Assessment of the Human Systemic Absorption of Sunscreen Ingredients

NCT03582215 | Completed Phase 1 Results FDA Drug

• 1 other identifier: SCR-005
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

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).

Conditions

Systemic Exposure to Sunscreen Ingredients

Keywords

Sunscreen; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Avobenzone Maximum Concentration

  Maximum concentration (observed peak drug concentration) (Cmax)

  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

Secondary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

Study Arms (8)

Part 1: Cream

EXPERIMENTAL

Part 1: Cream Ingredients: 2% Avobenzone; 10% Octocrylene; 2% Ecamsule

Drug: Part 1: Cream

Part 1: Lotion

EXPERIMENTAL

Part 1: Lotion Ingredients: 3% Avobenzone; 4% Oxybenzone; 6% Octocrylene

Drug: Part 1: Lotion

Part 1: Spray 1

EXPERIMENTAL

Part 1: Spray 1 Ingredients: 3% Avobenzone; 6% Oxybenzone; 2.35% Octocrylene; 15% Homosalate; 5% Octisalate

Drug: Part 1: Spray 1

Part 1: Spray 2

EXPERIMENTAL

Part 1: Spray 2 Ingredients: 3% Avobenzone; 5% Oxybenzone; 10% Octocrylene

Drug: Part 1: Spray 2

Part 2: Lotion

EXPERIMENTAL

Part 2: Lotion Ingredients: 3% Avobenzone; 4% Oxybenzone; 6% Octocrylene

Drug: Part 2: Lotion

Part 2: Aerosol Spray

EXPERIMENTAL

Part 2: Aerosol Spray Ingredients: 3% Avobenzone; 6% Oxybenzone; 10% Octocrylene; 15% Homosalate; 5% Octisalate

Drug: Part 2: Aerosol Spray

Part 2: Nonaerosol Spray

EXPERIMENTAL

Part 2: Nonaerosol Spray Ingredients: 3% Avobenzone; 10% Octocrylene; 10% Homosalate; 5% Octisalate; 7.5% Octinoxate

Drug: Part 2: Nonaerosol Spray

Part 2: Pump Spray

EXPERIMENTAL

Part 2: Pump Spray Ingredients: 3% Avobenzone; 10% Homosalate; 5% Octisalate; 7.5% Octinoxate

Drug: Part 2: Pump Spray

Interventions

Part 1: Cream DRUG

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

Also known as: Avobenzone, Octocrylene, Ecamsule

Part 1: Cream

Part 1: Lotion DRUG

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

Also known as: Avobenzone, Oxybenzone, Octocrylene

Part 1: Lotion

Part 1: Spray 1 DRUG

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

Also known as: Avobenzone, Homosalate, Octisalate, Octocrylene, Oxybenzone

Part 1: Spray 1

Part 1: Spray 2 DRUG

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

Also known as: Avobenzone, Oxybenzone, Octocrylene

Part 1: Spray 2

Part 2: Lotion DRUG

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

Also known as: Avobenzone, Oxybenzone, Octocrylene

Part 2: Lotion

Part 2: Aerosol Spray DRUG

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

Also known as: Avobenzone, Oxybenzone, Octocrylene, Homosalate, Octisalate

Part 2: Aerosol Spray

Part 2: Nonaerosol Spray DRUG

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

Also known as: Avobenzone, Octocrylene, Homosalate, Octisalate, Octinoxate

Part 2: Nonaerosol Spray

Part 2: Pump Spray DRUG

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

Also known as: Avobenzone, Homosalate, Octisalate, Octinoxate

Part 2: Pump Spray

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject signs an institutional review board (IRB) approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act authorization) before any study related procedures are performed.
• Subject is a healthy man or woman, 18 to 60 years of age, inclusive, who has a body mass index of 18.5 to 29.9 kg/m2, inclusive, at Screening.
• Subject has normal medical history findings, clinical laboratory results, vital sign measurements, 12 lead electrocardiogram (ECG) results, and physical examination findings at Screening or, if abnormal, the abnormality is not considered clinically significant (as determined and documented by the investigator or designee).
• Subject must have a negative test result for alcohol and drugs of abuse at screening and Check-in (Day 0).
• Subject has no known or suspected allergies or sensitivities to any components of the sunscreen formulation.
• Female subjects must be of non-childbearing potential or, if they are of childbearing potential, they must: 1) have been strictly abstinent for 1 month before Check in (Day 0) and agree to remain strictly abstinent for the duration of the study and for at least 1 month after the last application of study drug; OR 2) be practicing 2 highly effective methods of birth control (as determined by the investigator or designee; one of the methods must be a barrier technique) from at least 1 month before Check in (Day 0) until at least 1 month after the last application of study drug.
• Female subjects must not be pregnant or lactating before enrollment in the study.
• Male subjects must agree to practice 2 highly effective methods of birth control (as determined by the investigator or designee; one of the methods must be a barrier technique) from at least 1 month before Check in (Day 0) until at least 1 month after the last application of study drug.
• Subject is highly likely (as determined by the investigator) to comply with the protocol defined procedures and to complete the study.
• Note: subjects with any skin type or skin pigment type may be eligible for the study.

You may not qualify if:

• Subject has broken, irritated, or unhealed skin.
• Subject has an active sunburn.
• Subject has used a tanning bed in the previous 4 weeks.
• Subject has known skin or autoimmune disease(s).
• Subject is anemic or has any chronic condition(s) that may impact blood sample collection.
• Subject has any underlying disease or surgical or medical condition (e.g., cancer, human immunodeficiency virus \[HIV\], severe hepatic or renal impairment) that could put the subject at risk or would normally prevent participation in a clinical study.
• Subject has known or suspected allergies or sensitivities to any components of the sunscreen formulation.
• Subject has clinical laboratory test results (hematology and serum chemistry) at Screening that are outside the reference ranges provided by the clinical laboratory and considered clinically significant by the investigator.
• Subject has a positive test result at Screening for HIV 1 or 2 antibody, hepatitis C virus antibodies, or hepatitis B surface antigen.
• Subject is unable or unwilling to undergo multiple venipunctures for blood sample collection because of poor tolerability or poor venous access.
• Subject has received or applied the topical sunscreen formulations used in the current study, or any other product containing the active ingredients of the topical sunscreen formulations used in the current study, within 7 days before Check in (Day 0).
• Subject has used any personal care product(s) containing any active sunscreen ingredient, such sunscreen products, hand or body moisturizing lotion, makeup or foundation, lip balm, or lipstick, within 7 days before Check in (Day 0).
• Subject is unable or unwilling to tolerate the scent of sunscreen for the duration of the treatment period.

Sponsors & Collaborators

• Food and Drug Administration (FDA): lead
• Spaulding Clinical Research LLC: collaborator

Study Sites (1)

Spaulding Clinical Research

West Bend, Wisconsin, 53095, United States

Location

Related Publications (3)

• Matta MK, Zusterzeel R, Pilli NR, Patel V, Volpe DA, Florian J, Oh L, Bashaw E, Zineh I, Sanabria C, Kemp S, Godfrey A, Adah S, Coelho S, Wang J, Furlong LA, Ganley C, Michele T, Strauss DG. Effect of Sunscreen Application Under Maximal Use Conditions on Plasma Concentration of Sunscreen Active Ingredients: A Randomized Clinical Trial. JAMA. 2019 Jun 4;321(21):2082-2091. doi: 10.1001/jama.2019.5586.

  PMID: 31058986 RESULT

• Matta MK, Florian J, Zusterzeel R, Pilli NR, Patel V, Volpe DA, Yang Y, Oh L, Bashaw E, Zineh I, Sanabria C, Kemp S, Godfrey A, Adah S, Coelho S, Wang J, Furlong LA, Ganley C, Michele T, Strauss DG. Effect of Sunscreen Application on Plasma Concentration of Sunscreen Active Ingredients: A Randomized Clinical Trial. JAMA. 2020 Jan 21;323(3):256-267. doi: 10.1001/jama.2019.20747.

  PMID: 31961417 RESULT

• Najjar A, Schepky A, Krueger CT, Dent M, Cable S, Li H, Gregoire S, Roussel L, Noel-Voisin A, Hewitt NJ, Cardamone E. Use of Physiologically-Based Kinetics Modelling to Reliably Predict Internal Concentrations of the UV Filter, Homosalate, After Repeated Oral and Topical Application. Front Pharmacol. 2022 Jan 4;12:802514. doi: 10.3389/fphar.2021.802514. eCollection 2021.

  PMID: 35058784 DERIVED

MeSH Terms

Interventions

avobenzone; octocrylene; terephthalylidene dicamphor sulfonic acid; oxybenzone; homosalate; 2-ethylhexyl salicylate; octylmethoxycinnamate

Limitations and Caveats

The study was conducted in indoor conditions and was not designed to assess differences by formulation or participant factors.

Results Point of Contact

• Title: David Strauss, MD, PhD
• Organization: U.S. Food and Drug Administration

David.strauss@fda.hhs.gov

301-796-6323

Study Officials

• Carlos R Sanabria, MD

  Spaulding Clinical Research LLC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 27, 2018
• First Posted: July 10, 2018
• Study Start: July 18, 2018
• Primary Completion: February 18, 2019
• Study Completion: February 18, 2019
• Last Updated: April 21, 2020
• Results First Posted: April 21, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Jan 2020 - supplementary materials included with publications
• Access Criteria: Access to JAMA. De-identified data has been included under supplement 3 for Part 1 (Matta et al, 2019 JAMA) and Part 2 (Matta et al, 2020, JAMA) of this clinical study Part 1 study data: https://cdn.jamanetwork.com/ama/content\ public/journal/jama/938034/jpc190002supp3\ prod.xlsx

Locations

US (1)