi-analytical scale. The
      contents on the spatulas were applied to the corresponding forehead side using the gloved
      finger of the applicator to spread it as evenly as possible, 20 minutes before the session
      with CO2 fractional laser, under the supervision of the clinical investigator. Both test
      product and placebo gel were removed with saline solution and then CO2 laser intensity of 5mJ
      and concentration of 5% was applied across the forehead, always starting the right side
      toward the left side.

      Immediately (0 min) after laser application and at 30, 60 and 90 minutes, it was assessed
      pain sensation in four quadrants of each forehead side using a visual analogue scale. The
      scale consists of a continuous line, whose left end corresponding to the absence of pain ("No
      Pain") and right end corresponding to the worst pain bearable by the patient ("the worst pain
      you can imagine"). The patient scored a perpendicular mark anywhere on the line (including
      the ends) in position to understand better represent the intensity of pain experienced on
      that quadrant at the specific time of each evaluation.

      The evaluations were completed after 90 minutes of laser session (110 minutes after treatment
      with the investigational products) and blood pressure, pulse and temperature measurements
      were performed before the patient was released. At the end of the study, the distance from
      the left end to the mark was measured with a millimeter scale ruler. Two independent persons
      performed this measurement and any discrepancies values were conferred by a third person.

      At the end of the procedure was generated a table in Excel, also conferred with the values
      obtained in centimeters for each occasion, including the total length of the ruler. The value
      in percentage was obtained by dividing the measured value by the total length of the scale by
      100 . The averaged response corresponding to the four quadrants on the left and the average
      of the responses corresponding to the four quadrants on the right was calculated.

      The two values (mean of the left side and mean of the right side) obtained for each of the
      occasions was the value used for the statistical calculation of treatment efficacy. A mean
      reduction of 30% with the topical anesthetic versus placebo - test / placebo ≤0.7 was
      considered clinically significant . The statistical analysis used for efficacy was the paired
      t-test.
    

Intervention name(s): Lidocaine / Prilocaine Cream; placebo
Intervention type(s): Drug; Drug
Intervention description(s): according randomized this side received placebo or active product; according randomized this side received placebo or active product
Intervention MeSH terms: Lidocaine; Prilocaine; Lidocaine, Prilocaine Drug Combination
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Double-blind, crossover study where the same participant received in one side of the forehead the active drug and in the other side of the forehead placebo.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: topical anesthetic; nanocapsules; nanotechnology; lidocaine; prilocaine; fractional CO2 laser resurfacing