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

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

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.

Study Overview

• Status: Completed
• Conditions: Familial Mediterranean Fever
• Intervention / Treatment: Drug: colchicine sprinkle capsules

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.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• Armenia
  • Yerevan, Armenia, 0010
    • Center of Medical Genetics and Primary Health Care
• Israel
  • Beer Sheba, Israel, 84141
    • Soroka Medical Center
  • Haifa, Israel, 24035
    • Rambam Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center
  • Jerusalem, Israel, 91031
    • Pediatric Rheumatology Unit - Shaare Zedek Medical Center
  • Tel Hashomer, Israel, 52621
    • Sheba Medical Center
  • Tel Hashomer, Israel, 52621
    • Safra Children's Hospital
• Turkey
  • Ankara, Turkey, 06100
    • Hacettepe University
  • Istanbul, Turkey, 34303
    • Cerrahpasa Medical Facility
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Childrens Hospital Los Angeles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Colchicine; Colchicine Sprinkle Capsules, 0.3 mg - dose administered according to age range on Day 1	Drug: colchicine sprinkle capsules; 0.3 mg
Experimental: colchicine at steady state; 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; 0.3 mg

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mutual Pharmaceutical Company, Inc.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: February 24, 2010
• First Submitted That Met QC Criteria: February 24, 2010
• First Posted (Estimate): February 25, 2010

Study Record Updates

• Last Update Posted (Estimate): January 10, 2012
• Last Update Submitted That Met QC Criteria: January 9, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: pharmacokinetics
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Genetic Diseases, Inborn; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Skin Diseases, Genetic; Body Temperature Changes; Fever; Brucellosis; Familial Mediterranean Fever; Hereditary Autoinflammatory Diseases; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: MPC-006-09-1001