Bemotrizinol UV Filter Part 1 Clinical PK Evaluation in Topical MUsT Study
Condition: Absorption; Chemicals; Sunscreening Agents
Study type: Interventional
Phase: Phase 1

Summary: 
      This will be a single clinical study conducted in 2 parts (Part 1: pilot study and Part 2:
      pivotal study).

      Part 1 is an open-label, 1-arm study in 14 healthy adult subjects with the following primary
      objectives:

        -  Primary: To explore whether the active component, bemotrizinol (BEMT), is absorbed from
           a high-penetrating sunscreen formulation including 6% BEMT into the systemic circulation
           when applied under maximal-use conditions.

        -  Secondary: To obtain information needed for a successful pivotal study such as
           preliminary pharmacokinetic (PK) data, validation of study and analytical procedures,
           and the number of subjects needed.

      Part 2 is an open-label, randomized, 3-arm study in 42 healthy adult subjects with the
      following objective:

      • Primary: To assess the systemic absorption and pharmacokinetics of BEMT from 3 market image
      sunscreen formulations under maximal-use conditions.
    

Detailed description: 
      This will be a single clinical study conducted in 2 parts (Part 1: pilot study and Part 2:
      pivotal study). The duration of study participation will be approximately 42 days for Part 1,
      including a 30-day screening period, a 4-day treatment period (Days 1-4), and subjects
      leaving the clinical research unit (CRU) on the morning of Day 5. Subjects will then return
      to the CRU for follow-up visits on Days 8 and 12. On Day 12, End-of-Study activities will be
      completed. For Part 2, the duration of participation will be approximately the same, 42 days,
      and may be adjusted based on the results of Part 1.

      Part 1 is an open-label, 1-arm pilot study to evaluate the effects of multiple applications
      of a topical sunscreen formulation in healthy adult subjects. It will include 14 subjects (7
      male and 7 female) that will be admitted to the CRU on Day -1.

      On the morning of Days 1 through 4, subjects will receive a topical application of the study
      drug between 07:00 and 10:00 hours followed by 3 more applications each day at 2, 4, and 6
      hours after the first application, resulting in study drug application at 0, 2, 4, 6, 24, 26,
      28, 30, 48, 50, 52, 54, 72, 74, 76, and 78 hours relative to the first application. The
      weight of study drug will be measured and recorded before and after dosing for each subject
      and each dose will be applied by a qualified person from the CRU.

      Blood samples will be collected for the determination of plasma concentrations of BEMT from
      before the first topical application of study drug to 264 hours after the first study drug
      application.

      Part 2 is an open-label, randomized, 3-arm pivotal study to evaluate the pharmacokinetics of
      BEMT after multiple applications of a topical sunscreen formulation in healthy adult subjects
      and may be modified based on observations from Part 1 and the Food and Drug Administration
      (FDA) revision. Part 2 will include 14 subjects (7 male and 7 female) in each arm. At least 3
      formulations will be selected based on the plasma exposure data from the pilot study (Part
      1), the in vitro permeation testing (IVPT) results, and the market survey for BEMT-containing
      formulations. All 42 subjects will be admitted to the CRU on Day -1 and randomly assigned to
      a treatment arm before study drug application on Day 1.

      On the morning of Day 1, the assigned study drug will be applied topically between 07:00 and
      10:00 hours; on Days 2, 3, and 4, subjects will receive an initial application at the same
      time as on Day 1 and 3 more topical applications at 2, 4, and 6 hours after the first
      application, resulting in study drug application at 0, 24, 26, 28, 30, 48, 50, 52, 54, 72,
      74, 76, and 78 hours relative to the first application. The weight of study drug will be
      measured and recorded both before and after dosing for each subject and each dose will be
      applied by a qualified person from the CRU.

      The PK blood sample collection schedule for Part 2 will be based on the results from Part 1.
      If significant systemic exposure is observed in Part 1, additional PK blood samples may be
      collected in Part 2 for assessment of metabolites.

      In both parts of the study, In Parts 1 and 2, approximately 2 mg of active sunscreen
      ingredient per 1 cm2 of body surface area (calculation per method of Du Bois and Du Bois
      [1989]) will be evenly applied 4 times per study day (except for a 1-time application on the
      first day in Part 2) to areas of the body typically exposed to the sun: face (except eye
      area), ears, neck, torso, arms, and legs (at least 75% of the body surface area). The
      antecubital areas will be avoided and protected with an occlusive, self-adhesive cover when
      applying the sunscreen due to potential contamination of the sites used for PK blood sample
      collection. The topical applications of study drug will be administered with subjects in swim
      wear to simulate real world settings as well as for easy application. In addition to swim
      wear, subjects may wear scrubs in between applications and at other times throughout the
      day/night. Subjects are required to shower each morning after the first PK blood sample
      collection (and before the first application of the day), but not at other times during the
      day.

      Safety evaluations will include adverse event (AE) monitoring, vital sign measurements, and
      physical examinations. All AEs reported by the subject or observed by the investigator or CRU
      staff will be recorded. Any AE reported after the informed consent form is signed and before
      study drug application will be recorded as medical history.

      In the context of the Coronavirus (COVID-19) pandemic, the clinical site will follow all FDA,
      Centers for Disease Control and Prevention (CDC), and institutional review board (IRB)
      recommendations in its oversight and conduct of the trial. This may include changing the
      schedule of follow-up visits if it is considered necessary after a full risk/benefit
      analysis.
    

Intervention name(s): Bemotrizinol
Intervention type(s): Drug
Intervention description(s): Market-image topical sunscreen formulation containing BEMT (6%)
Other intervention name(s): Bis-ethylhexyloxyphenol Methoxyphenyl Triazine, BEMT, PARSOL Shield, Tinosorb S, UNII-PWZ1720CBH, CAS: 187393-00-6
Intervention model: Single Group Assignment
Intervention model description: Part 1 is an open label, 1-arm pilot study to evaluate the effects of multiple applications of a topical sunscreen formulation in healthy adult subjects.
Masking: None (Open Label)
Primary purpose: Basic Science