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 Applied Twice Daily for 28 Days in Patients With Moderate to Severe Plaque Psoriasis
Overview
- Phase
- Phase 2
- Intervention
- Halobetasol Propionate
- Conditions
- Plaque Psoriasis
- Sponsor
- Sun Pharmaceutical Industries Limited
- Primary Endpoint
- Change from baseline in the IGA score at Day 28
- Status
- Withdrawn
- Last Updated
- 4 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 plaque psoriasis. At least 40 eligible patients with plaque psoriasis 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 plaque psoriasis. At least 40 eligible patients with plaque psoriasis 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 plaque psoriasis 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 ≥ 20% body surface area (BSA) affected Cohort 2: At least 20 patients 12-16 years and 11 months of age with ≥ 10% 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. Confirmation of email receipt will be required from each Investigator before enrollment of Cohort 2 can begin. 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. Patients will be instructed to apply topical spray twice daily onto the affected skin areas for 28 days. Patients will be instructed not to rub over the affected area after application of spray Patients will apply the morning dose of the study product in the clinic at each clinic visit 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
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 stable plaque psoriasis with:
- •Cohort 1: 18 years of age and older with ≥ 20% BSA affected (excluding the face, scalp, groin, axillae and other intertriginous areas)
- •Cohort 2: 12-16 years and 11 months of age with ≥ 10% BSA affected (excluding the 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 24 kg.
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.
- •Lacks stable diagnosis of plaque psoriasis or has been diagnosed with mild plaque psoriasis.
- •IGA score \<
- •Plaque psoriasis with a BSA involvement \< 20% for Cohort 1 or \< 10% for Cohort
- •Current diagnosis of types of psoriasis other than stable plaque psoriasis (i.e., erythrodermic, exfolative or pustular psoriasis).
- •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.
- •Patient has a history of plaque psoriasis that has been unresponsive to topical corticosteroid therapy.
Arms & Interventions
Halobetasol propionate 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: Halobetasol Propionate
Outcomes
Primary Outcomes
Change from baseline in the IGA score at Day 28
Time Frame: 28 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 (minimal).
Secondary Outcomes
- Hypothalamic Pituitary Adrenal (HPA) Axis suppression(28 days)