A Phase 1 interventional study of Colchicine and Ritonavir in Pharmacokinetics, sponsored by Mutual Pharmaceutical Company, Inc.. Completed at 1 site in United States. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2009-10-15.
Sponsored by Mutual Pharmaceutical Company, Inc. · Phase 1, Interventional, and Basic science
Ritonavir is a potent inhibitor of CYP3A4, one of the enzymes responsible for the metabolism of colchicine. This study will evaluate the effect of multiple doses of ritonavir 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.
Ritonavir is a potent inhibitor of CYP3A4, one of the enzymes responsible for the metabolism of colchicine. This study will evaluate the effect of multiple doses of ritonavir 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 will be given a single oral dose of colchicine (1 x 0.6 mg tablet) 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. After a 14 day washout period, on study Days 15-18, subjects will return to the clinic daily for non-confined dosing of ritonavir (1 x 100 mg capsule) every 12 hours. Administered ritonavir doses on these days will not necessarily be in a fasted state. On Day 15, after taking the first dose of ritonavir, subjects will remain in the clinic for observation for 1 hour post-dose administration. On day 19 after a fast of at least 10 hours, a single dose of colchicine (1 x 0.6 mg tablet) and ritonavir (1 x 100 mg capsule) will be co-administered to all study participants. Fasting will continue for 4 hours following the co-administered doses of ritonavir and colchicine. All participants will be confined to the clinic for dosing and 24-hour blood sampling at times sufficient to adequately determine the pharmacokinetics of colchicine. Blood sampling will continue on a non-confined basis on Days 20-23. The final dose of ritonavir (1 x 100 mg capsule) 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, 15 and 19 to coincide with peak plasma concentrations of both colchicine and ritonavir. 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.
Mutual Pharmaceutical Company, Inc. is the lead sponsor of 44 studies on the registry; none are open to participants now.
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Exclusion Criteria:
-baseline colchicine pharmacokinetics
Drug: Colchicine
-colchicine pharmacokinetics in presence of steady-state ritonavir
Drug: Ritonavir · Drug: Colchicine
A single dose of colchicine 0.6 mg administered alone at 7:00 a.m. on Day 1 after an overnight fast of at least 10 hours.
Also known as: COLCRYS™
One 100 mg ritonavir capsule administered twice daily at 7:00 a.m. and 7:00 p.m. on Days 15 to 18 without regard to meals, then along with colchicine at 7:00 a.m. on Day 19 after an overnight fast of at least 10 hours; final dose of 100 mg ritonavir administered at 7:00 p.m. on Day 19
Also known as: Norvir® Capsules USP, 100 mg (Abbott Laboratories)
A single dose of colchicine 0.6 mg administered along with ritonavir at 7:00 a.m. on Day 19
Maximum Plasma Concentration (Cmax)
The maximum or peak concentration that colchicine reaches in the plasma.
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
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]
The area under the 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.
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
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]
The area under the 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.
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
Twenty-four (24) healthy, non-smoking, male and female volunteers, consisting of members from the community at large, were enrolled in the study.
| Milestone | Colchicine Alone / With Ritonavir (at Steady-state) |
|---|---|
| Started | 24 |
| Completed | 24 |
| Not completed | 0 |
| Milestone | Colchicine Alone / With Ritonavir (at Steady-state) |
|---|---|
| Started | 24 |
| Completed | 24 |
| Not completed | 0 |
| Milestone | Colchicine Alone / With Ritonavir (at Steady-state) |
|---|---|
| Started | 24 |
| Completed | 18 |
| Not completed | 6 |
| Withdrew: Liver panel out of range | 6 |
| Milestone | Colchicine Alone / With Ritonavir (at Steady-state) |
|---|---|
| Started | 18 |
| Completed | 17 |
| Not completed | 1 |
| Withdrew: Lost to follow-up | 1 |
The maximum or peak concentration that colchicine reaches in the plasma.
| pg/mL | Colchicine Alone | Colchicine With Ritonavir (at Steady-state) |
|---|---|---|
| Maximum Plasma Concentration (Cmax) | 1,869.50 ± 526.94 | 4,993.06 ± 1,257.07 |
The area under the 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.
| pg-hr/mL | Colchicine Alone | Colchicine With Ritonavir (at Steady-state) |
|---|---|---|
| Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] | 8,412.04 ± 3,992.34 | 29,048.45 ± 8,935.10 |
The area under the 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.
| pg-hr/mL | Colchicine Alone | Colchicine With Ritonavir (at Steady-state) |
|---|---|---|
| Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] | 10,410.73 ± 4,734.38 | 35,276.22 ± 10,508.55 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Colchicine Alone | — | 0/24 (0%) | — |
| Ritonavir Alone | — | 0/18 (0%) | — |
| Colchicine With Steady-state Ritonavir | — | 0/18 (0%) | — |
| Event | Colchicine Alone | Ritonavir Alone | Colchicine With Steady-state Ritonavir |
|---|---|---|---|
| sinus congestionRespiratory, thoracic and mediastinal disorders | 0/24 | 2/18 | 0/18 |
| rhinorrhoeaRespiratory, thoracic and mediastinal disorders | 2/24 | 0/18 | 0/18 |
| nauseaGastrointestinal disorders | 1/24 | 0/18 | 1/18 |
| dysgeusiaNervous system disorders | 1/24 | 0/18 | 1/18 |
| headacheNervous system disorders | 1/24 | 0/18 | 1/18 |
| dysmenorrhoeaReproductive system and breast disorders | 0/24 | 0/18 | 1/18 |
| coughRespiratory, thoracic and mediastinal disorders | 0/24 | 1/18 | 0/18 |
| pharyngolaryngeal painRespiratory, thoracic and mediastinal disorders | 0/24 | 1/18 | 0/18 |
| upper abdominal painGastrointestinal disorders | 1/24 | 0/18 | 0/18 |
| vomitingGastrointestinal disorders | 1/24 | 0/18 | 0/18 |
| Age, Categorical(Participants) | Colchicine Alone / With Ritonavir (at Steady-state) |
|---|---|
| <=18 years | 5 |
| Between 18 and 65 years | 19 |
| >=65 years | 0 |
| Age Continuous(years) | Colchicine Alone / With Ritonavir (at Steady-state) |
|---|---|
| Mean | 23.0 ± 4.7 |
| Sex: Female, Male(Participants) | Colchicine Alone / With Ritonavir (at Steady-state) |
|---|---|
| Female | 10 |
| Male | 14 |
| Race (NIH/OMB)(Participants) | Colchicine Alone / With Ritonavir (at Steady-state) |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 2 |
| White | 22 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Ethnicity (NIH/OMB)(Participants) | Colchicine Alone / With Ritonavir (at Steady-state) |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 24 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Colchicine Alone / With Ritonavir (at Steady-state) |
|---|---|
| United States | 24 |
This study is completed, as verified in Oct 2009. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Colchicine · Ritonavir
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