Healthy
Conditions
Keywords
Healthy, bioavailability
Brief summary
The purpose of this study is to evaluate and compare the relative bioavailability of a single dose of Colcrys™ (colchicine) 0.6 mg when administered to a group of young , healthy subjects 18-30 years of age compared to a group of older, generally healthy subjects 60 years of age or older following an overnight fast.
Detailed description
The purpose of this study is to evaluate and compare the relative bioavailability of a single dose of Colcrys™ (colchicine) 0.6 mg when administered to a group of young, healthy subjects 18-30 years of age compared to a group of older, generally healthy subjects 60 years of age or older following an overnight fast. On study Day 1 following an overnight fast, twenty healthy, non-smoking, non-obese male and female subjects between the ages of 18 and 30 and twenty generally healthy, non-smoking, non-obese male and female subjects over 60 years of age will be administered one single dose of Colcrys™ (1 x 0.6 mg tablet). Fasting will continue for 4 hours after the dose. Blood samples will be drawn from all participants before dosing and for 24 hours post-dose on a confined basis at times sufficient to adequately define the pharmacokinetics of Colcrys. Blood sampling will continue on a non-confined basis at 36, 48, 60 and 72 hours post-dose. Subjects will be monitored throughout participation in the study for adverse reactions to the study drug and/or procedures. Vitals signs (temperature, respiratory rate, pulse rate and blood pressure) will be measured in the sitting position prior to dosing. Seated blood pressure and pulse will be measured at approximately 1, 3, 6 and 12 hours after dosing and prior to release from the facility. 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.
Interventions
DRUGColcrys™ (colchicine)
0.6 mg taken by mouth on day 1
Sponsors
Mutual Pharmaceutical Company, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy adults 18-30 years of age or generally healthy adults over 60 years of age (elderly subjects with minor renal impairment may be allowed to participate at the discretion of the investigator), non-smoking and non-pregnant (post-menopausal, surgically sterile or using effective contraceptive measures) with a body mass index (BMI) of 18-30 kg/m2.
Exclusion criteria
* Recent participation (within 30 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) * History of treatment for drug or alcohol addiction within the previous 12 months or excessive alcohol consumption during the past 12 months * Significant history of chronic infectious disease, system disorders, organ dysfunction, especially cardiovascular disorders (angina, heart failure, irregular heartbeats, heart attack, hypertension, hypotension) stroke, renal or hepatic disorder, diabetes or bleeding disorders, gastrointestinal disease or psychiatric disorders. * Presence of a medical condition requiring regular treatment with prescription drugs * Subjects who have used any drugs or substances known to inhibit or induce drug-metabolizing enzymes within 30 days prior to the first dose and throughout the study * Drug allergies or sensitivity to colchicine * Positive test results for drugs of abuse at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) | serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 16, 18, 24, 36, 48, 60 and 72 hours post-dose | The maximum or peak concentration that Colcrys™ (colchicine) reaches in the plasma. |
| Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] for Colcrys™ | serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 16, 18, 24, 36, 48, 60 and 72 hours post-dose | 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 plasma concentration to the elimination rate constant. |
| Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Colcrys™ | serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 16, 18, 24, 36, 48, 60 and 72 hours post-dose | The area under the plasma concentration versus time curve, from time 0 to the time of the last measurable concentration (t), as calculated by the linear trapezoidal rule. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Colcrys™ - Young Subjects and Colcrys™ - Elderly Subjects Colcrys™ (colchicine) - young subjects (18-30 years): All young subjects (18-30 years) received a single oral dose of Colcrys™ (1 x 0.6 mg) on Day 1 following an overnight fast of at least 10 hours.
Colcrys™ (colchicine) - Elderly subjects (≥60 years): All elderly subjects (≥ 60 years)received a single oral dose of Colcrys™ (1 x 0.6 mg) on Day 1 following an overnight fast of at least 10 hours. | 38 |
| Total | 38 |
Baseline characteristics
| Characteristic | Colcrys™ - Young Subjects and Colcrys™ - Elderly Subjects |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants |
| Age Continuous | 42.32 years STANDARD_DEVIATION 19.44 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment United States | 38 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 20 | 8 / 18 |
| serious Total, serious adverse events | 0 / 20 | 0 / 18 |
Outcome results
Primary
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] for Colcrys™
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 plasma concentration to the elimination rate constant.
Time frame: serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 16, 18, 24, 36, 48, 60 and 72 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Colcrys™ (Colchicine) - Young Subjects (18-30 Years Old) | Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] for Colcrys™ | 22.39 ng*hr/mL | Standard Deviation 6.95 |
| Colcrys™ (Colchicine) - Elderly Subjects ≥ 60 Years) | Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] for Colcrys™ | 25.01 ng*hr/mL | Standard Deviation 6.92 |
Primary
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Colcrys™
The area under the plasma concentration versus time curve, from time 0 to the time of the last measurable concentration (t), as calculated by the linear trapezoidal rule.
Time frame: serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 16, 18, 24, 36, 48, 60 and 72 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Colcrys™ (Colchicine) - Young Subjects (18-30 Years Old) | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Colcrys™ | 20.14 ng*hr/mL | Standard Deviation 5.85 |
| Colcrys™ (Colchicine) - Elderly Subjects ≥ 60 Years) | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Colcrys™ | 21.88 ng*hr/mL | Standard Deviation 6.22 |
Primary
Maximum Plasma Concentration (Cmax)
The maximum or peak concentration that Colcrys™ (colchicine) reaches in the plasma.
Time frame: serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 16, 18, 24, 36, 48, 60 and 72 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Colcrys™ (Colchicine) - Young Subjects (18-30 Years Old) | Maximum Plasma Concentration (Cmax) | 2.60 ng/mL | Standard Deviation 0.71 |
| Colcrys™ (Colchicine) - Elderly Subjects ≥ 60 Years) | Maximum Plasma Concentration (Cmax) | 2.56 ng/mL | Standard Deviation 0.97 |