Clinical trial NCT01075906: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Familial Mediterranean Fever
Keywords: pharmacokinetics
Lead sponsor: Mutual Pharmaceutical Company, Inc.
Sponsor class: INDUSTRY
First posted: 2010-02-25
Enrollment: 75
Sex: ALL
Minimum age (years): 2
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Maximum Plasma Concentration
timeFrame: 15 days
measure: Area Under the Concentration Time Curve from Time Zero to the Time of Last Measured Concentration (AUC 0-t)
timeFrame: 15 days
measure: Area Under the Concentration Time Curve from Zero through Infinity
timeFrame: 15 days
Secondary outcomes:
measure: Acute Phase Reactant (ESR, CRP, SAA) Levels
timeFrame: 15 days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Childrens Hospital Los Angeles
state: California
city: Yerevan
country: Armenia
facility: Center of Medical Genetics and Primary Health Care
city: Beer Sheba
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Pediatric Rheumatology Unit - Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Tel Hashomer
country: Israel
facility: Safra Children's Hospital
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center
city: Ankara
country: Turkey
facility: Hacettepe University
city: Istanbul
country: Turkey
facility: Cerrahpasa Medical Facility
Study officials:
affiliation: Mutual Pharmaceutical Company, Inc.
name: Matthew Davis, MD
role: STUDY_CHAIR
References: