Drug-Drug Interaction Study of Colchicine and Clarithromycin - 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: clarithromycin

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, adult male and female volunteers, consisting of members of the community at large, were enrolled.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
56 subjects screened, 32 were screen failures

Reporting Groups

	Description
Colchicine Alone / With Clarithromycin	[All subjects received each of the study treatments.] Each subject received one colchicine 0.6 mg tablet on Day 1 at 9:00 a.m. after an overnight fast of at least 10 hours, followed by a 21 day washout period. On Day 22, subjects began taking one 250 mg clarithromycin tablet every 12 hours at 8:00 a.m. and 8:00 p.m. for 7 days without regard to meals. Then, on Day 29, each subject received one colchicine 0.6 mg tablet along with final dose of 250 mg clarithromycin at 9:00 a.m. after an overnight fast of at least 10 hours.

Description

Colchicine Alone / With Clarithromycin

[All subjects received each of the study treatments.] Each subject received one colchicine 0.6 mg tablet on Day 1 at 9:00 a.m. after an overnight fast of at least 10 hours, followed by a 21 day washout period. On Day 22, subjects began taking one 250 mg clarithromycin tablet every 12 hours at 8:00 a.m. and 8:00 p.m. for 7 days without regard to meals. Then, on Day 29, each subject received one colchicine 0.6 mg tablet along with final dose of 250 mg clarithromycin at 9:00 a.m. after an overnight fast of at least 10 hours.

Participant Flow for 4 periods

Period 1: Colchicine Alone

	Colchicine Alone / With Clarithromycin
STARTED	24
COMPLETED	24
NOT COMPLETED	0

Period 2: 21 Day Washout Period

	Colchicine Alone / With Clarithromycin
STARTED	24
COMPLETED	24
NOT COMPLETED	0

Period 3: Clarithromycin Alone

	Colchicine Alone / With Clarithromycin
STARTED	24
COMPLETED	23 ^[1]
NOT COMPLETED	1
Protocol Violation	1

[1]	One subject was dropped due to noncompliance with outpatient clarithromycin regimen.

Period 4: Colchicine With Clarithromycin

	Colchicine Alone / With Clarithromycin
STARTED	23
COMPLETED	23
NOT COMPLETED	0

Baseline Characteristics

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Reporting Groups

	Description
Colchicine Alone / With Clarithromycin	[All subjects received each of the study treatments.] Each subject received one colchicine 0.6 mg tablet on Day 1 at 9:00 a.m. after an overnight fast of at least 10 hours, followed by a 21 day washout period. On Day 22, subjects began taking one 250 mg clarithromycin tablet every 12 hours at 8:00 a.m. and 8:00 p.m. for 7 days without regard to meals. Then, on Day 29, each subject received one colchicine 0.6 mg tablet along with final dose of 250 mg clarithromycin at 9:00 a.m. after an overnight fast of at least 10 hours.

Description

Colchicine Alone / With Clarithromycin

[All subjects received each of the study treatments.] Each subject received one colchicine 0.6 mg tablet on Day 1 at 9:00 a.m. after an overnight fast of at least 10 hours, followed by a 21 day washout period. On Day 22, subjects began taking one 250 mg clarithromycin tablet every 12 hours at 8:00 a.m. and 8:00 p.m. for 7 days without regard to meals. Then, on Day 29, each subject received one colchicine 0.6 mg tablet along with final dose of 250 mg clarithromycin at 9:00 a.m. after an overnight fast of at least 10 hours.

Baseline Measures

	Colchicine Alone / With Clarithromycin
Number of Participants [units: participants]	24
Age ^[1] [units: participants]
<=18 years	0
Between 18 and 65 years	24
>=65 years	0
Age [units: years] Mean ± Standard Deviation	22.3 ± 4.1
Gender [units: participants]
Female	13
Male	11
Race/Ethnicity, Customized [units: participants]
Caucasian	24
Region of Enrollment [units: participants]
United States	24

[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 collected immediately prior to dosing on Days 1 and 29, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours after 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 collected immediately prior to dosing on Days 1 and 29, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours after 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 collected immediately prior to dosing on Days 1 and 29, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours after 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:	NCT00984061 History of Changes
Other Study ID Numbers:	MPC-004-07-1006
Study First Received:	August 13, 2009
Results First Received:	August 13, 2009
Last Updated:	October 5, 2009
Health Authority:	United States: Food and Drug Administration