A Pharmacokinetic Study of Colchicine With an Oral Contraceptive

This study has been completed.
Sponsor:
Information provided by:
Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier:
NCT01040845
First received: August 13, 2009
Last updated: December 30, 2009
Last verified: December 2009
  Purpose

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.


Condition Intervention Phase
Pharmacokinetics
Drug: Norethindrone/Ethinyl Estradiol
Drug: Colchicine
Drug: Placebo (for Colchicine)
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Mutual Pharmaceutical Company, Inc.:

Primary Outcome 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. ] [ Designated as 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. ] [ Designated as 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. ] [ Designated as 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. ] [ Designated as 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 ] [ Designated as 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. ] [ Designated as 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. ] [ Designated as 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. ] [ Designated as 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. ] [ Designated as 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 ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: August 2007
Study Completion Date: February 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral Contraceptive with Colchicine then Placebo 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
Other Name: COLCRYS TM
Drug: Placebo (for Colchicine)
placebo tablet every 12 hours on Days 8 to 21
Placebo Comparator: Oral Contraceptive with Placebo then Colchicine 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
Other Name: COLCRYS TM
Drug: Placebo (for Colchicine)
placebo tablet every 12 hours on Days 8 to 21

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01040845

Locations
United States, North Dakota
PRACS Institute, Ltd. - Cetero Research
Fargo, North Dakota, United States, 58104
Sponsors and Collaborators
Mutual Pharmaceutical Company, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Vice President Branded Products and Medical Affairs, Mutual Pharmaceutical Company, Inc.
ClinicalTrials.gov Identifier: NCT01040845     History of Changes
Other Study ID Numbers: MPC-004-07-1005
Study First Received: August 13, 2009
Results First Received: August 13, 2009
Last Updated: December 30, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Mutual Pharmaceutical Company, Inc.:
healthy
pharmacokinetics
drug-interaction

Additional relevant MeSH terms:
Colchicine
Contraceptive Agents
Estradiol valerate
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Norethindrone
Norethindrone acetate
Norinyl
Ethynylestradiol mixture with norethindrone
Contraceptives, Oral
Estradiol
Polyestradiol phosphate
Ethinyl Estradiol
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptive Agents, Female
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Contraceptives, Oral, Synthetic
Contraceptives, Oral, Combined

ClinicalTrials.gov processed this record on August 28, 2014