Drug-Drug Interaction Study Between Colchicine and Ketoconazole - 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: Colchicine Drug: Ketoconazole

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Twenty-four (24) healthy, non-smoking, male and female volunteers, consisting of volunteers from the community at large, were enrolled in the study.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
55 subjects were screened, 12 were screen failures, 7 had schedule conflicts, 1 was not used due to history of non-compliance, and 12 were not needed

Reporting Groups

	Description
Colchicine Alone / With Ketoconazole (at Steady-state)	[All subjects received each of the study treatments.] Each subject received one 0.6 mg colchicine tablet on Day 1 at 7:15 a.m. after an overnight fast, followed by a washout period of 14 days. On Day 15, subjects began taking one 200 mg ketoconazole tablet twice daily at 7:15 a.m. and at 7:15 p.m. without regard to meals. Then, on Day 19, each subject received both one 0.6 mg colchicine tablet and one ketoconazole 200 mg tablet at 7:15 a.m. after an overnight fast. A final dose of ketoconazole was administered at 7:15 p.m. that evening.

Description

Colchicine Alone / With Ketoconazole (at Steady-state)

[All subjects received each of the study treatments.] Each subject received one 0.6 mg colchicine tablet on Day 1 at 7:15 a.m. after an overnight fast, followed by a washout period of 14 days. On Day 15, subjects began taking one 200 mg ketoconazole tablet twice daily at 7:15 a.m. and at 7:15 p.m. without regard to meals. Then, on Day 19, each subject received both one 0.6 mg colchicine tablet and one ketoconazole 200 mg tablet at 7:15 a.m. after an overnight fast. A final dose of ketoconazole was administered at 7:15 p.m. that evening.

Participant Flow for 4 periods

Period 1: Colchicine Alone

	Colchicine Alone / With Ketoconazole (at Steady-state)
STARTED	24
COMPLETED	24
NOT COMPLETED	0

Period 2: 14 Day Washout Period

	Colchicine Alone / With Ketoconazole (at Steady-state)
STARTED	24
COMPLETED	24
NOT COMPLETED	0

Period 3: Ketoconazole Alone

	Colchicine Alone / With Ketoconazole (at Steady-state)
STARTED	24
COMPLETED	24
NOT COMPLETED	0

Period 4: Colchicine With Ketoconazole

	Colchicine Alone / With Ketoconazole (at Steady-state)
STARTED	24
COMPLETED	24
NOT COMPLETED	0

Baseline Characteristics

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Reporting Groups

	Description
Colchicine Alone / With Ketoconazole (at Steady-state)	[All subjects received each of the study treatments.] Each subject received one 0.6 mg colchicine tablet on Day 1 at 7:15 a.m. after an overnight fast, followed by a washout period of 14 days. On Day 15, subjects began taking one 200 mg ketoconazole tablet twice daily at 7:15 a.m. and at 7:15 p.m. without regard to meals. Then, on Day 19, each subject received both one 0.6 mg colchicine tablet and one ketoconazole 200 mg tablet at 7:15 a.m. after an overnight fast. A final dose of ketoconazole was administered at 7:15 p.m. that evening.

Description

Colchicine Alone / With Ketoconazole (at Steady-state)

[All subjects received each of the study treatments.] Each subject received one 0.6 mg colchicine tablet on Day 1 at 7:15 a.m. after an overnight fast, followed by a washout period of 14 days. On Day 15, subjects began taking one 200 mg ketoconazole tablet twice daily at 7:15 a.m. and at 7:15 p.m. without regard to meals. Then, on Day 19, each subject received both one 0.6 mg colchicine tablet and one ketoconazole 200 mg tablet at 7:15 a.m. after an overnight fast. A final dose of ketoconazole was administered at 7:15 p.m. that evening.

Baseline Measures

	Colchicine Alone / With Ketoconazole (at Steady-state)
Number of Participants [units: participants]	24
Age ^[1] [units: participants]
<=18 years	2
Between 18 and 65 years	22
>=65 years	0
Age [units: years] Mean ± Standard Deviation	24.4 ± 5.7
Gender [units: participants]
Female	17
Male	7
Race (NIH/OMB) [units: participants]
American Indian or Alaska Native	0
Asian	0
Native Hawaiian or Other Pacific Islander	0
Black or African American	1
White	23
More than one race	0
Unknown or Not Reported	0
Ethnicity (NIH/OMB) [units: participants]
Hispanic or Latino	0
Not Hispanic or Latino	24
Unknown or Not Reported	0
Region of Enrollment [units: participants]
United States	24

[1]	age range: ≥18 and ≤45 years

Outcome Measures

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1. Primary:

Maximum Plasma Concentration (Cmax) [ Time Frame: serial pharmacokinetic blood samples drawn within 1 hour prior to colchicine dosing (0 hour) on Days 1 and 19, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours after colchicine 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 colchicine dosing (0 hour) on Days 1 and 19, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours after colchicine 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 colchicine dosing (0 hour) on Days 1 and 19, and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours after colchicine dose administration ]

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

No publications provided by Mutual Pharmaceutical Company, Inc.

Publications automatically indexed to this study:

Terkeltaub RA, Furst DE, Digiacinto JL, Kook KA, Davis MW. Novel evidence-based colchicine dose-reduction algorithm to predict and prevent colchicine toxicity in the presence of cytochrome P450 3A4/P-glycoprotein inhibitors. Arthritis Rheum. 2011 Aug;63(8):2226-37.

Responsible Party:	Vice President, Branded Products and Medical Affairs, Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier:	NCT00983216 History of Changes
Other Study ID Numbers:	MPC-004-08-1012
Study First Received:	August 13, 2009
Results First Received:	August 13, 2009
Last Updated:	October 12, 2009
Health Authority:	United States: Food and Drug Administration