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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Familial Mediterranean Fever	Drug: colchicine sprinkle capsules	Phase 1

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	75 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Basic Science
Official Title:	An Open-label, Parallel-group, Multiple-Dose, Pharmacokinetic and Safety Study of Colchicine Pediatric Formulation in Pediatric and Adult Patients With FMF
Study Start Date :	August 2010
Actual Primary Completion Date :	December 2011
Actual Study Completion Date :	December 2011

Arms and Interventions

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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

Outcome Measures

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Primary Outcome Measures :

1. 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
2. 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.
3. 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 :

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

Eligibility Criteria

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Ages Eligible for Study:	2 Years to 65 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

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.

Contacts and Locations

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Locations

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

Sponsors and Collaborators

Mutual Pharmaceutical Company, Inc.

Investigators

Study Chair:	Matthew Davis, MD	Mutual Pharmaceutical Company, Inc.

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier:	NCT01075906 History of Changes
Other Study ID Numbers:	MPC-006-09-1001
First Posted:	February 25, 2010
Last Update Posted:	January 10, 2012
Last Verified:	January 2012

Keywords provided by Mutual Pharmaceutical Company, Inc.:

pharmacokinetics

Additional relevant MeSH terms:

Fever; Brucellosis; Familial Mediterranean Fever; Hereditary Autoinflammatory Diseases; Body Temperature Changes; Signs and Symptoms; Gram-Negative Bacterial Infections; Bacterial Infections; Genetic Diseases, Inborn; Skin Diseases, Genetic	Skin Diseases; Colchicine; Gout Suppressants; Antirheumatic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents