Clobetasol Topical Oil for Children With Moderate to Severe Atopic Dermatitis

Open-Label Study of the Pharmacokinetics and Safety Including HPA Axis Suppression Potential of Clobetasol Topical Oil in Pediatric Subjects With Moderate to Severe Atopic Dermatitis

Open-Label Study designed to evaluate the HPA axis suppression potential of Clobetasol Topical Oil and pharmacokinetic safety / systemic exposure to clobetasol when Clobetasol Topical Oil is applied to pediatric subjects with moderate to severe atopic dermatitis (AD) under maximal use conditions.

The study duration for each subject will be up to 54 days (up to 38 days for Screening assessments, followed by up to 16 days of treatment and follow-up). Additional time will be required for subjects requiring additional hypothalamic-pituitary-adrenal [HPA] axis function testing due to an abnormal result at End of Treatment.

Study Overview

• Status: Terminated
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Clobetasol propionate 0.05% Topical Oil

Detailed Description

This study is a multicenter, open-label study designed to evaluate the HPA axis suppression potential and systemic exposure to clobetasol, when administered as Clobetasol Topical Oil in pediatric subjects, under conditions consistent with anticipated clinical use and under conditions designed to maximize the potential for drug absorption in subjects with moderate to severe AD. The study will consist of three successively younger pediatric cohorts, as safety data allow:

• Cohort 1: ≥12 to <18 years;
• Cohort 2: ≥6 to <12 years; and
• Cohort 3: ≥2 to <6 years. Enrollment into each successively younger pediatric cohort will proceed only after the preceding cohort has been completed and safety and exploratory data (including adverse events [AEs], tolerability assessments, clinical laboratory results, and the percentage of subjects with HPA axis suppression) have been reviewed and agreed to be acceptable for progression to the next cohort. Enrollment into Cohorts 2 and 3 will proceed only if the percentage of subjects with HPA axis suppression in Cohorts 1 and 2, respectively, is ≤40%. HPA axis suppression is defined as a cortisol concentration ≤18 µg/100 mL at approximately 30 minutes after stimulation with cosyntropin.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Sanford, Florida, United States, 32771
      • International Clinical Research - US, LLC
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Aeroallergy Research Laboratories of Savannah, Inc
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Paddington Testing Co., Inc.
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research
  • Texas
    • San Antonio, Texas, United States, 78213
      • Progressive Clinical Research
  • Virginia
    • Richmond, Virginia, United States, 23220
      • Clinical Research Partners, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects in good general health confirmed by medical history.
• Subjects with a clinical diagnosis of AD (according to the criteria of Hanifin and Rajka) of moderate to severe intensity (ISGA score of 3 or 4) involving ≥25% to ≤50% of total BSA located within treatable areas (Cohort 1), or ≥35% to ≤50% of total BSA located within treatable areas (Cohorts 2 and 3), with treatable areas including all but the face, axillae, groin, and scalp.
• Subjects with a normally functioning HPA axis, defined as a prestimulation serum cortisol level >5 µg/100 mL, and a response to cosyntropin stimulation to >18 µg/100 mL (after approximately 30 minutes); both blood draws for this test should be performed in the morning, if possible
• Female subjects of childbearing potential must have a negative urine pregnancy test, must not be breastfeeding, and must agree to use an acceptable form of birth control for the duration of the study. Female subjects of childbearing potential are defined as all female subjects who have reached menarche and are not two years postmenopausal or who have reached menarche and have not had a hysterectomy, bilateral tubal ligation, and/or complete bilateral oophorectomy

Exclusion Criteria:

• Subjects who do not have a normally functioning HPA axis (as defined in the inclusion criteria).
• Subjects with an abnormal sleep schedule or who work at night.
• Subjects who have used topical dermal corticosteroids or topical immunomodulators (e.g., tacrolimus or pimecrolimus) within 3 weeks before Day 1, and subjects who are using any systemic medication known to affect cortisol levels or HPA axis integrity, systemic corticosteroids, an acute systemic course of corticosteroids, and/or any biological medication within 30 days before Day 1.
• Subjects with concomitant medical or dermatologic disorders (neurodermatitis, skin atrophy, striae, telangiectasia, etc.) that may interfere with study objectives and/or evaluations.
• Subjects with active skin infection.
• Subjects with any known significant endocrinological disorder that may require prohibited treatment, any known underlying disease that the investigator deems uncontrolled and poses a safety risk for the subject while participating in the study, known sensitivity to any ingredient of the study preparation, or a history of adverse responses to topical or systemic steroid therapy.
• Subjects who are pregnant or nursing.
• Subjects who have used bleach baths, phototherapy, and/or tanning beds, and/or who have had excessive sun exposure within 1 week before Day 1 and/or are planning to use any of these during the study.
• Subjects who have participated in a clinical drug or device research study and/or used any investigational treatment within the last 30 days before Day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: clobetasol propionate topical oil; clobetasol propionate 0.05% topical oil applied as thin film twice daily for 2 weeks	Drug: Clobetasol propionate 0.05% Topical Oil; thin film application of the oil twice daily; Other Names: clobetasol propionate topical solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With HPA Axis Suppression - Serum Cortisol Concentration (Cortrosyn Stimulation Test)	30-minute Post-stimulation cortisol level ≤18 µg/100 mL at Day 0 means subject is not enrolled; 30-minute Post-stimulation cortisol level ≤18 µg/100 mL at end of treatment (Day 15) means subject had suppression.	day 0 and day 15.
Adverse Events, Including Treatment Emergent Adverse Events (TEAEs)	number of events and percentage of subjects with AEs including TEAEs	Days 0, 1, 8 and 15

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ISGA Category	ISGA results will be summarized at each visit as: number and percentage of subjects in each ISGA category; number and percentage of subjects with an ISGA score of either 0 or 1 (clear or almost clear); number and percentage of subjects with an ISGA improvement of at least 2 grades from Baseline to each post-baseline evaluation; number and percentage of subjects with an ISGA score of either 0 or 1 (clear or almost clear) and an improvement of at least 2 grades from Baseline to each post-Baseline evaluation	Days 0, 1, 8 and 15 Efficacy assessment, including ISGA, was not performed due to premature termination of the study.
Assessment of Burning/Stinging, Skin Atrophy, Striae, Folliculitis, and Telangiectasias (Tolerability Parameters).	The subject will rate the sensation of burning/stinging within the past 24 hours as none (0), mild (1), moderate (2) or severe (3), and the Investigator will assess skin atrophy, striae, folliculitis, and telangiectasias, as absent (0) or present (1).	Days 1, 8 and 15

Collaborators and Investigators

• Sponsor: Hill Dermaceuticals, Inc.
• Collaborators: Covance; Synteract, Inc.
• Investigators: Study Director: Rosario G Ramirez, MD, Hill Dermaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2019
• Primary Completion (Actual): May 2, 2020
• Study Completion (Actual): July 28, 2020

Study Registration Dates

• First Submitted: January 23, 2019
• First Submitted That Met QC Criteria: February 18, 2019
• First Posted (Actual): February 20, 2019

Study Record Updates

• Last Update Posted (Actual): June 23, 2021
• Last Update Submitted That Met QC Criteria: June 1, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic; Physiological Effects of Drugs; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Clobetasol
• Other Study ID Numbers: CP0418 SS-P2 051

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No