A Pharmacokinetic Study to Evaluate the Effect of Colchicine on the Pharmacokinetic Profile of an Oral Contraceptive Containing Ethinyl Estradiol and Norethindrone in Healthy Women
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] Ethinyl Estradiol With Colchicine
研究概览
简要总结
This study will evaluate the effect, if any, of twice daily dosing of colchicine 0.6 mg at steady state on the steady state pharmacokinetic profile of ethinyl estradiol and norethindrone (Ortho-Novum 1/35). It will also evaluate the effects, if any, of steady state ethinyl estradiol and norethindrone on colchicine at steady state. Finally, this study will assess the safety and tolerability of concurrent use of colchicine and an estrogen/progesterone-containing oral contraceptive.
详细描述
This study will evaluate the effect, if any, of twice daily dosing of colchicine 0.6 mg at steady state on the steady state pharmacokinetic profile of ethinyl estradiol and norethindrone (Ortho-Novum 1/35). It will also evaluate the effects, if any, of steady state ethinyl estradiol and norethindrone on colchicine at steady state. Finally, this study will assess the safety and tolerability of concurrent use of colchicine and an estrogen/progesterone-containing oral contraceptive. Following an optional single cycle run-in period in which subjects taking other oral contraceptives are switched to Ortho-Novum 1/35, 30 healthy adult female volunteers of child bearing age (18-45 years old) will be randomized in a double blind crossover fashion to receive each of two ethinyl estradiol and norethindrone dosing regimens in sequence. During each of the two dosing periods, subjects will receive one ethinyl estradiol and norethindrone tablet on the mornings of Days 1-7 of their cycles. On days 8-21, subjects will receive twice daily doses of either colchicine (0.6 mg capsule twice daily with breakfast and dinner) or the placebo (one capsule twice daily with breakfast and dinner), according to their randomization schedule, along with one ethinyl estradiol and norethindrone tablet. Subjects will receive the alternate dosing regimen in Cycle 2. Blood samples will be drawn at times sufficient to determine the steady state pharmacokinetics of ethinyl estradiol and norethindrone with and without steady state colchicine. In addition, during the cycle in which active colchicine is given, the effect of steady state ethinyl estradiol and norethindrone on steady state colchicine will be evaluated. Subjects will be monitored for adverse effects throughout the study via query and spontaneous reporting. Additionally baseline 12 lead EKG and vital signs will be compared to those obtained at time points throughout the study period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Healthy, non-smoking female volunteers of childbearing potential aged 18 to 45 years weighing at least 55 kg and within 15% of ideal body weight who are taking oral contraceptives on the advice of their personal health care provider and willing to switch to Ortho-Novum 1/35
- •Subjects should be either sexually inactive or using a double barrier method of contraception for 14 days before the first dose of study drug and throughout the study
排除标准
- •Pregnant or lactating
- •Recent (2-year) history or evidence of alcoholism or drug abuse
- •Test positive at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C antibody (HCV)
- •History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease
- •Hemoglobin < 12 g/dL
- •Use of any drugs or substances known to inhibit or induce cytochrome (CYP) P450 enzymes and/or P-gp within 30 days prior to the first dose of Ortho-Novum® 1/35 or expected to require such use
研究组 & 干预措施
Oral Contraceptive with Colchicine then Placebo
干预措施: Norethindrone/Ethinyl Estradiol (Drug)
Oral Contraceptive with Colchicine then Placebo
干预措施: Colchicine (Drug)
Oral Contraceptive with Colchicine then Placebo
干预措施: Placebo (for Colchicine) (Drug)
Oral Contraceptive with Placebo then Colchicine
干预措施: Norethindrone/Ethinyl Estradiol (Drug)
Oral Contraceptive with Placebo then Colchicine
干预措施: Colchicine (Drug)
Oral Contraceptive with Placebo then Colchicine
干预措施: Placebo (for Colchicine) (Drug)
结局指标
主要结局
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] Ethinyl Estradiol With Colchicine
时间窗: serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 3.33, 3.67, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 14, 18, 24, 36, and 48 hours after drug administration.
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.
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Ethinyl Estradiol With Placebo
时间窗: Day 21 of each cycle - plasma concentrations were drawn prior to the morning dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 (prior to pm colchicine/placebo dose), and 24 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.
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Norethindrone With Placebo
时间窗: Day 21 of each cycle - plasma concentrations were drawn prior to the morning dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 (prior to pm colchicine/placebo dose), and 24 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.
Maximum Plasma Concentration of Ethinyl Estradiol With Placebo at Steady State (Cmax, ss)
时间窗: Day 21 of each cycle - plasma concentrations were drawn prior to the morning dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 (prior to pm colchicine/placebo dose), and 24 hours post-dose.
The maximum or peak concentration that Ethinyl Estradiol with Placebo reaches in the plasma at steady state. Steady state refers to the point that constant concentration of drug is achieved subsequent to administration of constant doses of that drug given at constant intervals.
Maximum Plasma Concentration of Norethindrone With Colchicine at Steady State (Cmax, ss)
时间窗: Day 21 of each cycle - plasma concentrations were drawn prior to the morning dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 (prior to pm colchicine/placebo dose), and 24 hours post-dose.
The maximum or peak concentration that Norethindrone with Colchicine reaches in the plasma at steady state. Steady state refers to the point that constant concentration of drug is achieved subsequent to administration of constant doses of that drug given at constant intervals.
Maximum Plasma Concentration of Ethinyl Estradiol With Colchicine at Steady State (Cmax, ss)
时间窗: Day 21 of each cycle - plasma concentrations were drawn prior to the morning dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 (prior to pm colchicine/placebo dose), and 24 hours post-dose.
The maximum or peak concentration that Ethinyl Estradiol with Colchicine reaches in the plasma at steady state. Steady state refers to the point that constant concentration of drug is achieved subsequent to administration of constant doses of that drug given at constant intervals.
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Norethindrone With Colchicine
时间窗: Day 21 of each cycle - plasma concentrations were drawn prior to the morning dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 (prior to pm colchicine/placebo dose), and 24 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.
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Colchicine With Norethindrone/Ethinyl Estradiol
时间窗: Day 21 of each cycle - plasma concentrations were drawn prior to the morning dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 (prior to pm colchicine/placebo dose), and 24 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.
Maximum Plasma Concentration of Norethindrone With Placebo at Steady State (Cmax, ss)
时间窗: Day 21 of each cycle - plasma concentrations were drawn prior to the morning dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 (prior to pm colchicine/placebo dose), and 24 hours post-dose.
The maximum or peak concentration that Norethindrone with Placebo reaches in the plasma at steady state. Steady state refers to the point that constant concentration of drug is achieved subsequent to administration of constant doses of that drug given at constant intervals.
Maximum Plasma Concentration of Colchicine With Norethindrone/Ethinyl Estradiol at Steady State (Cmax, ss)
时间窗: Day 21 of each cycle - plasma concentrations were drawn prior to the morning dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 (prior to pm colchicine/placebo dose), and 24 hours post-dose
The maximum or peak concentration that Colchicine with Norethindrone/Ethinyl Estradiol reaches in the plasma at steady state. Steady state refers to the point that constant concentration of drug is achieved subsequent to administration of constant doses of that drug given at constant intervals
次要结局
未报告次要终点