Familial Mediterranean Fever
Conditions
Keywords
pharmacokinetics
Brief summary
Colchicine is widely recognized as safe and effective treatment of Familial Mediterranean Fever (FMF) in children and adults. Colchicine is currently used to treat FMF in younger patients by inexact dosing through breaking or crushing adult-dose tablets. An age-appropriate sprinkle formulation will allow for more accurate dosing in pediatric patients. The primary objective of this study is to evaluate and compare the steady-state pharmacokinetics of multiple oral doses of colchicine sprinkle capsules administered to pediatric and adult FMF patients. Secondary objectives include evaluation of the safety and tolerability of this regimen in pediatric and adult FMF patients and measurement of the levels of acute phase reactants (i.e, serum amyloid A \[SAA\], erythrocyte sedimentation rate \[ESR\], C-reactive protein \[CRP\]) at baseline and after dosing.
Detailed description
FMF patients who have not been taking colchicine (colchicine-naïve patients) will be enrolled into a 1 week dose-titration period (Days -7 to -1). Beginning on Day -7, a pre-dose blood sample will be collected from the colchicine-naïve patient population for determination of pharmacodynamic markers. Patients will then be administered a low starting dose of colchicine (as determined by the principal investigator) titrated up to the study colchicine dose which is 0.6 mg (2 capsules) in children ≥2 to \< 6 years old, 0.9 mg (3 capsules) in children ≥6 to \< 12, 1.2 mg (4 capsules) in children ≥12 to \< 16 and adults ≥16 and \< 65. On Day 2, patients will return to the clinic for collection of a pre-dose blood sample followed by administration of the study dose of colchicine. On Days 3-7, patients (parent/guardian) will self-medicate with the study dose of colchicine recording the time of dosing and any adverse events. On Days 8-14, patients (parent/guardian) will self-medicate with the study dose of colchicine recording the time of dosing and any adverse events. On the morning of Day 15, patients will return to the clinic for collection of a pre-dose blood sample followed by administration of the study dose of colchicine. Blood samples will be collected post-dose at times sufficient to adequately define the pharmacokinetics of colchicine and its metabolites. Safety and tolerability of this dosing regimen will be determined by evaluation of vital signs and adverse events during the study and upon completion of the study. All adverse events will be evaluated by the investigator and reported in the subject's case report form.
Interventions
DRUGcolchicine sprinkle capsules
0.3 mg
Sponsors
Mutual Pharmaceutical Company, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Patients age 2-65 years with a confirmed clinical diagnosis of FMF, * Non-pregnant, and * If of child-bearing potential, using effective contraceptive measures.
Exclusion criteria
* Recent participation (within 30 days) in other research studies, * Pregnant or lactating, * History or current infection of human immunodeficiency virus (HIV), hepatitis A, B or C, * Current or recent use of any drugs/drug classes or combinations thereof that may affect the absorption or metabolism of colchicine, * Clinically relevant abnormal clinical laboratories at screening, * Current or recent (\<6 months) history of severe, unstable or uncontrolled neurological, cardiovascular, gastrointestinal, hematological, moderate or severe hepatic and/or renal disease, or evidence of other diseases at the physical examination conducted at the screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration | 15 days | pharmacokinetic samples collected pre-dose on Days 1, 2 and 15 and at 0.25 - 0.5 hours, 1.5-2.5 hours and at 5-8 hours post-dose on Days 1 and 15 |
| Area Under the Concentration Time Curve from Time Zero to the Time of Last Measured Concentration (AUC 0-t) | 15 days | Pharmacokinetic samples collected pre-dose on Days 1,2 and 15 and at 0.25-0.5 hours, 1.5-2.5 hours and 5-8 hours post-dose on Days 1 and 15. |
| Area Under the Concentration Time Curve from Zero through Infinity | 15 days | Pharmacokinetic samples collected pre-dose on Days 1, 2 and 15 and at 0.25-0.5 hours, 1.5-2.5 hours and at 5-8 hours post-dose on Days 1 and 15 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute Phase Reactant (ESR, CRP, SAA) Levels | 15 days | Pharmacodynamic samples collected pre-dose on Days 7, 1 and 15 |
Countries
Armenia, Israel, Turkey (Türkiye), United States
Outcome results
None listed