Official Title: “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”

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.

Study Type: Interventional

Study Design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Study Primary Completion Date: January 2008

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.

Intervention(s) in this Clinical Trial

• Drug: Norethindrone/Ethinyl Estradiol
  • one tablet daily - 1 mg norethindrone/0.035 mg ethinyl estradiol on Days 1 to 21; inert ingredients on Days 22 to 28
• Drug: Colchicine
  • 0.6mg tablet every 12 hours on Days 8 to 21
• Drug: Placebo (for Colchicine)
  • placebo tablet every 12 hours on Days 8 to 21

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Oral Contraceptive with Colchicine then Placebo
• Placebo Comparator: Oral Contraceptive with Placebo then Colchicine

Primary Measures

• Maximum Plasma Concentration of Norethindrone With Colchicine at Steady State (Cmax, ss)
  • Time Frame: 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.
    Safety Issue?: No
• Maximum Plasma Concentration of Norethindrone With Placebo at Steady State (Cmax, ss)
  • Time Frame: 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.
    Safety Issue?: No
• Maximum Plasma Concentration of Ethinyl Estradiol With Colchicine at Steady State (Cmax, ss)
  • Time Frame: 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.
    Safety Issue?: No
• Maximum Plasma Concentration of Ethinyl Estradiol With Placebo at Steady State (Cmax, ss)
  • Time Frame: 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.
    Safety Issue?: No
• Maximum Plasma Concentration of Colchicine With Norethindrone/Ethinyl Estradiol at Steady State (Cmax, ss)
  • Time Frame: 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
    Safety Issue?: No
• Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Norethindrone With Colchicine
  • Time Frame: 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.
    Safety Issue?: No
• Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Norethindrone With Placebo
  • Time Frame: 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.
    Safety Issue?: No
• Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] Ethinyl Estradiol With Colchicine
  • Time Frame: 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.
    Safety Issue?: No
• Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Ethinyl Estradiol With Placebo
  • Time Frame: 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.
    Safety Issue?: No
• Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Colchicine With Norethindrone/Ethinyl Estradiol
  • Time Frame: 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
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 45 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Mutual Pharmaceutical Company, Inc.

Information obtained from ClinicalTrials.gov on September 01, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01040845

Study ID Number: MPC-004-07-1005

ClinicalTrials.gov Identifier: NCT01040845

Health Authority: United States: Food and Drug Administration

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