An Open-Label Safety Study to Assess the Multiple-Dose Pharmacokinetics and Potential for Adrenal Suppression Following Topical Treatment With Halobetasol Propionate 0.05% Topical Spray (Sun Pharmaceuticals Industries Limited) in Patients With Moderate to Severe Atopic Dermatitis
Overview
- Phase
- Phase 2
- Intervention
- Treatment with Halobetasol propionate 0.05% topical spray
- Conditions
- Atopic Dermatitis
- Sponsor
- Sun Pharmaceutical Industries Limited
- Enrollment
- 20
- Locations
- 13
- Primary Endpoint
- Change from baseline in the IGA score at Days 4, 5, 7 and 14.
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
Brief Summary
This is an open-label, safety study designed to assess the multiple-dose pharmacokinetics and potential for adrenal suppression following topical treatment with halobetasol propionate 0.05% spray applied twice-daily in adult patients with moderate to severe atopic dermatitis. At least 40 eligible patients with atopic dermatitis that satisfy all eligibility criteria will be enrolled into the study
Detailed Description
This is an open-label, safety study designed to assess the multiple-dose pharmacokinetics and potential for adrenal suppression following topical treatment with halobetasol propionate 0.05% spray applied twice-daily in adult patients with moderate to severe atopic dermatitis. At least 40 eligible patients with atopic dermatitis that satisfy all eligibility criteria will be enrolled into the study. Patients must be overall in good health and should have a current diagnosis of moderate to severe atopic dermatitis with Investigator Global Assessment (IGA) score of at least 3 or 4. Patients will be stratified by age with: Cohort 1: At least 20 patients 18 years of age and older with ≥ 25% BSA affected. Cohort 2: At least 20 patients 12-16 years and 11 months of age with ≥ 25% BSA affected. Cohort 2 will initiate enrollment once all enrolled patients in Cohort 1 have completed the study and a safety analysis has been reviewed by the Medical Monitor and approved by the Novum Independent Institutional Review Board (NIIRB). Sites will not begin enrollment of patients in Cohort 2 until the site is notified by email that the safety analysis for Cohort 1 has been reviewed and approved. Each cohort will be enrolled based on the availability of patients. Each cohort will be reviewed for the potential of HPA axis suppression. The Medical Monitor or NIIRB may discontinue the study at any time if safety concerns are found. If 6 or more patients in Cohort 1 experience HPA axis suppression, then enrollment for Cohort 1 will be stopped. Cohort 2 will not be initiated if 6 or more patients enrolled in Cohort 1 experience HPA axis suppression or 30% or more of the final enrolled number of patients in Cohort 1 experience HPA axis suppression. If 6 or more patients in Cohort 2 experience HPA axis suppression, then enrollment for Cohort 2 will be stopped. If the study is stopped at any time, patients currently enrolled will be contacted via phone and instructed to discontinue study product immediately. Patients will be instructed to return for their next scheduled visit for cortisol response testing. Sites will follow up with patients and monitor for HPA axis suppression. All patients will be followed until cortisol levels are normal, as defined in study protocol. Patients enrolled in the study will apply the study product twice daily onto the affected skin areas for 14 days (Days 1-14), according to provided instructions. .Patients will be instructed not to rub over the affected area after application of spray. Each patient is expected to receive 28 doses of study product. All patients will attend the clinic for the following 8 scheduled visits. Patients will apply the morning dose of the study product in the clinic at each clinic visit (and evening dose on Day 4) and at home during non-clinic visits. A phone call will be made approximately 14 days after the patient has completed dosing to follow-up on any new adverse events that may have occurred. All patients will have a cortisol response test performed at screening and on Day 17 (at least 48 hours after last dose of study product). The safety profile of the test product will be evaluated by analysis of reported adverse events.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males or non-pregnant, non-lactating females:
- •Cohort 1: 18 years of age and older
- •Cohort 2: 12-16 years and 11 months of age (Cohort 2 will not begin enrollment until review and approval of safety information from Cohort 1.)
- •If female and of childbearing potential, prepared to abstain from sexual intercourse or use a reliable method of contraception during the study (e.g., condom, IUD, oral, transdermal or injected hormonal contraceptives). Female patients using hormonal contraceptives should have been on the same product/dosing regimen for at least 28 days before baseline and should not change this regimen during the study.
- •Signed informed consent form that meets all criteria of current FDA regulations. For a patient considered to be a minor in the state he/she lives and is enrolled, the parent or legal guardian will be required to sign the consent form and the patient will sign an IRB approved "assent to participate" form. Approved informed consent and assent forms specific to each cohort will be required.
- •Patients with a definite clinical diagnosis of moderate to severe atopic dermatitis with ≥ 25% BSA affected (excluding face, scalp, groin, axillae and other intertriginous areas)
- •Investigator Global Assessment (IGA) score of 3 (Moderate) or 4 (Severe).
- •Patients in Cohort 2 must weigh a minimum of 26 kg.
- •Results from a cortisol response test that are considered normal and show no evidence of any abnormal HPA function or adrenal response. Patients must fulfill all of the following stipulations:
- •Basal (pre Cortrosyn™ injection) cortisol concentration ≥ 5 mcg/100 mL.
Exclusion Criteria
- •Females who are pregnant, nursing, planning to become pregnant during the duration of the study, or if of childbearing potential and sexually active and not prepared to use appropriate contraceptive methods to avoid pregnancy.
- •Mild atopic dermatitis.
- •IGA score \<
- •Atopic dermatitis with a BSA involvement \< 25%.
- •Results from a cortisol response test that show evidence of any abnormal HPA function or adrenal response:
- •Basal (pre CortrosynTM injection) cortisol concentration \< 5 mcg/100 mL.
- •30 minute post-injection cortisol level is less than 7 mcg/100 mL greater than the basal level (\< basal value + 7).
- •Post-stimulation level ≤ 18 mcg/100 mL.
- •Recurrent or active cutaneous bacterial or viral infection in any treatment area at baseline (i.e., clinically infected atopic dermatitis).
- •Patient has a history of atopic dermatitis that has been unresponsive to topical corticosteroid therapy.
Arms & Interventions
Treatment with topical halobetasol spray 0.05%
Patients will instructed o apply halobetasol spray twice daily for 14 days and not to rub over the affected area after application of spray.
Intervention: Treatment with Halobetasol propionate 0.05% topical spray
Outcomes
Primary Outcomes
Change from baseline in the IGA score at Days 4, 5, 7 and 14.
Time Frame: 14 days
Patients will be considered to have shown improvement in disease severity if the IGA score decreases by at least one unit from the baseline score, and will be considered a treatment success if the IGA score is either 0 (clear) or 1 (almost clear).
Secondary Outcomes
- Hypothalamic Pituitary Adrenal (HPA) Axis suppression(14 days)