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Assessment of the Human Systemic Absorption of Sunscreen Ingredients

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ClinicalTrials.gov Identifier: NCT03582215
Recruitment Status : Completed
First Posted : July 10, 2018
Last Update Posted : November 7, 2019
Sponsor:
Collaborator:
Spaulding Clinical Research LLC
Information provided by (Responsible Party):
Food and Drug Administration (FDA)

Tracking Information
First Submitted Date  ICMJE June 27, 2018
First Posted Date  ICMJE July 10, 2018
Last Update Posted Date November 7, 2019
Actual Study Start Date  ICMJE July 18, 2018
Actual Primary Completion Date February 18, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 6, 2018)
Avobenzone maximum concentration [ Time Frame: 7 days for Part 1; 21 days for Part 2 ]
Maximum concentration (observed peak drug concentration) (Cmax)
Original Primary Outcome Measures  ICMJE
 (submitted: June 27, 2018)
Avobenzone maximum concentration [ Time Frame: 7 days ]
Maximum concentration (observed peak drug concentration) (Cmax)
Change History Complete list of historical versions of study NCT03582215 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 6, 2018)
  • Oxybenzone maximum concentration [ Time Frame: 7 days for Part 1; 21 days for Part 2 ]
    Maximum concentration (observed peak drug concentration) (Cmax)
  • Octocrylene maximum concentration [ Time Frame: 7 days for Part 1; 21 days for Part 2 ]
    Maximum concentration (observed peak drug concentration) (Cmax)
  • Ecamsule maximum concentration [ Time Frame: 7 days for Part 1; 21 days for Part 2 ]
    Maximum concentration (observed peak drug concentration) (Cmax)
  • Homosalate maximum concentration [ Time Frame: 7 days for Part 1; 21 days for Part 2 ]
    Maximum concentration (observed peak drug concentration) (Cmax)
  • Octisalate maximum concentration [ Time Frame: 7 days for Part 1; 21 days for Part 2 ]
    Maximum concentration (observed peak drug concentration) (Cmax)
  • Octinoxate maximum concentration [ Time Frame: 7 days for Part 1; 21 days for Part 2 ]
    Maximum concentration (observed peak drug concentration) (Cmax)
Original Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2018)
  • Oxybenzone maximum concentration [ Time Frame: 7 days ]
    Maximum concentration (observed peak drug concentration) (Cmax)
  • Octocrylene maximum concentration [ Time Frame: 7 days ]
    Maximum concentration (observed peak drug concentration) (Cmax)
  • Ecamsule maximum concentration [ Time Frame: 7 days ]
    Maximum concentration (observed peak drug concentration) (Cmax)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Assessment of the Human Systemic Absorption of Sunscreen Ingredients
Official Title  ICMJE Assessment of the Human Systemic Absorption of Sunscreen Ingredients
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE 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
Condition  ICMJE Systemic Exposure to Sunscreen Ingredients
Intervention  ICMJE
  • Drug: Part 1: Sunscreen Product #1 (Cream)
    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
    Other Names:
    • Avobenzone
    • Octocrylene
    • Ecamsule
  • Drug: Part 1: Sunscreen Product #2 (Lotion)
    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
    Other Names:
    • Avobenzone
    • Oxybenzone
    • Octocrylene
  • Drug: Part 1: Sunscreen Product #3 (Spray)
    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
    Other Names:
    • Avobenzone
    • Homosalate
    • Octisalate
    • Octocrylene
    • Oxybenzone
  • Drug: Part 1: Sunscreen Product #4 (Spray)
    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
    Other Names:
    • Avobenzone
    • Oxybenzone
    • Octocrylene
  • Drug: Part 2: Sunscreen Product #1, 2, 3 or 4
    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 Names:
    • Avobenzone
    • Oxybenzone
    • Octocrylene
    • Homosalate
    • Octisalate
    • Ecamsule
  • Drug: Part 2: Sunscreen Product #5 (Spray)
    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 Names:
    • Avobenzone
    • Oxybenzone
    • Octocrylene
    • Homosalate
    • Octisalate
  • Drug: Part 2: Sunscreen Product #6 (Spray)
    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 Names:
    • Avobenzone
    • Octocrylene
    • Homosalate
    • Octisalate
    • Octinoxate
  • Drug: Part 2: Sunscreen Product #7 (Spray)
    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 Names:
    • Avobenzone
    • Homosalate
    • Octisalate
    • Octinoxate
Study Arms  ICMJE
  • Experimental: Part 1: Product #1
    Part 1: Sunscreen Product #1 (Cream)
    Intervention: Drug: Part 1: Sunscreen Product #1 (Cream)
  • Experimental: Part 1: Product #2
    Part 1: Sunscreen Product #2 (Lotion)
    Intervention: Drug: Part 1: Sunscreen Product #2 (Lotion)
  • Experimental: Part 1: Product #3
    Part 1: Sunscreen Product #3 (Spray)
    Intervention: Drug: Part 1: Sunscreen Product #3 (Spray)
  • Experimental: Part 1: Product #4
    Part 1: Sunscreen Product #4 (Spray)
    Intervention: Drug: Part 1: Sunscreen Product #4 (Spray)
  • Experimental: Part 2: Product #1, 2, 3 or 4

    Part 2: Sunscreen Product #1, 2, 3 or 4.

    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.

    Intervention: Drug: Part 2: Sunscreen Product #1, 2, 3 or 4
  • Experimental: Part 2: Product #5
    Part 2: Sunscreen Product #5 (Spray)
    Intervention: Drug: Part 2: Sunscreen Product #5 (Spray)
  • Experimental: Part 2: Product #6
    Part 2: Sunscreen Product #6 (Spray)
    Intervention: Drug: Part 2: Sunscreen Product #6 (Spray)
  • Experimental: Part 2: Product #7
    Part 2: Sunscreen Product #7 (Spray)
    Intervention: Drug: Part 2: Sunscreen Product #7 (Spray)
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 6, 2018)
72
Original Estimated Enrollment  ICMJE
 (submitted: June 27, 2018)
48
Actual Study Completion Date  ICMJE February 18, 2019
Actual Primary Completion Date February 18, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Subjects who meet all of the following inclusion criteria will be eligible to participate in the study:

  1. 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.
  2. 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.
  3. 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).
  4. Subject must have a negative test result for alcohol and drugs of abuse at screening and Check-in (Day 0).
  5. Subject has no known or suspected allergies or sensitivities to any components of the sunscreen formulation.
  6. 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.
  7. Female subjects must not be pregnant or lactating before enrollment in the study.
  8. 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.
  9. 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.

Subjects who meet any of the following exclusion criteria will not be eligible to participate in the study:

  1. Subject has broken, irritated, or unhealed skin.
  2. Subject has an active sunburn.
  3. Subject has used a tanning bed in the previous 4 weeks.
  4. Subject has known skin or autoimmune disease(s).
  5. Subject is anemic or has any chronic condition(s) that may impact blood sample collection.
  6. 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.
  7. Subject has known or suspected allergies or sensitivities to any components of the sunscreen formulation.
  8. 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.
  9. Subject has a positive test result at Screening for HIV 1 or 2 antibody, hepatitis C virus antibodies, or hepatitis B surface antigen.
  10. Subject is unable or unwilling to undergo multiple venipunctures for blood sample collection because of poor tolerability or poor venous access.
  11. 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).
  12. 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).
  13. Subject is unable or unwilling to tolerate the scent of sunscreen for the duration of the treatment period.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03582215
Other Study ID Numbers  ICMJE SCR-005
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Food and Drug Administration (FDA)
Study Sponsor  ICMJE Food and Drug Administration (FDA)
Collaborators  ICMJE Spaulding Clinical Research LLC
Investigators  ICMJE
Principal Investigator: Carlos R Sanabria, MD Spaulding Clinical Research LLC
PRS Account Food and Drug Administration (FDA)
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP