A Pharmacokinetic Study of Colchicine With an Oral Contraceptive
A Pharmacokinetic Study of Colchicine With an Oral Contraceptive
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.
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.
Inclusion Criteria:

 -  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

 Exclusion Criteria:

 -  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