Drug-Drug Interaction Study of Colchicine and Theophylline - Study Results

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Endpoint Classification: Pharmacokinetics Study; Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Basic Science
Condition:	Pharmacokinetics
Interventions:	Drug: Theophylline Drug: Colchicine

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Thirty (30) healthy, non-smoking, male and female volunteers, consisting of members of the community at large, were to be enrolled.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
44 subjects screened, 6 were screen failures, 8 had schedule conflicts

Reporting Groups

	Description
Theophylline Alone / With Colchicine (at Steady State)	[All subjects received each of the study treatments.] Each subject received a single 300 mg dose of theophylline elixer (80 mg/15 ml concentrate) on Day 1 at 7:45am after an overnight fast of at least 10 hours, followed by a washout period of 4 days. On Days 5 to 18, each subject received one 0.6 mg colchicine tablet twice daily at 7:45am and 7:45pm without regard to meals. Then, on Day 19, each subject received both a single dose of theophylline elixer (80 mg/15 ml concentrate) and one 0.6 mg colchicine tablet at 7:45am after an overnight fast of at least 10 hours. (They also received the final dose of one 0.6 mg colchicine tablet at 7:45 pm.)

Description

Theophylline Alone / With Colchicine (at Steady State)

[All subjects received each of the study treatments.] Each subject received a single 300 mg dose of theophylline elixer (80 mg/15 ml concentrate) on Day 1 at 7:45am after an overnight fast of at least 10 hours, followed by a washout period of 4 days. On Days 5 to 18, each subject received one 0.6 mg colchicine tablet twice daily at 7:45am and 7:45pm without regard to meals. Then, on Day 19, each subject received both a single dose of theophylline elixer (80 mg/15 ml concentrate) and one 0.6 mg colchicine tablet at 7:45am after an overnight fast of at least 10 hours. (They also received the final dose of one 0.6 mg colchicine tablet at 7:45 pm.)

Participant Flow for 4 periods

Period 1: Theophylline Alone

	Theophylline Alone / With Colchicine (at Steady State)
STARTED	30
COMPLETED	29 ^[1]
NOT COMPLETED	1
Adverse Event	1

[1]	withdrawn by sponsor due to vomiting(1)

Period 2: 4 Day Washout Period

	Theophylline Alone / With Colchicine (at Steady State)
STARTED	29
COMPLETED	29
NOT COMPLETED	0

Period 3: Colchicine Alone

	Theophylline Alone / With Colchicine (at Steady State)
STARTED	29
COMPLETED	27 ^[1]
NOT COMPLETED	2
Adverse Event	2

[1]	withdrawn by sponsor due to: diarrhea(1); vomiting and diarrhea(1)

Period 4: Theophylline With Colchicine

	Theophylline Alone / With Colchicine (at Steady State)
STARTED	27
COMPLETED	27
NOT COMPLETED	0

Baseline Characteristics

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Reporting Groups

	Description
Theophylline Alone / With Colchicine (at Steady State)	[All subjects received each of the study treatments.] Each subject received a single 300 mg dose of theophylline elixer (80 mg/15 ml concentrate) on Day 1 at 7:45am after an overnight fast of at least 10 hours, followed by a washout period of 4 days. On Days 5 to 18, each subject received one 0.6 mg colchicine tablet twice daily at 7:45am and 7:45pm without regard to meals. Then, on Day 19, each subject received both a single dose of theophylline elixer (80 mg/15 ml concentrate) and one 0.6 mg colchicine tablet at 7:45am after an overnight fast of at least 10 hours. (They also received the final dose of one 0.6 mg colchicine tablet at 7:45 pm.)

Description

Theophylline Alone / With Colchicine (at Steady State)

[All subjects received each of the study treatments.] Each subject received a single 300 mg dose of theophylline elixer (80 mg/15 ml concentrate) on Day 1 at 7:45am after an overnight fast of at least 10 hours, followed by a washout period of 4 days. On Days 5 to 18, each subject received one 0.6 mg colchicine tablet twice daily at 7:45am and 7:45pm without regard to meals. Then, on Day 19, each subject received both a single dose of theophylline elixer (80 mg/15 ml concentrate) and one 0.6 mg colchicine tablet at 7:45am after an overnight fast of at least 10 hours. (They also received the final dose of one 0.6 mg colchicine tablet at 7:45 pm.)

Baseline Measures

	Theophylline Alone / With Colchicine (at Steady State)
Number of Participants [units: participants]	30
Age ^[1] [units: participants]
<=18 years	2
Between 18 and 65 years	28
>=65 years	0
Age [units: years] Mean ± Standard Deviation	25.1 ± 5.9
Gender [units: participants]
Female	14
Male	16
Race (NIH/OMB) [units: participants]
American Indian or Alaska Native	0
Asian	0
Native Hawaiian or Other Pacific Islander	0
Black or African American	2
White	27
More than one race	1
Unknown or Not Reported	0
Region of Enrollment [units: participants]
United States	30

[1]	age range: >=18 and <=45 years old

Outcome Measures

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1. Primary:

Maximum Plasma Concentration (Cmax) [ Time Frame: 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 ]

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2. Primary:

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

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3. Primary:

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

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Measure Type	Primary
Measure Title	Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]
Measure Description	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.
Time Frame	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Theophylline Alone	On Day 1, each subject received a single 300 mg dose of theophylline elixer (80 mg/15 ml concentrate) at 7:45 am after an overnight fast of at least 10 hours, followed by a washout period of 4 days.
Theophylline With Colchicine (at Steady-state)	On Days 5 to 18, each subject received one 0.6 mg colchicine tablet twice daily at 7:45 am and 7:45 pm without regard to meals. Then, on Day 19, each subject received both a single dose of theophylline elixer (80 mg/15 ml concentrate) and one 0.6 mg colchicine tablet at 7:45am after an overnight fast of at least 10 hours. (They also received the final dose of one 0.6 mg colchicine tablet at 7:45 pm.)

Description

Theophylline Alone

On Day 1, each subject received a single 300 mg dose of theophylline elixer (80 mg/15 ml concentrate) at 7:45 am after an overnight fast of at least 10 hours, followed by a washout period of 4 days.

Theophylline With Colchicine (at Steady-state)

On Days 5 to 18, each subject received one 0.6 mg colchicine tablet twice daily at 7:45 am and 7:45 pm without regard to meals. Then, on Day 19, each subject received both a single dose of theophylline elixer (80 mg/15 ml concentrate) and one 0.6 mg colchicine tablet at 7:45am after an overnight fast of at least 10 hours. (They also received the final dose of one 0.6 mg colchicine tablet at 7:45 pm.)

Measured Values

	Theophylline Alone	Theophylline With Colchicine (at Steady-state)
Number of Participants Analyzed [units: participants]	27	27
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] [units: µg-hr/mL] Mean ± Standard Deviation	127.47 ± 42.28	129.39 ± 44.83

No statistical analysis provided for Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Medical Affairs Director
Organization: Mutual Pharmaceutical Company, Inc.
phone: 215-697-1743
e-mail: clinicaltrials@urlmutual.com

No publications provided

Responsible Party:	Vice President, Branded Products and Medical Affairs, Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier:	NCT00983905 History of Changes
Other Study ID Numbers:	MPC-004-08-1010
Study First Received:	August 13, 2009
Results First Received:	August 13, 2009
Last Updated:	February 23, 2010
Health Authority:	United States: Food and Drug Administration