PharmacokineticsPhase 1NCT00983216
Drug-Drug Interaction Study Between Colchicine and Ketoconazole
A Phase 1 study testing Colchicine and Ketoconazole in people with Pharmacokinetics, run by Mutual Pharmaceutical Company, Inc. at 1 site in United States.
Trial summary
Ketoconazole is a potent inhibitor of the cytochrome P450 (CYP) 3A4 enzyme system, one of the enzyme systems responsible for the metabolism of colchicine. This study will evaluate the effect of multiple doses of ketoconazole on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetics
- What is being tested?
- Colchicine and Ketoconazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2008to Aug 2008
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adults 18-45 years of age, non-smoking and non-pregnant (post-menopausal, 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
Who cannot join
- Recent participation (within 28 days) in other research studies
- Recent significant blood donation or plasma 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, gallbladder or biliary tract, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, 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 28 days prior to the first dose and throughout the study
- Drug allergies to colchicine or ketoconazole or any other anti-fungal agent
Trial locations and contacts
1 site in 1 country.
United States1 site
PRACS Institute, Ltd. - Cetero Research
Fargo, North Dakota, 58104
About this study
Official title: A One-Directional, Open-Label Drug Interaction Study to Investigate the Effects of Multiple-Dose Ketoconazole on Single-Dose Pharmacokinetics of Colchicine in Healthy Volunteers
Ketoconazole is a potent inhibitor of the cytochrome P450 (CYP) 3A4 enzyme system, one of the enzyme systems responsible for the metabolism of colchicine. This study will evaluate the effect of multiple doses of ketoconazole on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. A secondary objective is to evaluate the safety and tolerability of this regimen in healthy volunteers. All study subjects will be monitored for adverse events throughout the study period.
Read the detailed description
Ketoconazole is a potent inhibitor of the cytochrome P450 (CYP) 3A4 enzyme system, one of the enzyme systems responsible for the metabolism of colchicine. This study will evaluate the effect of multiple doses of ketoconazole on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. A secondary objective is to evaluate the safety and tolerability of this regimen in healthy volunteers. All study subjects will be monitored for adverse events throughout the study period. After a fast of at least 10 hours, twenty-four healthy, non-smoking, non-obese, non-pregnant adult volunteers between the ages of 18 and 45 years will be given one dose of colchicine (1 x 0.6 mg tablet) orally on Day 1. Fasting will continue for 4 hours after the dose. Blood samples will be drawn from all participants before dosing and for twenty-four hours post-dose on a confined basis at times sufficient to adequately define the pharmacokinetics of colchicine. Blood sampling will then continue on a non-confined basis on Days 2-5. On Days 15-18, subjects will return to the clinic daily for non-confined dosing of ketoconazole (1 x 200 mg tablet) twice daily, every 12 hours. Administered ketoconazole doses on these days will not necessarily be in a fasted state. On Day 15, after taking the first dose of ketoconazole, subjects will remain in the clinic for observation for 1 hour post-dose administration. Then, on Day 19, co-administration of a single dose of colchicine (1 x 0.6 mg tablet) and ketoconazole (1 x 200 mg tablet) will occur following a fast of at least 10 hours in subjects confined to the clinic for dosing and 24-hour blood sampling will be performed at times sufficient to adequately determine the pharmacokinetics of colchicine. Blood sampling will continue on a non-confined basis on Days 20-23. Fasting will continue for 4 hours following the co-administered dose of ketoconazole and colchicine. The final dose of ketoconazole (1 x 200 mg tablet) will be administered to subjects the evening of Day 19, in a non-fasting state. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. Subjects will be monitored throughout participation in the study for adverse reactions to the study drug and/or procedures. Vital signs (blood pressure and pulse) will be measured prior to dosing and at 1, 2, and 3 hours following drug administration on Days 1 and 19 to coincide with peak plasma concentrations of both colchicine and ketoconazole. 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.
- Conditions
- Pharmacokinetics
- Being tested
- Colchicine, Ketoconazole
- Keywords
- blood levels over time;, pharmacokinetics;, healthy adult;, cytochrome p450
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ColchicineDrug
Also called COLCRYS TM
A single dose of colchicine 0.6 mg administered alone at 7:30 a.m. on Day 1.
KetoconazoleDrug
one 200 mg Ketoconazole tablet administered twice daily at 7:15 a.m. and 7:15 p.m. on Days 15-18 without regard to meals, then along with colchicine at 7:15 a.m. on Day 19 after an overnight fast of at least 10 hours; final dose of 200 mg administered at 7:15 p.m. on Day 19
ColchicineDrug
A single dose of colchicine 0.6 mg administered along with ketoconazole at 7:15 a.m. on Day 19 after an overnight fast of at least 10 hours
| Study group | Role | What they receive |
|---|---|---|
| Colchicine alone | Active comparator | -baseline colchicine pharmacokinetics Receives: Drug: Colchicine |
| Colchicine with Steady-State Ketoconazole | Experimental | -colchicine pharmacokinetics in presence of steady-state ketoconazole Receives: Drug: Ketoconazole; Drug: Colchicine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Plasma Concentration (Cmax)
The maximum or peak concentration that colchicine reaches in the plasma.
Measured: 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
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]
The area under the colchicine plasma concentration versus time curve, from time 0 to the time of the last measurable colchicine concentration (t), as calculated by the linear trapezoidal rule.
Measured: 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
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]
The area under the colchicine 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 colchicine plasma concentration to the elimination rate constant.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2009 (estimated)
- Study startJul 2008
- Primary completionAug 2008
- Study completionAug 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PharmacokineticsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mutual Pharmaceutical Company, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Anthony R Godfrey, Pharm.D., Principal investigator, PRACS - Cetero
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00983216
- Sponsor's protocol ID
- MPC-004-08-1012
- Status last verified
- Oct 2009
- First submitted
- 13 Aug 2009
- Last updated
- 15 Oct 2009
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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. doi: 10.1002/art.30389.
PubMed 21480191
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A One-Directional, Open-Label Drug Interaction Study to Investigate the Effects of Multiple-Dose Ketoconazole on Single-Dose Pharmacokinetics of Colchicine in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT00983216
- Acronym / sponsor ID
- MPC-004-08-1012
- Conditions
- Pharmacokinetics
- Keywords
- blood levels over time;, pharmacokinetics;, healthy adult;, cytochrome p450
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Mutual Pharmaceutical Company, Inc.Industry (pharma, biotech, devices)
- Study start
- Jul 2008
- Primary completion
- Aug 2008 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 24 Sep 2009 (estimated)
- Results
- Posted 24 Sep 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ketoconazole is a potent inhibitor of the cytochrome P450 (CYP) 3A4 enzyme system, one of the enzyme systems responsible for the metabolism of colchicine. This study will evaluate the effect of multiple doses of ketoconazole on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. A secondary objective is to evaluate the safety and tolerability of this regimen in healthy volunteers. All study subjects will be monitored for adverse events throughout the study period.
Detailed description
Ketoconazole is a potent inhibitor of the cytochrome P450 (CYP) 3A4 enzyme system, one of the enzyme systems responsible for the metabolism of colchicine. This study will evaluate the effect of multiple doses of ketoconazole on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. A secondary objective is to evaluate the safety and tolerability of this regimen in healthy volunteers. All study subjects will be monitored for adverse events throughout the study period. After a fast of at least 10 hours, twenty-four healthy, non-smoking, non-obese, non-pregnant adult volunteers between the ages of 18 and 45 years will be given one dose of colchicine (1 x 0.6 mg tablet) orally on Day 1. Fasting will continue for 4 hours after the dose. Blood samples will be drawn from all participants before dosing and for twenty-four hours post-dose on a confined basis at times sufficient to adequately define the pharmacokinetics of colchicine. Blood sampling will then continue on a non-confined basis on Days 2-5. On Days 15-18, subjects will return to the clinic daily for non-confined dosing of ketoconazole (1 x 200 mg tablet) twice daily, every 12 hours. Administered ketoconazole doses on these days will not necessarily be in a fasted state. On Day 15, after taking the first dose of ketoconazole, subjects will remain in the clinic for observation for 1 hour post-dose administration. Then, on Day 19, co-administration of a single dose of colchicine (1 x 0.6 mg tablet) and ketoconazole (1 x 200 mg tablet) will occur following a fast of at least 10 hours in subjects confined to the clinic for dosing and 24-hour blood sampling will be performed at times sufficient to adequately determine the pharmacokinetics of colchicine. Blood sampling will continue on a non-confined basis on Days 20-23. Fasting will continue for 4 hours following the co-administered dose of ketoconazole and colchicine. The final dose of ketoconazole (1 x 200 mg tablet) will be administered to subjects the evening of Day 19, in a non-fasting state. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. Subjects will be monitored throughout participation in the study for adverse reactions to the study drug and/or procedures. Vital signs (blood pressure and pulse) will be measured prior to dosing and at 1, 2, and 3 hours following drug administration on Days 1 and 19 to coincide with peak plasma concentrations of both colchicine and ketoconazole. 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
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Colchicine alone | Active comparator | Drug: Colchicine-baseline colchicine pharmacokinetics |
| Colchicine with Steady-State Ketoconazole | Experimental | Drug: Ketoconazole, Drug: Colchicine-colchicine pharmacokinetics in presence of steady-state ketoconazole |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy adults 18-45 years of age, non-smoking and non-pregnant (post-menopausal, 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
Key exclusion criteria (8 listed)
- Recent participation (within 28 days) in other research studies
- Recent significant blood donation or plasma 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ColchicineAlso: COLCRYS TMA single dose of colchicine 0.6 mg administered alone at 7:30 a.m. on Day 1. | Drug | Colchicine alone |
| Ketoconazoleone 200 mg Ketoconazole tablet administered twice daily at 7:15 a.m. and 7:15 p.m. on Days 15-18 without regard to meals, then along with colchicine at 7:15 a.m. on Day 19 after an overnight fast of at least 10 hours; final dose of 200 mg administered at 7:15 p.m. on Day 19 | Drug | Colchicine with Steady-State Ketoconazole |
| ColchicineA single dose of colchicine 0.6 mg administered along with ketoconazole at 7:15 a.m. on Day 19 after an overnight fast of at least 10 hours | Drug | Colchicine with Steady-State Ketoconazole |
Primary outcome
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
The maximum or peak concentration that colchicine reaches in the plasma.
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
The area under the colchicine plasma concentration versus time curve, from time 0 to the time of the last measurable colchicine concentration (t), as calculated by the linear trapezoidal rule.
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
The area under the colchicine 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 colchicine plasma concentration to the elimination rate constant.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2009.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21480191Terkeltaub 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. doi: 10.1002/art.30389.
- Recalls, Market Withdrawals and Safety AlertsLink provided by the sponsor.
- Daily Med - Posting of Recently Submitted Labeling to the FDALink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anthony R Godfrey, Pharm.D. principal investigator
PRACS - Cetero
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Colchicine and Ketoconazole in people with Pharmacokinetics, run by Mutual Pharmaceutical Company, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Sep 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00983216, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2009.