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.

Tracking Information

• First Submitted Date: February 24, 2010
• First Posted Date: February 25, 2010
• Last Update Posted Date: January 10, 2012
• Study Start Date: August 2010
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 24, 2010)

• 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
• 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.
• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 24, 2010)

Acute Phase Reactant (ESR, CRP, SAA) Levels [ Time Frame: 15 days ]

Pharmacodynamic samples collected pre-dose on Days 7, 1 and 15

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Familial Mediterranean Fever

Intervention

Drug: colchicine sprinkle capsules

0.3 mg

Study Arms

• Experimental: Colchicine
  Colchicine Sprinkle Capsules, 0.3 mg - dose administered according to age range on Day 1
  Intervention: Drug: colchicine sprinkle capsules
• 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
  Intervention: Drug: colchicine sprinkle capsules

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 24, 2010): 75
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 2011
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 65 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Armenia, Israel, Turkey, United States

Administrative Information

• NCT Number: NCT01075906
• Other Study ID Numbers: MPC-006-09-1001
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Mutual Pharmaceutical Company, Inc.
• Study Sponsor: Mutual Pharmaceutical Company, Inc.
• Collaborators: Not Provided

Investigators

• Study Chair: Matthew Davis, MD; Mutual Pharmaceutical Company, Inc.

• PRS Account: Mutual Pharmaceutical Company, Inc.
• Verification Date: January 2012