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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier:
NCT01075906
First received: February 24, 2010
Last updated: January 9, 2012
Last verified: January 2012
  Purpose

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 Intervention Phase
Familial Mediterranean Fever
Drug: colchicine sprinkle capsules
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Mutual Pharmaceutical Company, Inc.:

Primary Outcome Measures:
  • Maximum Plasma Concentration [ Time Frame: 15 days ] [ Designated as safety issue: No ]
    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

  • Area Under the Concentration Time Curve from Time Zero to the Time of Last Measured Concentration (AUC 0-t) [ Time Frame: 15 days ] [ Designated as safety issue: No ]
    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.

  • Area Under the Concentration Time Curve from Zero through Infinity [ Time Frame: 15 days ] [ Designated as safety issue: No ]
    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:
  • Acute Phase Reactant (ESR, CRP, SAA) Levels [ Time Frame: 15 days ] [ Designated as safety issue: No ]
    Pharmacodynamic samples collected pre-dose on Days 7, 1 and 15


Enrollment: 75
Study Start Date: August 2010
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   2 Years to 65 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01075906

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
Hadassah Medical Center
Jerusalem, Israel, 91120
Pediatric Rheumatology Unit - Shaare Zedek Medical Center
Jerusalem, Israel, 91031
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

No publications provided

Responsible Party: Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier: NCT01075906     History of Changes
Other Study ID Numbers: MPC-006-09-1001
Study First Received: February 24, 2010
Last Updated: January 9, 2012
Health Authority: Israel: Ethics Commission
United States: Food and Drug Administration

Keywords provided by Mutual Pharmaceutical Company, Inc.:
pharmacokinetics

Additional relevant MeSH terms:
Fever
Brucellosis
Familial Mediterranean Fever
Hereditary Autoinflammatory Diseases
Body Temperature Changes
Signs and Symptoms
Gram-Negative Bacterial Infections
Bacterial Infections
Genetic Diseases, Inborn
Skin Diseases, Genetic
Skin Diseases
Colchicine
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 30, 2014