Dystrophic Epidermolysis Bullosa, Epidermolysis Bullosa (EB), Epidermolysis Bullosa Simplex, Junctional Epidermolysis Bullosa
Conditions
Keywords
EB, EBS, DEB, JEB
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.
Interventions
Diacerein 1% Ointment administered topically
Sponsors
Castle Creek Pharmaceuticals, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (Adolescents, Adults) Adolescent and adult patients with EB (aged 12 and older) received Diacerein 1% Ointment daily for 10 days. | 8 |
| Cohort 2 (Children) Children with EB (aged 4 to 11 years, inclusive) received Diacerein 1% Ointment daily for 10 days. | 3 |
| Total | 11 |
Baseline characteristics
| Characteristic | Cohort 1 (Adolescents, Adults) | Total | Cohort 2 (Children) |
|---|---|---|---|
| Age, Continuous | 26.5 years STANDARD_DEVIATION 11.74 | 21.5 years STANDARD_DEVIATION 13 | 8.3 years STANDARD_DEVIATION 1.53 |
| EB Classification per Cohort Dystrophic Epidermolysis Bullosa (DEB) | 4 participants | 4 participants | 0 participants |
| EB Classification per Cohort Epidermolysis Bullosa Simplex (EBS) | 4 participants | 7 participants | 3 participants |
| EB Classification per Cohort Junctional Epidermolysis Bullosa (JEB) | 0 participants | 0 participants | 0 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 8 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 9 Participants | 2 Participants |
| Region of Enrollment United States | 8 Participants | 11 Participants | 3 Participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 3 |
| other Total, other adverse events | 1 / 8 | 0 / 3 |
| serious Total, serious adverse events | 0 / 8 | 0 / 3 |
Outcome results
Primary
Detectable Plasma Concentrations of Diacerein and Rhein
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.
Time frame: Days 1-10, at select time points per protocol
Population: Cohort 1: 4 adolescent/adult subjects with EBS, 4 adolescent/adult subjects with DEB; Cohort 2: 3 child subjects with EBS
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 (Adolescents, Adults) | Detectable Plasma Concentrations of Diacerein and Rhein | Rhein Above Lower limit of quantification:DEB | 4 Participants |
| Cohort 1 (Adolescents, Adults) | Detectable Plasma Concentrations of Diacerein and Rhein | Rhein Below the limit of quantification:DEB | 0 Participants |
| Cohort 1 (Adolescents, Adults) | Detectable Plasma Concentrations of Diacerein and Rhein | Diacerein Below the limit of quantification:DEB | 4 Participants |
| Cohort 1 (Adolescents, Adults) | Detectable Plasma Concentrations of Diacerein and Rhein | Rhein Above Lower limit of quantification:EBS | 1 Participants |
| Cohort 1 (Adolescents, Adults) | Detectable Plasma Concentrations of Diacerein and Rhein | Diacerein Below the limit of quantification:EBS | 4 Participants |
| Cohort 1 (Adolescents, Adults) | Detectable Plasma Concentrations of Diacerein and Rhein | Diacerein Above Lower limit of quantification:EBS | 0 Participants |
| Cohort 1 (Adolescents, Adults) | Detectable Plasma Concentrations of Diacerein and Rhein | Rhein Below the limit of quantification:EBS | 3 Participants |
| Cohort 1 (Adolescents, Adults) | Detectable Plasma Concentrations of Diacerein and Rhein | Diacerein Above Lower limit of quantification:DEB | 0 Participants |
| Cohort 2 (Children) | Detectable Plasma Concentrations of Diacerein and Rhein | Rhein Below the limit of quantification:EBS | 2 Participants |
| Cohort 2 (Children) | Detectable Plasma Concentrations of Diacerein and Rhein | Rhein Above Lower limit of quantification:DEB | 0 Participants |
| Cohort 2 (Children) | Detectable Plasma Concentrations of Diacerein and Rhein | Diacerein Below the limit of quantification:EBS | 3 Participants |
| Cohort 2 (Children) | Detectable Plasma Concentrations of Diacerein and Rhein | Diacerein Above Lower limit of quantification:DEB | 0 Participants |
| Cohort 2 (Children) | Detectable Plasma Concentrations of Diacerein and Rhein | Rhein Above Lower limit of quantification:EBS | 1 Participants |
| Cohort 2 (Children) | Detectable Plasma Concentrations of Diacerein and Rhein | Rhein Below the limit of quantification:DEB | 0 Participants |
| Cohort 2 (Children) | Detectable Plasma Concentrations of Diacerein and Rhein | Diacerein Below the limit of quantification:DEB | 0 Participants |
| Cohort 2 (Children) | Detectable Plasma Concentrations of Diacerein and Rhein | Diacerein Above Lower limit of quantification:EBS | 0 Participants |