Drug Interaction Study of Colchicine and Theophylline

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01601132
First received: May 15, 2012
Last updated: April 18, 2013
Last verified: April 2013
  Purpose

Colchicine is a supressor of hepatic CYP1A2 and theophylline is a sensitive CYP1A2 probe substrate. When the two are co-administered the potential exists for a clinically significant drug interaction. This study aims to determine the effect of steady-state colchicine on the pharmacokinetics of theophylline administered as a single dose. A secondary goal is to evaluate the safety and tolerability of this regimen in healthy volunteers. All study subjects will be monitored for adverse events throughout the entire study period.


Condition Intervention Phase
Healthy
Drug: theophylline
Drug: colchicine
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: An Open-Label, One Sequence, Pharmacokinetic Drug Interaction Study of Colchicine and Theophylline in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Time to Reach the Maximum Plasma Concentration (Tmax) of Theophylline [ Time Frame: Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration. ] [ Designated as safety issue: No ]
    The time to each the maximum or peak concentration of theophylline in the plasma, after a single dose on Day 1, and after a single dose on Day 19, following 14 days of colchicine dosing.

  • Maximum Plasma Concentration (Cmax) of Theophylline [ Time Frame: Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration. ] [ Designated as safety issue: No ]
    The maximum or peak concentration of theophylline in the plasma, after a single dose on Day 1, and after another single dose on Day 19 following 14 days of colchicine dosing.

  • Area Under the Concentration Versus Time Curve From Time 0 to Time of the Last Quantifiable Concentration[AUC(0-t)] [ Time Frame: Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration. ] [ Designated as safety issue: No ]
    The area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration (t), as calculated by the linear trapezoidal rule for theophylline.

  • Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] [ Time Frame: Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration. ] [ Designated as safety issue: No ]
    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 plasma concentration to the elimination rate constant for theophylline.

  • Apparent Total Body Clearance (CL/F) of Theophylline [ Time Frame: Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration. ] [ Designated as safety issue: No ]
    Apparent total body clearance after oral administration, calculated as Dose /(AUC0-∞).

  • Apparent Total Volume of Distribution (Vd/F) of Theophylline [ Time Frame: Day 1 and Day 19 blood samples drawn pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after dose administration. ] [ Designated as safety issue: No ]
    Apparent total volume of distribution after oral administration, calculated as Dose /(AUC0-∞) * Apparent first-order elimination rate constant [Kel])


Enrollment: 30
Study Start Date: May 2012
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: theophylline
300mg (80mg/15ml elixir) theophylline
Drug: theophylline
300mg (80mg/15ml elixir)
Other Name: Elixophyllin®
Experimental: Colchicine
colchicine 0.6mg by mouth twice daily on Days 5-19, co-administered with theophylline 300mg (80mg/15ml) on the morning of Day 19
Drug: colchicine
colchicine 0.6mg by mouth twice daily on Days 5-19, co-administered with theophylline 300mg (80mg/15ml) on the morning of Day 19
Other Name: COLCRYS®

Detailed Description:

Colchicine is a supressor of hepatic CYP1A2 and theophylline is a sensitive CYP1A2 probe substrate. When the two are co-administered the potential exists for a clinically significant drug interaction. This study aims to determine the effect of steady-state colchicine on the pharmacokinetics of theophylline administered as a single dose. After a fast of at least 10 hours, thirty healthy, non-smoking, non-obese, non-pregnant adult volunteers between the ages of 18 and 45 will be given one dose of 300mg (80mg/15ml concentrate) theophylline (theophylline elixir) on Day 1. 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 on a confined basis at times sufficient to adequately determine the pharmacokinetics of theophylline. Blood sampling will then continue on a non-confined basis on days 2-3. A four day washout period will be completed after the theophylline dose on Day 1 and prior to administration of the first colchicine dose on Day 5. Participants will return to the clinic on days 5-18 for non-confined dosing of colchicine (1x0.6mg twice daily every 12 hours). Administered dosing on these days will not necessarily be in a fasted state. Co-administration of a single 300mg dose of theophylline (80mg/15ml) and colchicine (1x0.6mg) will occur on the morning of Day 19 following a fast of at least 10 hours. Twelve hours later, subjects will receive the last dose of colchicine (1x0.6mg). Blood samples will be drawn from all participants before dosing on Day 19 and for 24 hours post-dose on a confined basis at times sufficient to adequately determine the pharmacokinetics of theophylline. Blood sampling will then continue on a non-confined basis on days 20 and 21. 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, 5 (after the morning dose) and 19. 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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy adults 18-45 years of age, non smoking and non-pregnant (postmenopausal, surgically sterile or using effective contraceptive measures) with a 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 donation of plasma
  • 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
  • Subjects who test positive for drugs of abuse or alcohol at screening or check-in
  • History or presence of significant cardiovascular, pulmonary, hepatic, gallbladder or biliary tract, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease or active sexually transmitted disease
  • History of neuropathy or muscle disorders, peptic ulcer disease, clinically significant cardiac arrhythmias, seizure disorder, and low white blood cell count or other bone marrow disorders
  • 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
  • History of allergy or sensitivity to colchicine or theophylline or aminophylline
  • Subjects who have had a tattoo or body piercing within 30 days prior to administration of study drug
  • Subjects with irritable bowel syndrome, chronic diarrhea or other chronic gastro-intestinal problems
  • Subjects who are lactose intolerant
  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: NCT01601132

Locations
United States, Texas
Worlwide Clinical Trials Drug Development Solutions, Clinical Research Services
San Antonio, Texas, United States, 78217
Sponsors and Collaborators
Takeda
Investigators
Study Chair: Matthew Davis, M.D. Mutual Pharmaceutical Company, Inc.
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01601132     History of Changes
Other Study ID Numbers: MPC-004-11-4001, U1111-1141-7355
Study First Received: May 15, 2012
Results First Received: March 7, 2013
Last Updated: April 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
pharmacokinetics
colchicine
theophylline

Additional relevant MeSH terms:
Colchicine
Theophylline
Anti-Asthmatic Agents
Antimitotic Agents
Antineoplastic Agents
Antirheumatic Agents
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Enzyme Inhibitors
Gout Suppressants
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Phosphodiesterase Inhibitors
Physiological Effects of Drugs
Purinergic Agents
Purinergic Antagonists
Purinergic P1 Receptor Antagonists
Respiratory System Agents
Therapeutic Uses
Tubulin Modulators
Vasodilator Agents

ClinicalTrials.gov processed this record on October 23, 2014