Drug-Drug Interaction Study of Colchicine and Theophylline

NCT00983905 | Completed Phase 1 Results

• 1 other identifier: MPC-004-08-1010
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pharmacokinetics

Keywords

healthy;; adult;; blood levels over time

Outcome Measures

Primary Outcomes (3)

• Maximum Plasma Concentration (Cmax)

  The maximum or peak concentration that theophylline drug reaches in the plasma.

  serial pharmacokinetic blood samples drawn within 1 hour prior to theophylline dosing (0 hour) on Days 1 and 19, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after theophylline dose administration

• Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]

  The area under the theophylline plasma concentration versus time curve, from time 0 to the time of the last measurable theophylline concentration (t), as calculated by the linear trapezoidal rule.

  serial pharmacokinetic blood samples drawn within 1 hour prior to theophylline dosing (0 hour) on Days 1 and 19, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after theophylline dose administration

• Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]

  The area under the theophylline 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 theophylline plasma concentration to the elimination rate constant.

  serial pharmacokinetic blood samples drawn within 1 hour prior to theophylline dosing (0 hour) on Days 1 and 19, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after theophylline dose administration

Study Arms (2)

Theophylline alone

ACTIVE COMPARATOR

baseline theophylline kinetics

Drug: Theophylline

Theophylline with steady-state Colchicine

EXPERIMENTAL

theophylline pharmacokinetics upon administration with colchicine at steady-state

Drug: Theophylline; Drug: Colchicine

Interventions

Theophylline DRUG

single doses of 300 mg (80 mg/15 ml elixer) administered alone at 7:45 am on Day 1 and then along with colchicine at 7:45 am on Day 19

Also known as: Elixophyllin® Elixir (Theophylline Anhydrous) 80/15 ml concentrate

Theophylline alone; Theophylline with steady-state Colchicine

Colchicine DRUG

one 0.6 mg tablet twice daily at 7:45 am and 7:45 pm on Days 5 to 19

Theophylline with steady-state Colchicine

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• History or presence of significant cardiovascular, pulmonary, hepatic, gallbladder or biliary tract, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, 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

Sponsors & Collaborators

• Mutual Pharmaceutical Company, Inc.: lead

Study Sites (1)

PRACS Institute, Ltd. - Cetero Research

Fargo, North Dakota, 58104, United States

Location

Related Links

• Recalls, Market Withdrawals and Safety Alerts
• Daily Med - Posting of Recently Submitted Labeling to the FDA

MeSH Terms

Interventions

Theophylline; Colchicine

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Medical Affairs Director
• Organization: Mutual Pharmaceutical Company, Inc.

clinicaltrials@urlmutual.com

215-697-1743

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: August 13, 2009
• First Posted: September 24, 2009
• Study Start: August 1, 2008
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2008
• Last Updated: March 2, 2010
• Results First Posted: September 24, 2009

Record last verified: 2010-02

Locations

US (1)