Pharmacokinetics Study of Colchicine in Familial Mediterranean Fever (FMF) Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Open-label, Parallel-group, Multiple-Dose, Pharmacokinetic and Safety Study of Colchicine Pediatric Formulation in Pediatric and Adult Patients With FMF

Conditions
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Familial Mediterranean Fever

Intervention / Treatment
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* Drug: colchicine sprinkle capsules
* Drug: colchicine sprinkle capsules


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colchicine<br>Colchicine Sprinkle Capsules, 0.3 mg - dose administered according to age range on Day 1 | Drug: colchicine sprinkle capsules<br>* 0.3 mg<br>|
| Experimental: colchicine at steady state<br>colchicine sprinkle capsules 0.3 mg - dose administered according to age range on Day 15 following once daily dosing of colchicine on Days 2 - 14 | Drug: colchicine sprinkle capsules<br>* 0.3 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration | 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 | 15 days | 
| Area Under the Concentration Time Curve from Time Zero to the Time of Last Measured Concentration (AUC 0-t) | 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. | 15 days | 
| Area Under the Concentration Time Curve from Zero through Infinity | 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 | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Phase Reactant (ESR, CRP, SAA) Levels | Pharmacodynamic samples collected pre-dose on Days 7, 1 and 15 | 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics