Clinical trial NCT03847389: Clobetasol Topical Oil for Children With Moderate to Severe Atopic Dermatitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Atopic Dermatitis
Lead sponsor: Hill Dermaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Synteract, Inc.
name: Covance
First posted: 2019-02-20
Enrollment: 8
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: open-label, maximal use, in 3 successive age cohorts
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With HPA Axis Suppression - Serum Cortisol Concentration (Cortrosyn Stimulation Test)
timeFrame: day 0 and day 15.
measure: Adverse Events, Including Treatment Emergent Adverse Events (TEAEs)
timeFrame: Days 0, 1, 8 and 15
Secondary outcomes:
Other outcomes:
measure: ISGA Category
timeFrame: Days 0, 1, 8 and 15 Efficacy assessment, including ISGA, was not performed due to premature termination of the study.
measure: Assessment of Burning/Stinging, Skin Atrophy, Striae, Folliculitis, and Telangiectasias (Tolerability Parameters).
timeFrame: Days 1, 8 and 15
Locations:
city: Sanford
country: United States
facility: International Clinical Research - US, LLC
state: Florida
city: Savannah
country: United States
facility: AeroAllergy Research Laboratories of Savannah, Inc
state: Georgia
city: Philadelphia
country: United States
facility: Paddington Testing Co., Inc.
state: Pennsylvania
city: Spartanburg
country: United States
facility: Spartanburg Medical Research
state: South Carolina
city: San Antonio
country: United States
facility: Progressive Clinical Research
state: Texas
city: Richmond
country: United States
facility: Clinical Research Partners, LLC
state: Virginia
Study officials:
affiliation: Hill Dermaceuticals, Inc.
name: Rosario G Ramirez, MD
role: STUDY_DIRECTOR
References: