Assessment of the Human Systemic Absorption of Sunscreen Ingredients

Phase 1

Completed

Conditions: Systemic Exposure to Sunscreen Ingredients

Registration Number: NCT03582215

Lead Sponsor: Food and Drug Administration (FDA)

Brief 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 72

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Avobenzone Maximum Concentration	0, 0.5, 1, 1.5, 2, 4, 6, 8, 9, 10, 12, 14, 23, 28, 33, 47, 52, 57, 71, 73, 74, 76, 78, 81, 82, 84, 86, 95, 120, and 144 h for Part 1; same time points and 216, 312, and 480 h for Part 2	Maximum concentration (observed peak drug concentration) (Cmax)

Secondary Outcome Measures

Name	Time	Method
Oxybenzone Maximum Concentration	0, 0.5, 1, 1.5, 2, 4, 6, 8, 9, 10, 12, 14, 23, 28, 33, 47, 52, 57, 71, 73, 74, 76, 78, 81, 82, 84, 86, 95, 120, and 144 h for Part 1; same time points and 216, 312, and 480 h for Part 2	Maximum concentration (observed peak drug concentration) (Cmax)
Octinoxate Maximum Concentration	0, 0.5, 1, 1.5, 2, 4, 6, 8, 9, 10, 12, 14, 23, 28, 33, 47, 52, 57, 71, 73, 74, 76, 78, 81, 82, 84, 86, 95, 120, 144, 216, 312, and 480 h for Part 2	Maximum concentration (observed peak drug concentration) (Cmax)
Octocrylene Maximum Concentration	0, 0.5, 1, 1.5, 2, 4, 6, 8, 9, 10, 12, 14, 23, 28, 33, 47, 52, 57, 71, 73, 74, 76, 78, 81, 82, 84, 86, 95, 120, and 144 h for Part 1; same time points and 216, 312, and 480 h for Part 2	Maximum concentration (observed peak drug concentration) (Cmax)
Ecamsule Maximum Concentration	0, 0.5, 1, 1.5, 2, 4, 6, 8, 9, 10, 12, 14, 23, 28, 33, 47, 52, 57, 71, 73, 74, 76, 78, 81, 82, 84, 86, 95, 120, and 144 h for Part 1	Maximum concentration (observed peak drug concentration) (Cmax)
Homosalate Maximum Concentration	0, 0.5, 1, 1.5, 2, 4, 6, 8, 9, 10, 12, 14, 23, 28, 33, 47, 52, 57, 71, 73, 74, 76, 78, 81, 82, 84, 86, 95, 120, 144, 216, 312, and 480 h for Part 2	Maximum concentration (observed peak drug concentration) (Cmax)
Octisalate Maximum Concentration	0, 0.5, 1, 1.5, 2, 4, 6, 8, 9, 10, 12, 14, 23, 28, 33, 47, 52, 57, 71, 73, 74, 76, 78, 81, 82, 84, 86, 95, 120, 144, 216, 312, and 480 h for Part 2	Maximum concentration (observed peak drug concentration) (Cmax)