Assessment of the Human Systemic Absorption of Sunscreen Ingredients
Condition: Systemic Exposure to Sunscreen Ingredients
Study type: Interventional
Phase: Phase 1

Summary: 
      This study is designed to assess the systemic exposure and pharmacokinetics of sunscreen
      active ingredients (avobenzone, oxybenzone, ecamsule, octocrylene homosalate, octisalate and
      octinoxate) when sunscreen product is applied under maximal use conditions.

      Part 1 is an open-label, randomized, 4-arm study in 24 healthy adult subjects with the
      primary objective to explore whether the active components (avobenzone, oxybenzone, ecamsule
      and octocrylene) of 4 sunscreen products (1 sunscreen product in each arm) are absorbed into
      the systemic circulation when a sunscreen product is applied under maximal use conditions.

      One sunscreen product with the highest avobenzone exposure will be selected for the second
      part of the study. If there is no quantifiable exposure of avobenzone for any of the
      sunscreen products, the formulation with the highest oxybenzone exposure will be selected for
      Part 2. In addition, 3 new sunscreen products are included in Part 2.

      Part 2 is an open label, 4-arm study in 48 healthy adult subjects with the primary objective
      to assess the pharmacokinetics of the active components in the selected product from Part 1
      and 3 additional products with a combination of active ingredients (avobenzone, oxybenzone,
      octocrylene, ecamsule homosalate, octisalate and octinoxate as applicable/contained in the
      different products).
    

Detailed description: 
      Part 1

      Part 1 is an open label, randomized, 4-arm pilot study to evaluate the effects of multiple
      applications of 4 different topical sunscreen formulations in healthy adult subjects. Each
      arm will include 6 subjects (3 male and 3 female) with 1 formulation. A total of 24 subjects
      (12 male and 12 female) from all 4 arms will be admitted to the clinical research unit (CRU)
      on Day 0. On the morning of Days 1 through 4, subjects will receive a topical application of
      the study drug at approximately 0900 hours. The study product will be weighed in advance and
      applied by a qualified person from the study team. Subjects will then receive 3 more topical
      applications on the same day at 2, 4, and 6 hours after the first dose.

      Part 2

      Part 2 is an open label, 4-arm study to evaluate the pharmacokinetics of avobenzone,
      oxybenzone, octocrylene, ecamsule homosalate, octisalate and octinoxate (as applicable in the
      different products) after multiple applications of a topical sunscreen formulation in healthy
      adult subjects. Part 2 will include 48 subjects (24 male and 24 female) and each arm will
      include 12 subjects (6 male and 6 female). One of the formulations in Part 2 will be selected
      based on the plasma exposure data from the pilot study (Part 1). A total of 48 subjects (24
      male and 24 female) will be admitted to the CRU on Day 0. On the morning of Days 1 through 4,
      subjects will receive a topical application of the study product at approximately 0900 hours.
      The study drug will be weighed in advance and applied by a qualified person from the study
      team. Subjects will only receive one application on Day 1. On Days 2, 3 and 4 subjects will
      receive an initial dose and 3 more topical applications on the same day at 2, 4, and 6 hours
      after the first dose.

      Parts 1 and 2

      In both parts, approximately 2 mg of active sunscreen ingredient per 1 cm2 of body surface
      (calculation per method of Dubois) will be evenly applied 4 times per study day (except for a
      one-time application on the first day in part 2) to areas of the body typically exposed to
      the sun: face, ears, neck, torso, arms, and legs (approximately 75% of the body surface
      area). The antecubital areas will be avoided when applying the sunscreen due to potential
      contamination of the sites used for intravenous pharmacokinetic (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 dose of the day), but not at other times during the day.

      Blood samples (approximately 10 mL per sample) will be collected for determination of plasma
      concentrations for all active ingredients (avobenzone, oxybenzone, octocrylene, ecamsule,
      homosalate, octisalate and octinoxate, where applicable).

      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
      clinical research unit (CRU) staff will be recorded. Any AE reported after the informed
      consent is signed and before study drug application will be recorded as medical history.

      Subjects will remain in the CRU after admission on Day 0 until the morning of Day 7 following
      completion of scheduled end-of-study activities for Part 1. For Part 2, subjects will undergo
      the same schedule but will return to the clinic for follow-up visits on Days 10, 14 and 21.
      Subjects will then be discharged following completion of End-of-Study activities.

      Subjects are not allowed to use products containing any of these active ingredients from 7
      days before check-in until completion of End-of-Study procedures.
    

Intervention name(s): Part 1: Cream; Part 1: Lotion; Part 1: Spray 1; Part 1: Spray 2; Part 2: Lotion; Part 2: Aerosol Spray; Part 2: Nonaerosol Spray; Part 2: Pump Spray
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Approximately 2 mg per cm2 of body surface will be applied topically 4 times per day for 4 days to approximately 75% of the body surface area; Approximately 2 mg per cm2 of body surface will be applied topically 4 times per day for 4 days to approximately 75% of the body surface area; Approximately 2 mg per cm2 of body surface will be applied topically 4 times per day for 4 days to approximately 75% of the body surface area; Approximately 2 mg per cm2 of body surface will be applied topically 4 times per day for 4 days to approximately 75% of the body surface area; Approximately 2 mg per cm2 of body surface will be applied topically 1 time on day 1 and 4 times per day on following 3 days to approximately 75% of the body surface area; Approximately 2 mg per cm2 of body surface will be applied topically 1 time on day 1 and 4 times per day on following 3 days to approximately 75% of the body surface area; Approximately 2 mg per cm2 of body surface will be applied topically 1 time on day 1 and 4 times per day on following 3 days to approximately 75% of the body surface area; Approximately 2 mg per cm2 of body surface will be applied topically 1 time on day 1 and 4 times per day on following 3 days to approximately 75% of the body surface area
Other intervention name(s): Avobenzone; Octocrylene; Ecamsule; Avobenzone; Oxybenzone; Octocrylene; Avobenzone; Homosalate; Octisalate; Octocrylene; Oxybenzone; Avobenzone; Oxybenzone; Octocrylene; Avobenzone; Oxybenzone; Octocrylene; Avobenzone; Oxybenzone; Octocrylene; Homosalate; Octisalate; Avobenzone; Octocrylene; Homosalate; Octisalate; Octinoxate; Avobenzone; Homosalate; Octisalate; Octinoxate
Intervention MeSH terms: Salicylates; Avobenzone; Oxybenzone; Homosalate; 2-ethylhexyl salicylate; Octylmethoxycinnamate
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Part 1 of the study has 4 parallel arms where 4 different sunscreen products will be studied. Part 2 of the study has 4 parallel arms where 4 sunscreen products (one from Part 1 and 3 new sunscreen products) will be studied.
Masking: None (Open Label)
Primary purpose: Other
Keywords: Sunscreen; Pharmacokinetics