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

Phase 1

Completed

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

Brief Summary: 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.

Detailed 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Cohort 1 (Adolescents, Adults)	Diacerein 1% Ointment	Adolescent and adult subjects with EB (aged 12 years and older) received diacerein 1% ointment daily for 10 days.
Cohort 2 (Children)	Diacerein 1% Ointment	Children with EB (aged 4 to 11 years, inclusive) received diacerein 1% ointment daily for 10 days.

Primary Outcome Measures

Name	Time	Method
Detectable Plasma Concentrations of Diacerein and Rhein	Days 1-10, at select time points per protocol	Bioanalytical analyses were performed to determine concentrations levels of diacerein and rhein in plasma using validated bioanalytical methods. For Cohort 1, blood samples were taken at pre-dose and 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose. For Cohort 2, blood samples were taken at pre-dose and 1, 2, 4, 6, and 8 hours post-dose. Trough PK samples were collected on any 2 available days from Days 3 through 9 for Cohort 1 only. Summary statistics for each scheduled time were only reported if at least 50% of subjects had quantifiable concentrations.

Secondary Outcome Measures

Name	Time	Method

Locations (3): Stanford School of Medicine
🇺🇸
Palo Alto, California, United States
UNC Dermatology
🇺🇸
Chapel Hill, North Carolina, United States
Northwestern University Medical Center
🇺🇸
Chicago, Illinois, United States