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

• ClinicalTrials.gov Identifier: NCT01075906
• Recruitment Status: Completed
• First Posted: February 25, 2010
• Last Update Posted: January 10, 2012
• Sponsor: Mutual Pharmaceutical Company, Inc.
• Information provided by (Responsible Party): Mutual Pharmaceutical Company, Inc.

Study Description

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

• 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

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

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

• Ages Eligible for Study: 2 Years to 65 Years (Child, Adult, Older 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

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

• Responsible Party: Mutual Pharmaceutical Company, Inc.
• ClinicalTrials.gov Identifier: NCT01075906
• 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:

Brucellosis; Familial Mediterranean Fever; Hereditary Autoinflammatory Diseases; Fever; Body Temperature Changes; 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