Brief Title
Pharmacokinetics Study of Colchicine in Familial Mediterranean Fever (FMF) Patients
Official Title
An Open-label, Parallel-group, Multiple-Dose, Pharmacokinetic and Safety Study of Colchicine Pediatric Formulation in Pediatric and Adult Patients With FMF
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Maximum Plasma Concentration
Secondary Outcome
Acute Phase Reactant (ESR, CRP, SAA) Levels
Condition
Familial Mediterranean Fever
Intervention
colchicine sprinkle capsules
Study Arms / Comparison Groups
Colchicine
Description: Colchicine Sprinkle Capsules, 0.3 mg - dose administered according to age range on Day 1
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
75
Start Date
August 2010
Completion Date
December 2011
Primary Completion Date
December 2011
Eligibility 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.
Gender
All
Ages
2 Years - 65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Matthew Davis, MD, ,
Location Countries
Armenia
Location Countries
Armenia
Administrative Informations
NCT ID
NCT01075906
Organization ID
MPC-006-09-1001
Responsible Party
Sponsor
Study Sponsor
Mutual Pharmaceutical Company, Inc.
Study Sponsor
Matthew Davis, MD, Study Chair, Mutual Pharmaceutical Company, Inc.
Verification Date
January 2012