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

Primary Outcome Measures:

• Maximum Plasma Concentration [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 Outcome Measures:

• Acute Phase Reactant (ESR, CRP, SAA) Levels [ Time Frame: 15 days ]
  Pharmacodynamic samples collected pre-dose on Days 7, 1 and 15
  
  

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.