To Evaluate the Pharmacokinetic of Diacerein and Rhein After Maximum Use in Patients With Epidermolysis Bullosa (EB)

Castle Creek Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Epidermolysis Bullosa (EB); Junctional Epidermolysis Bullosa; Dystrophic Epidermolysis Bullosa; Epidermolysis Bullosa Simplex

Treatments: Drug: Diacerein 1% Ointment

Study type: Interventional

Funder types: Industry

Identifiers

NCT03472287

CCP-020-101

Details and patient eligibility

About

A pharmacokinetic (PK) study in 16-20 EB subjects to be allocated to two cohorts. Cohort 1 to include 8-10 subjects (ages 12 yrs and older); Cohort 2 to include 8-10 subjects (ages 6 months-11 yrs, inclusive). Cohort 2 only included subjects 4 yrs and older. Serial PK blood sampling collected on Days 1 and 10. Analyses were performed to determine the concentrations of diacerein and rhein.

Full description

This was an open-label, single-period study that intended to include subjects with EB consisting of infants/ children (ages 6 months to 11 years, inclusive) and adolescents/ adults (ages 12 years and older). The study included 2 cohorts.

Cohort 1 was to include adolescent/adult subjects with EB (ages 12 years and older);

Cohort 2 was to include infants/children with EB (ages 4 to 11 years, inclusive).

For both cohorts, the study intended to enroll subjects with epidermolysis bullosa simplex (EBS), dystrophic epidermolysis bullosa (DEB), and junctional epidermolysis bullosa (JEB) with lesions encompassing >/=2% BSA. The diacerein application area was >/=5% BSA and included lesioned and non-lesioned skin (if lesions accounted for <5% BSA); however, topical administration was </=30% BSA. On Days 1 and 10, the topical dose of study drug was applied by study staff, and blood was sampled for PK analyses of diacerein and rhein pre-dose and through 8 hours post-application. On Days 2 to 9, study drug was applied to the application area(s) at home. For Cohort 1, trough PK samples were collected on any 2 available days from Days 3 through 9, and study drug was applied after blood draw, while for Cohort 2 trough PK analyses were not performed.

Enrollment: 11 patients

Sex: All

Ages: 4+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• At least 12 years of age (Cohort 1) or at least 6 months of age to 11 years, inclusive (Cohort 2) at screening. For US only: at least 4 years of age to 11 years, inclusive (Cohort 2)
• The subject must weigh at least 9 kg (19.8 lbs) at Screening.
• Subject has a documented genetic mutation consistent with EB.
• Subject has EB lesions on ≥ 2% body surface area (BSA) and the EB lesions are in the following body areas: a. Localized: plantar and/or palmar areas, b. Generalized: arms, legs, torso, hands and feet.

Key Exclusion Criteria:

• Subject has EB lesions where drug will be applied that are infected
• Subject has used any diacerein containing product within 1 month prior to Visit 1
• Subject has used systemic immunotherapy or cytotoxic chemotherapy within 60 days prior to dosing.
• Subject has used systemic steroidal therapy or has used topical steroidal therapy on the EB lesions in the application area within 14 days prior to dosing
• Subject has participated in an investigational drug trial in which administration of an investigational study medication occurred within 30 days prior to dosing

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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11 participants in 2 patient groups

Cohort 1 (Adolescents, Adults)

Experimental group

Description:

Adolescent and adult subjects with EB (aged 12 years and older) received diacerein 1% ointment daily for 10 days.

Treatment:

Drug: Diacerein 1% Ointment

Cohort 2 (Children)

Experimental group

Description:

Children with EB (aged 4 to 11 years, inclusive) received diacerein 1% ointment daily for 10 days.

Treatment:

Drug: Diacerein 1% Ointment