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

Familial Mediterranean Fever Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01075906
• Other study ID #: MPC-006-09-1001
• Status: Completed
• Phase: Phase 1
• First received: February 24, 2010
• Last updated: January 9, 2012
• Start date: August 2010
• Est. completion date: December 2011

Study information

• Verified date: January 2012
• Source: Mutual Pharmaceutical Company, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ethics CommissionUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 2 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Brucellosis
• Familial Mediterranean Fever
• Hereditary Autoinflammatory Diseases

Intervention

Drug:
• colchicine sprinkle capsules
0.3 mg
• colchicine sprinkle capsules
0.3 mg

Locations

Country	Name	City	State
Armenia	Center of Medical Genetics and Primary Health Care	Yerevan
Israel	Soroka Medical Center	Beer Sheba
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Pediatric Rheumatology Unit - Shaare Zedek Medical Center	Jerusalem
Israel	Safra Children's Hospital	Tel Hashomer
Israel	Sheba Medical Center	Tel Hashomer
Turkey	Hacettepe University	Ankara
Turkey	Cerrahpasa Medical Facility	Istanbul
United States	Childrens Hospital Los Angeles	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Mutual Pharmaceutical Company, Inc.

Countries where clinical trial is conducted

United States,  Armenia,  Israel,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	Acute Phase Reactant (ESR, CRP, SAA) Levels	Pharmacodynamic samples collected pre-dose on Days 7, 1 and 15	15 days	No