Evaluation of Absorption, Systemic Pharmacokinetics, and HPA Axis Suppression of Topical IDP-118 Lotion in Pediatric Moderate to Severe Plaque Psoriasis

Trial ID: 2024-520057-20-00
Protocol: V01-118A-401
Sponsor: Bausch Health Americas Inc.

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Diseases & Conditions

Psoriasis

Objectives

The primary objective of this study is to evaluate the **safety** of IDP-118 Lotion, which contains **halobetasol propionate** 0.01% and **tazarotene** 0.045%, when administered topically once daily for 8 weeks in pediatric subjects with moderate to severe **plaque psoriasis**. This is clinically relevant as it assesses the potential adverse effects and tolerability of the treatment in a vulnerable population. Additionally, the study aims to determine the systemic exposure of halobetasol propionate and tazarotene from IDP-118 Lotion when applied once daily for 4 weeks, which is crucial for understanding the pharmacokinetic profile and ensuring systemic safety. Another primary objective is to assess the potential for **HPA axis suppression** when the lotion is applied once daily for 8 weeks, which is important for evaluating the risk of systemic corticosteroid effects.

Participants

The clinical trial involves a total of **19 participants** diagnosed with **plaque psoriasis**. The study population comprises both male and female subjects, aged between 12 to 16 years and 11 months, who are in good general health. Participants were selected based on their willingness to comply with study instructions and their ability to return for required visits. The trial excludes vulnerable populations and focuses on individuals with a clinical diagnosis of psoriasis, specifically those with an Investigator’s Global Assessment (IGA) score of 3 or 4, excluding the face, scalp, axillae, and intertriginous areas. Participants must have an area of plaque psoriasis suitable for topical treatment involving at least 10% of their body surface area. Lifestyle considerations include avoiding prolonged exposure of the treatment area to ultraviolet radiation. Female participants of childbearing potential are required to practice effective contraception throughout the study duration. The trial ensures that all participants are in good general adrenal health, as determined by specific serum cortisol levels, and have normal or non-clinically significant hematology and serum chemistry laboratory values.

Plans and Procedures

The clinical trial is designed to evaluate the **absorption**, systemic pharmacokinetics, and hypothalamic-pituitary-adrenal (HPA) axis suppression potential of a topically applied formulation, IDP-118 Lotion, in pediatric subjects with moderate to severe **plaque psoriasis**. This is a Phase 4, open-label, multicenter study. The trial will involve the administration of IDP-118 Lotion, which contains the active substances **tazarotene** and **halobetasol propionate**, applied topically once daily for a period of 8 weeks. The primary objectives include assessing the safety of the lotion, its systemic exposure, and its potential to suppress the HPA axis.

Participants will be involved in the study for a total duration of 8 weeks, with the trial expected to conclude by May 31, 2025. The study will commence with a screening visit to confirm eligibility, which includes criteria such as age between 12 to 16 years, a clinical diagnosis of psoriasis with an Investigator’s Global Assessment score of 3 or 4, and a body surface area involvement of at least 10% excluding certain areas. Participants must also be in good general health and agree to avoid prolonged exposure to ultraviolet radiation.

Following the screening, eligible participants will proceed to the baseline visit, where the first application of the study drug will occur. Subsequent follow-up visits will be scheduled to monitor safety, efficacy, and any potential adverse effects. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted. Conditions that may lead to early termination from the study include non-compliance with study procedures, adverse events, or withdrawal of consent by the participant or their legal guardian.

Treatment

The clinical trial involves the use of **Duobrii**, a **cutaneous liquid** formulation, as the experimental medication. Duobrii contains two active chemical substances: **tazarotene** and **halobetasol propionate**. The pharmaceutical form of the medication is a topical liquid, designed for **topical use**. The dosage regimen for the trial specifies a maximum daily dose of 7 grams, with a total maximum dose of 392 grams over the course of the treatment period. The treatment is administered once daily for a duration of 8 weeks. The primary objective of the trial is to evaluate the safety, systemic exposure, and HPA axis suppression potential of the IDP-118 Lotion, which is the sponsor's product code for Duobrii.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are mentioned. The focus is solely on the administration of the experimental medication, Duobrii. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the once-daily application over the specified 8-week period. The trial aims to gather data on the absorption and systemic pharmacokinetics of the active substances when applied topically in pediatric subjects with moderate to severe plaque psoriasis.

Efficacy

Efficacy in this clinical trial will be assessed through the evaluation of the **systemic exposure** of the active substances, halobetasol propionate (HP) and tazarotene (Taz), as well as their metabolite, tazarotenic acid, following the topical application of IDP-118 Lotion. The primary endpoints include the measurement of systemic exposure levels and the potential for **hypothalamic-pituitary-adrenal (HPA) axis suppression** when the lotion is applied once daily. These assessments will be conducted over a treatment period of 8 weeks, with specific attention to the pharmacokinetics of the active substances. The trial will utilize validated laboratory tests to measure these parameters, ensuring accurate and reliable data collection. The schedule for these assessments will be aligned with the trial's protocol, focusing on the systemic absorption and potential endocrine effects of the treatment in pediatric subjects with moderate to severe plaque psoriasis.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Male or female, of any race, 12 to 16 years 11 months of age at the time of informed consent/assent obtained
Verbal and written informed consent/assent obtained from the subject and/or parent or legal guardian.
Has a clinical diagnosis of psoriasis at the Screening and Baseline visit with an Investigator’s Global Assessment (IGA) score of 3 or 4. The face, scalp, axillae, and intertriginous areas are to be excluded in this assessment, if psoriasis is present
Has an area of plaque psoriasis appropriate for topical treatment that involves a BSA of at least 10% at Screening and Baseline. The face, scalp, axillae, and intertriginous areas are to be excluded in this calculation.
Is willing and able to avoid prolonged exposure of the treatment area to ultraviolet radiation (natural and artificial) for the duration of the study.
Is in good general adrenal health, as determined by a 30-minute postcosyntropin stimulation serum cortisol level that is > 18 μg/dL at screening.
Is in good general health based on the subject’s medical history and a physical examination, with screening hematology and serum chemistry laboratory values within normal ranges or not clinically significant, as determined by the investigator
Pre-menses females (9 and older) and females of childbearing potential, must have a negative urine and serum pregnancy test at Screening and a negative urine pregnancy test at the Baseline visit prior to study drug application .
Females of childbearing potential and females who are pre-menses (9 and older) must be willing to practice effective contraception for the duration of the study. (Effective contraception is defined as stabilized on oral contraceptive for at least 3 months, IUD, condom with spermicidal, diaphragm with spermicidal, implant, Nuvaring, injection, transdermal patch or abstinence.). Females on birth control pills must have taken the same type pill for at least three months prior to entering the study and must not change type during the study. Those who have used birth control pills in the past must have discontinued usage at least three months prior to the start of the study.
Subject is willing to comply with study instructions and return to the clinic for required visits.

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Exclusion Criteria

Has spontaneously improving or rapidly deteriorating plaque psoriasis or pustular psoriasis, as determined by the investigator.
Has a history of adrenal disease.
Presents with any concurrent skin condition that could interfere with the evaluation of the treatment areas, as determined by the investigator.
Is pregnant, nursing an infant, or planning a pregnancy during the study period.
Has received treatment with any investigational drug or device within 60 days or 5 drug half-lives (whichever is longer) prior to baseline, or is concurrently participating in another clinical study with an investigational drug or device
Received treatment with a topical antipsoriatic drug product other than corticosteroids or Taz-based therapy within 14 days prior to the Baseline visit, and/or treatment containing Taz within 28 days prior to the Baseline visit, and/or treatment containing corticosteroids within 28 days prior to the screening HPA axis stimulation test
Has used any phototherapy (including laser), photochemotherapy, or systemic non-biologic psoriasis therapy (such as newer oral psoriasis medications [eg, Otezla], methotrexate, retinoids or cyclosporine) within 4 weeks prior to the Baseline visit, or systemic corticosteroids within 28 days prior to the screening HPA axis stimulation test.
Has used immunomodulatory therapy (e.g., biologics) known to affect psoriasis within 3 months of baseline.
Has had prolonged exposure to natural or artificial sources of ultraviolet radiation within 4 weeks prior to screening or is intending to have exposure during the study thought likely by the investigator to modify the subject’s psoriasis
Is currently using lithium or Plaquenil.
Has a history of hypersensitivity or allergic reaction to any of the study drug constituents.
Is unable to be compliant with study procedures, study drug administration requirements, study visit schedules, and prohibitions regarding the use of concomitant medications/therapies.
Is unable to communicate or cooperate with the investigator.
Has any underlying disease deemed uncontrolled by the investigator that poses a concern for the subject’s safety while participating in the study
Has a history of drug or alcohol abuse as determined by the investigator.
Is considered by the investigator, for any other reason, to be an unsuitable candidate for the study.
Has an abnormal sleep schedule or works at night.
Has a history of an adverse reaction to cosyntropin injection or similar test reagents.