Photoallergic Potential of 6% Bemotrizinol
Condition: Photoallergic Response
Study type: Interventional
Phase: Phase 2

Summary: 
      This clinical trial will assess the photoallergic potential of BEMT (6%), compared to a
      vehicle control and a negative control.
    

Detailed description: 
      The primary endpoint of this clinical trial is to evaluate the potential of Bemotrizinol (6%)
      to produce a photoallergic response.

      The potential of 6% Bemotrizinol to produce a photoallergic response after application to the
      skin of human subjects followed by exposure to ultraviolet (UV) radiation will be assessed
      via the evaluation of a sunscreen oil with 6% BEMT and 10% ethanol as penetration enhancer
      (SU E 101413 85), as compared to a sunscreen oil vehicle with 10% ethanol as penetration
      enhancer without BEMT (SU-E-101413-82) and a dispersion of 6% BEMT in petrolatum
      (SU-E-101413-82).

      Upon enrollment, a site on a subject's lower back, isolated from the actual test site, will
      be chosen to determine the subject's Minimal Erythema Dose (MED). The MED of each subject is
      assessed by applying a progressive geometric sequence of UV radiation exposures to five
      sub-sites, each of which is graduated incrementally by 25% over the previous site. The MED is
      evaluated 16 to 24 hours after ultraviolet radiation.

      Duplicate test sites on the back (each approximately 4 cm2) will be identified. Test material
      will be applied to designated patches and affixed to both sides of the back. One side will be
      designated for irradiation, and the other is used as a treated/non-irradiated control.
      Approximately 0.15 g of each investigational product or vehicle controls will be applied to
      the fabric portion of separate patches with occlusive strips; an un-dosed patch will also be
      used.

      Approximately 24 hours after application, the patches will be removed and the skin will be
      gently wiped. The MED will be determined from the five UV-treated sub-sites and all of the
      test sites will be evaluated according to the erythema grading scale. The sites designated
      for irradiation will be then irradiated with solar simulated light by two times an
      individual's MED.

      The remaining site serves as the non-irradiated control. Test sites are delineated with a
      marking pen to ensure continuity of patch application and patch site location.

      There will be three study phases associated with this study: Induction, challenge and
      re-challenge.

      The induction phase procedure will be carried out twice weekly for a total of six
      applications/post-irradiation readings. However, the schedule may be modified to accommodate
      inclement weather, holidays, or missed applications. At the discretion of the Principal
      Investigator, the test material may then be applied, the sites irradiated and scored on two
      consecutive days during the Induction Phase. If a patch and or irradiation is missed, a 3-day
      sequence of patch/irradiation/score will be added at the end of the Induction Phase. Subjects
      must have no fewer than 5 evaluations at the end of the Induction phase. Only one rescheduled
      patch or irradiation procedure is permitted. Subjects missing a second visit are discontinued
      from the study due to non-compliance with the study protocol. For evaluation of photoallergy,
      during the Induction Phase, the sites are irradiated with 2 times the subject's MED (full
      spectrum wavelengths UVB 290-320 nm and UVA 320-400 nm) J/cm2 UVA. During the challenge
      phase, the sites will be irradiated with a dose of 10 J/cm2 of UVA light (320-400 nm) using
      cut-off filters to block UVB wavelength 290-320 nanometers.

      Irradiated area within the treated sites and control sites are examined approximately 24
      hours following irradiation of the test sites and graded. Skin condition of the sites will be
      evaluated at each visit for possible skin reactions to the test material. Any reaction will
      be documented on the source document.

      If a 2+ reaction or greater occurs on a site, the application of the test material may be
      discontinued for the remainder of the Induction Phase, but may be challenged on the
      appropriate day of the study.

      At the discretion of the Principal Investigator, subjects exhibiting a significant reaction
      at the beginning of the Induction Phase may be considered to be "pre-sensitized" to an
      ingredient(s) of the test product and may be discontinued from the patching and irradiation
      of that test material for the remainder of the study.

      The challenge phase will occur approximately 10 to 21 days following the last induction
      application. Duplicate patches are applied to sites previously unexposed to the test
      material. In addition, 2 sets of patches without test material will be also applied on 2
      sides of the back. Approximately 24 hours later, the patches are removed, the test sites are
      evaluated. The test sites on one side of the back are irradiated with a non-erythrogenic dose
      of Ultra Violet A (UVA) radiation (wavelengths 320-400 nm) equivalent to approximately 10
      J/cm². The sites on the other side of the back serve as a "test material treated,
      non-irradiated" control site and "non-treated, non-irradiated" control. The challenge sites
      are graded at 24, 48, and 72 hours following irradiation according to the dermal grading
      scale.

      A re-challenge phase may be initiated at the discretion of the Investigator, and with the
      Sponsor's approval. A subject may be re-challenged with the test material if reactions
      indicative of sensitization or photo sensitization are observed during the Challenge Phase.
      The subject(s) will be asked to return to the laboratory no sooner than two weeks following
      the conclusion of the PA study and the Challenge procedures will be repeated. One patch of
      the test material will be applied to the subject's back and allowed to remain in direct
      contact with the skin for 24 hours. The subject will return after 24 hours for removal of the
      patch and grading of the site, without irradiation if sensitization is suspected or with
      irradiation of an additional treated site (24 hour exposure) if reactions suggestive of
      photosensitization are observed during the study. Subjects will return for a 48 hour and 72
      hour post-patch application grading and additional 96 hour evaluation if a reaction persists.
      If the sites are irradiated after patch removal, subjects will return for evaluation at 24
      hour, 48 hour and 72 hour post UV exposure.
    

Intervention name(s): 6% Bemotrizinol in sunscreen formulation; 6% Bemotrizinol in petrolatum; Vehicle
Intervention type(s): Drug; Drug; Other
Intervention description(s): 6% Bemotrizinol (BEMT) in a basic sunscreen oil formulation (SU E 101413 85); 6% Bemotrizinol (BEMT) as a dispersion in petrolatum (SU-E-101413-82); Sunscreen oil vehicle with 10% ethanol as penetration enhancer without BEMT (SU E 101413 91)
Other intervention name(s): PARSOL SHIELD; PARSOL SHIELD
Intervention MeSH terms: Sunscreening Agents; Petrolatum
Allocation: Non-Randomized
Intervention model: Factorial Assignment
Intervention model description: This study will evaluate the potential of an investigational product (6% Bemotrizinol (BEMT) in a suitable vehicle (i.e., sunscreen oil SU E 101413 85) or petrolatum (SU-E-101413-82)) to produce a photoallergic response after application to the skin of human subjects followed by exposure to UV radiation.
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Sunscreen, photoprotective, UV-filter