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Drug-Food Interaction Study of Seville Orange Juice and Colchicine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00960193
Recruitment Status : Completed
First Posted : August 17, 2009
Results First Posted : March 16, 2010
Last Update Posted : June 8, 2011
Sponsor:
Information provided by:
Mutual Pharmaceutical Company, Inc.

Brief Summary:
Seville orange juice is an inhibitor of the intestinal cytochrome P450 (CYP) 3A4 enzyme, one of the enzymes responsible for the metabolism of colchicine. This study will evaluate the effect of multiple daily consumptions of Seville orange juice on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. A secondary objective is to evaluate the safety and tolerability of this regimen in healthy volunteers. All study subjects will be monitored for adverse events throughout the study period.

Condition or disease Intervention/treatment Phase
Healthy Drug: Colchicine Other: Seville Orange Juice Phase 1

Detailed Description:
Seville orange juice is an inhibitor of the intestinal cytochrome P450 (CYP) 3A4 enzyme, one of the enzymes responsible for the metabolism of colchicine. This study will evaluate the effect of multiple daily consumptions of Seville orange juice on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. Twenty-four healthy, non-smoking, non-obese, non-pregnant adult volunteers between the ages of 18 and 45 will be given one dose of colchicine (1 x 0.6 mg tablet) on Day 1, after an overnight fast. Fasting will continue for 4 hours after the dose. Blood samples will be drawn from all participants before dosing and for 24 hours post-dose to adequately define the baseline pharmacokinetics of colchicine. After a 14 day washout period, starting on the morning of Day 15 and continuing through Day 17, subjects will return to the clinic for consumption of an administered 240 ml dose of Seville orange juice in the morning and evening. At 8am on Day 18 after an overnight fast, all subjects will receive a co-administered single oral dose of colchicine (1 x 0.6 mg) and Seville orange juice (1 x 240 ml). Fasting will continue for 4 hours after the dose. Blood samples will be drawn from all participants before dosing and for 24 hours post-dose to adequately define the pharmacokinetics of colchicine in the presence of Seville orange juice. Subjects will consume the final administered 240 ml dose of Seville orange juice in the evening on Day 18. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. Subjects will be monitored throughout participation in the study for adverse reactions to the study drug and/or procedures. Seated blood pressure and pulse will be measured prior to dosing and at approximately 1, 2, and 3 hours following drug administration on Days 1 and 18 to coincide with peak plasma concentrations of colchicine. All adverse events whether elicited by query, spontaneously reported, or observed by clinic staff will be evaluated by the investigator and reported in the subject's case report form.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A One-Directional, Open-Label Drug-Food Interaction Study to Investigate the Effects of Multiple-Daily Consumptions of Seville Orange Juice on the Single-Dose Pharmacokinetics of Colchicine in Healthy Volunteers
Study Start Date : February 2009
Actual Primary Completion Date : April 2009
Actual Study Completion Date : April 2009

Resource links provided by the National Library of Medicine

Drug Information available for: Colchicine

Arm Intervention/treatment
Active Comparator: Colchicine Alone
baseline colchicine pharmacokinetics
Drug: Colchicine
A single dose of 0.6 mg colchicine administered alone in the morning on Day 1 and a single dose of 0.6 mg colchicine administered with Seville orange juice in the morning on Day 18 after an overnight fast of at least 10 hours.

Experimental: Colchicine with Seville Orange Juice
colchicine pharmacokinetics in presence of Seville orange juice
Drug: Colchicine
A single dose of 0.6 mg colchicine administered alone in the morning on Day 1 and a single dose of 0.6 mg colchicine administered with Seville orange juice in the morning on Day 18 after an overnight fast of at least 10 hours.

Other: Seville Orange Juice
240 mL of Seville orange juice administered in the morning and evening on Days 15 to 18.




Primary Outcome Measures :
  1. Maximum Plasma Concentration (Cmax) of Colchicine [ Time Frame: serial pharmacokinetic blood samples drawn immediately prior to colchicine dosing on Days 1 and 18, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours after colchicine dose administration. ]
    The maximum or peak concentration that colchicine reaches in the plasma.

  2. Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] [ Time Frame: Serial pharmacokinetic blood samples drawn immediately prior to colchicine dosing on Days 1 and 18, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours after colchicine dose administration. ]
    The area under the plasma concentration versus time curve, from time 0 to the time of the last measurable colchicine concentration (t), as calculated by the linear trapezoidal rule.

  3. Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] [ Time Frame: Serial pharmacokinetic blood samples drawn immediately prior to colchicine dosing on Days 1 and 18, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours after colchicine dose administration. ]
    The area under the plasma concentration versus time curve from time 0 to infinity. AUC(0-∞) was calculated as the sum of AUC(0-t) plus the ratio of the last measurable colchicine plasma concentration to the elimination rate constant.



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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy adults 18-45 years of age
  • Non-smoking and non-pregnant (post-menopausal, surgically sterile or using effective contraceptive measures)
  • Body mass index (BMI) greater than or equal to 18 and less than or equal to 32, inclusive
  • Hemoglobin greater than or equal to 11.5g/dL

Exclusion Criteria:

  • Recent participation (within 28 days) in other research studies
  • Recent significant blood donation or plasma donation
  • Pregnant or lactating
  • Test positive at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV)
  • Recent (2-year) history or evidence of alcoholism or drug abuse
  • History or presence of significant cardiovascular, pulmonary, hepatic, gallbladder or biliary tract, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease
  • Subjects who have used any drugs or substances known to inhibit or induce cytochrome (CYP) P450 enzymes and/or P-glycoprotein (P-gp) within 28 days prior to the first dose and throughout the study
  • Drug allergies to colchicine
  • Intolerance or food allergy to Seville orange juice

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00960193


Locations
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United States, North Dakota
PRACS Institute, Ltd. - Cetero Research
Fargo, North Dakota, United States, 58104
Sponsors and Collaborators
Mutual Pharmaceutical Company, Inc.
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Vice President, Branded Products and Medical Affairs, Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier: NCT00960193    
Other Study ID Numbers: MPC-004-08-1018
First Posted: August 17, 2009    Key Record Dates
Results First Posted: March 16, 2010
Last Update Posted: June 8, 2011
Last Verified: June 2011
Keywords provided by Mutual Pharmaceutical Company, Inc.:
blood levels over time
colchicine
seville orange juice
pharmacokinetics
Additional relevant MeSH terms:
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Colchicine
Gout Suppressants
Antirheumatic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents