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

NCT ID: NCT01075906

Last Updated: 2012-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2011-12-31

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.

Conditions

Familial Mediterranean Fever

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Colchicine

Colchicine Sprinkle Capsules, 0.3 mg - dose administered according to age range on Day 1

Group Type: EXPERIMENTAL

colchicine sprinkle capsules

Intervention Type: DRUG

0.3 mg

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

Group Type: EXPERIMENTAL

colchicine sprinkle capsules

Intervention Type: DRUG

0.3 mg

Interventions

colchicine sprinkle capsules

0.3 mg

Intervention Type: DRUG

colchicine sprinkle capsules

0.3 mg

Intervention Type: DRUG

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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Mutual Pharmaceutical Company, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthew Davis, MD

Role: STUDY_CHAIR

Mutual Pharmaceutical Company, Inc.

Locations

Childrens Hospital Los Angeles

Los Angeles, California, United States

Center of Medical Genetics and Primary Health Care

Yerevan, Yerevan, Armenia

Soroka Medical Center

Beersheba, Beer Sheba, Israel

Rambam Medical Center

Haifa, Haifa District, Israel

Hadassah Medical Center

Jerusalem, Israel, Israel

Pediatric Rheumatology Unit - Shaare Zedek Medical Center

Jerusalem, Jerusalem, Israel

Safra Children's Hospital

Tel Litwinsky, Tel Hashomer, Israel

Sheba Medical Center

Tel Litwinsky, Tel Hashomer, Israel

Hacettepe University

Ankara, Ankara, Turkey (Türkiye)

Cerrahpasa Medical Facility

Istanbul, Istanbul, Turkey (Türkiye)

Countries

United States; Armenia; Israel; Turkey (Türkiye)

Other Identifiers

MPC-006-09-1001

Identifier Type: -

Identifier Source: org_study_id