Pharmacokinetic Study of an Acute Gout Regimen

• Sponsor: Mutual Pharmaceutical Company, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01017042
• Collaborator: (none)
• Enrollment: 13
• Location: 1
• Arm: 1
• Duration (Days): 30
• Patients Per Site Per Month: 13.2

Study Details

Study Description

Brief Summary

This study aims to characterize the pharmacokinetic profile of colchicine after a regimen of 1.8 mg over two hours. A secondary goal is to evaluate the safety and tolerability of this regimen in healthy volunteers. To this end, all study subjects will be monitored for adverse effects throughout the entire study period.

Condition or Disease	Intervention/Treatment	Phase
Pharmacokinetics	Drug: colchicine tablets	Phase 1

Detailed Description

This study aims to characterize the pharmacokinetic profile of colchicine and its three main metabolites, after a regimen of 1.8 mg over two hours. After a fast of at least 10 hours, fifteen healthy non-smoking, non-obese, non-pregnant adult volunteers between the ages of 18 and 55 will be given colchicine 1.2 mg (2 x 0.6 mg) orally followed by an additional single 0.6mg dose one hour later. Fasting will continue for 4 hours after the first dose at which time a standardized meal will be served. Blood will be drawn from all participants at times sufficient to adequately define the pharmacokinetics of colchicine and its 3 major metabolites, 2, 3 and 10 demethylcolchicine. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. To this end, subjects will be monitored throughout participation in the study for adverse reactions to the study drug and/or procedures. Seated and standing blood pressure and pulse will be measured prior to the first dose and 0.5, 1, 2, 4, and 12 hours post-dose. Twelve-lead electrocardiograms will be obtained at the same time points. All adverse events whether elicited by query, spontaneously reported, or observed by clinic staff will be evaluated by the Investigator and reported in the subject's case report form.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Open-Label Pharmacokinetic Study of a Low-Dose Acute Gout Regimen
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Sep 1, 2007
• Actual Study Completion Date: Oct 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: colchicine colchicine 1.2mg by mouth initially then an additional 0.6mg orally 1 hour later (1.8mg over 2 hours)	Drug: colchicine tablets; colchicine 1.2mg initially; then an additional 0.6mg orally 1 hour later (1.8mg over 2 hours); Other Names: COLCRYS TM

Outcome Measures

Primary Outcome Measures

1. Maximum Plasma Concentration [Pharmacokinetic samples collected pre-dose and 0.5, 1 hour (prior to the second dose), and 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours post-dose (relative to the first dose) and 72 and 96 hours post-dose (on an outpatient basis).]

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

2. Area Under the Concentration Time Curve From Time Zero to the Time of Last Measured Concentration (96 Hours) (AUC 0-t) [Pharmacokinetic samples collected pre-dose and 0.5, 1 hour (prior to the second dose), and 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours post-dose (relative to the first dose) and 72 and 96 hours post-dose (on an outpatient basis).]

   The area under the plasma concentration versus time curve beginning from the first dose until the last quantifiable concentration (96hours), calculated by the linear trapezoidal rule.

3. Area Under The Concentration Time Curve From Zero Through Infinity (AUC∞) [Pharmacokinetic samples collected pre-dose and 0.5, 1 hour (prior to the second dose), and 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours post-dose (relative to the first dose) and 72 and 96 hours post-dose (on an outpatient basis).]

   The area under the plasma concentration versus time curve extrapolated to infinity. AUC∞ is calculated as the sum of Total AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant

Secondary Outcome Measures

1. Electrocardiogram Corrected QT Interval (QTcF) [Measured at baseline, 0.5, 1, 2, and 4 hours]

   Corrected QT interval by Fridericia's formula -Measured at baseline, 0.5, 1, 2, and 4 hours

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy adults 18-55 years of age, non smoking and non-pregnant (postmenopausal, surgically sterile or using effective contraceptive measures) weighing at least 55kg and within 15% of ideal body weight.

Exclusion Criteria:

• Recent participation (within 30 days) in other research studies

• Recent significant blood donation

• 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, renal, haematological, 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 30 days prior to the first dose and throughout the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PRACS Institute, Ltd. - Cetero Research	Fargo	North Dakota	United States	58104

Sponsors and Collaborators

• Mutual Pharmaceutical Company, Inc.

Investigators

• Principal Investigator: Anthony R Godfrey, Pharm.D., PRACS Institiute, Ltd.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT01017042
• Other Study ID Numbers: MPC-004-07-1003
• First Posted: Nov 20, 2009
• Last Update Posted: Nov 20, 2009
• Last Verified: Oct 1, 2009

• Keywords provided by , ,: healthy; blood levels
• Additional relevant MeSH terms: Colchicine

Study Results

Participant Flow

Arm/Group Title	Oral Colchicine 1.2mg + 0.6mg
Arm/Group Description	On the morning of day one after a fast of at least 10 hours, all study participants received colchicine 1.2mg by mouth initially then an additional 0.6mg orally 1 hour later (1.8mg over 2 hours) Blood was drawn at times sufficient to characterize the pharmacokinetics of Colchicine under this therapeutic regimen.
Period Title: Overall Study
STARTED	13
COMPLETED	13
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Oral Colchicine 1.2mg + 0.6mg
Arm/Group Description	On the morning of day one after a fast of at least 10 hours, all study participants received colchicine 1.2mg by mouth initially then an additional 0.6mg orally 1 hour later (1.8mg over 2 hours) Blood was drawn at times sufficient to characterize the pharmacokinetics of Colchicine under this therapeutic regimen.
Overall Participants	13
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	13 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.9 (8.4)
Sex: Female, Male (Count of Participants)
Female	7 53.8%
Male	6 46.2%
Region of Enrollment (participants) [Number]
United States	13 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Plasma Concentration
Description	The maximum or peak concentration that the drug reaches in the plasma.
Time Frame	Pharmacokinetic samples collected pre-dose and 0.5, 1 hour (prior to the second dose), and 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours post-dose (relative to the first dose) and 72 and 96 hours post-dose (on an outpatient basis).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Colchicine 1.2mg + 0.6mg
Arm/Group Description	On the morning of day one after a fast of at least 10 hours, all study participants received colchicine 1.2mg by mouth initially then an additional 0.6mg orally 1 hour later (1.8mg over 2 hours) Blood was drawn at times sufficient to characterize the pharmacokinetics of Colchicine under this therapeutic regimen.
Measure Participants	13
Mean (Standard Deviation) [picograms/ml]	6192.77 (2433.7)

2. Secondary Outcome

Title	Electrocardiogram Corrected QT Interval (QTcF)
Description	Corrected QT interval by Fridericia's formula -Measured at baseline, 0.5, 1, 2, and 4 hours
Time Frame	Measured at baseline, 0.5, 1, 2, and 4 hours

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	Corrected QTc Interval (Baseline)	Corrected QTc Interval (0.5 Hour)	Corrected QTc Interval (1 Hour)	Corrected QTc Interval (2 Hour)	Corrected QTc Interval (4 Hour)
Arm/Group Description	colchicine 1.2mg by mouth initially then an additional 0.6mg orally 1 hour later (1.8mg over 2 hours) QTc corrected by Fridericia's formula (Baseline)	colchicine 1.2mg by mouth initially then an additional 0.6mg orally 1 hour later (1.8mg over 2 hours) QTc corrected by Fridericia's formula (0.5hour)	colchicine 1.2mg by mouth initially then an additional 0.6mg orally 1 hour later (1.8mg over 2 hours) QTc corrected by Fridericia's formula (1 hour)	colchicine 1.2mg by mouth initially then an additional 0.6mg orally 1 hour later (1.8mg over 2 hours) QTc corrected by Fridericia's formula (2 hour)	colchicine 1.2mg by mouth initially then an additional 0.6mg orally 1 hour later (1.8mg over 2 hours) QTc corrected by Fridericia's formula (4 hour)
Measure Participants	13	13	13	13	13
Mean (Standard Deviation) [Milliseconds]	402.28 (19.66)	397.38 (18.37)	399.26 (20.59)	401.51 (20.64)	402.38 (23.16)

3. Primary Outcome

Title	Area Under the Concentration Time Curve From Time Zero to the Time of Last Measured Concentration (96 Hours) (AUC 0-t)
Description	The area under the plasma concentration versus time curve beginning from the first dose until the last quantifiable concentration (96hours), calculated by the linear trapezoidal rule.
Time Frame	Pharmacokinetic samples collected pre-dose and 0.5, 1 hour (prior to the second dose), and 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours post-dose (relative to the first dose) and 72 and 96 hours post-dose (on an outpatient basis).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Colchicine 1.2mg + 0.6mg
Arm/Group Description	On the morning of day one after a fast of at least 10 hours, all study participants received colchicine 1.2mg by mouth initially then an additional 0.6mg orally 1 hour later (1.8mg over 2 hours) Blood was drawn at times sufficient to characterize the pharmacokinetics of Colchicine under this therapeutic regimen.
Measure Participants	13
Mean (Standard Deviation) [pg-hr/ml]	43787.55 (11437.48)

4. Primary Outcome

Title	Area Under The Concentration Time Curve From Zero Through Infinity (AUC∞)
Description	The area under the plasma concentration versus time curve extrapolated to infinity. AUC∞ is calculated as the sum of Total AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant
Time Frame	Pharmacokinetic samples collected pre-dose and 0.5, 1 hour (prior to the second dose), and 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours post-dose (relative to the first dose) and 72 and 96 hours post-dose (on an outpatient basis).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Colchicine 1.2mg + 0.6mg
Arm/Group Description	On the morning of day one after a fast of at least 10 hours, all study participants received colchicine 1.2mg by mouth initially then an additional 0.6mg orally 1 hour later (1.8mg over 2 hours) Blood was drawn at times sufficient to characterize the pharmacokinetics of Colchicine under this therapeutic regimen.
Measure Participants	13
Mean (Standard Deviation) [pg-hr/ml]	52070.06 (13689.27)

Adverse Events

Arm/Group Title	Oral Colchicine 1.2mg + 0.6mg
Arm/Group Description	On the morning of day one after a fast of at least 10 hours, all study participants received colchicine 1.2mg by mouth initially then an additional 0.6mg orally 1 hour later (1.8mg over 2 hours) Blood was drawn at times sufficient to characterize the pharmacokinetics of Colchicine under this therapeutic regimen.
All Cause Mortality
	Oral Colchicine 1.2mg + 0.6mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Oral Colchicine 1.2mg + 0.6mg
	Affected / at Risk (%)	# Events
Total	0/13 (0%)
Other (Not Including Serious) Adverse Events
	Oral Colchicine 1.2mg + 0.6mg
	Affected / at Risk (%)	# Events
Total	5/ (NaN)
Gastrointestinal disorders
Abdominal Pain , Upper	1/13 (7.7%)	1
Diarrhea	2/13 (15.4%)	2
Dyspepsia	1/13 (7.7%)	1
Nausea	1/13 (7.7%)	1
Nervous system disorders
Headache	2/13 (15.4%)	2
Vascular disorders
Hot Flush	1/13 (7.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.