Drug Interaction Study of Colchicine and Theophylline

NCT01601132 | Completed Phase 4 Results

• 2 other identifiers: MPC-004-11-4001U1111-1141-7355
• 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

Healthy

Keywords

pharmacokinetics; colchicine; theophylline

Outcome Measures

Primary Outcomes (6)

• Time to Reach the Maximum Plasma Concentration (Tmax) of Theophylline

  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.

  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.

• Maximum Plasma Concentration (Cmax) of Theophylline

  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.

  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.

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

  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.

  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.

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

  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.

  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.

• Apparent Total Body Clearance (CL/F) of Theophylline

  Apparent total body clearance after oral administration, calculated as Dose /(AUC0-∞).

  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.

• Apparent Total Volume of Distribution (Vd/F) of Theophylline

  Apparent total volume of distribution after oral administration, calculated as Dose /(AUC0-∞) \* Apparent first-order elimination rate constant \[Kel\])

  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.

Study Arms (2)

theophylline

EXPERIMENTAL

300mg (80mg/15ml elixir) theophylline

Drug: theophylline

Colchicine

EXPERIMENTAL

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

Interventions

theophylline DRUG

300mg (80mg/15ml elixir)

Also known as: Elixophyllin®

theophylline

colchicine DRUG

colchicine 0.6mg by mouth twice daily on Days 5-19, co-administered with theophylline 300mg (80mg/15ml) on the morning of Day 19

Also known as: COLCRYS®

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; hemoglobin greater than or equal to 11.5g/dL

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
• 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

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Worlwide Clinical Trials Drug Development Solutions, Clinical Research Services

San Antonio, Texas, 78217, United States

Location

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: Sr. VP, Clinical Science
• Organization: Takeda Global Research and Development Center, Inc.

clinicaltrialregistry@tpna.com

800-778-2860

Study Officials

• Matthew Davis, M.D.

  Mutual Pharmaceutical Company, Inc.

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2012
• First Posted: May 17, 2012
• Study Start: May 1, 2012
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: June 17, 2013
• Results First Posted: June 17, 2013

Record last verified: 2013-04

Locations

US (1)