A Pharmacokinetic Study of Colchicine With an Oral Contraceptive
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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 Names:
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 Names:
Drug: Placebo (for Colchicine)
placebo tablet every 12 hours on Days 8 to 21
|
Outcome Measures
Primary Outcome Measures
- Maximum Plasma Concentration of Norethindrone With Colchicine at Steady State (Cmax, ss) [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 Norethindrone With Placebo at Steady State (Cmax, ss) [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 Ethinyl Estradiol With Colchicine at Steady State (Cmax, ss) [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.
- Maximum Plasma Concentration of Ethinyl Estradiol With Placebo at Steady State (Cmax, ss) [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 Colchicine With Norethindrone/Ethinyl Estradiol at Steady State (Cmax, ss) [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
- Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Norethindrone With Colchicine [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 [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)] Ethinyl Estradiol With Colchicine [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 [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 [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.
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | PRACS Institute, Ltd. - Cetero Research | Fargo | North Dakota | United States | 58104 |
Sponsors and Collaborators
- Mutual Pharmaceutical Company, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- MPC-004-07-1005
Study Results
Participant Flow
| Recruitment Details | Thirty (30) healthy, non-smoking, premenopausal adult female volunteers, consisting of university students and members of the community at large, were to be enrolled. |
|---|---|
| Pre-assignment Detail | 51 subjects screened, 21 were screen failures |
| Arm/Group Title | Oral Contraceptive With Placebo Then Colchicine | Oral Contraceptive With Colchicine Then Placebo |
|---|---|---|
| Arm/Group Description | [All subjects received each of the two study treatments in a randomly assigned sequence of two dosing cycles.] On the mornings of Days 1 to 20 of each cycle, each subject took one active tablet of Ortho-Novum 1/35. On Days 8 to 20, subjects additionally took one capsule of study drug (matching placebo capsule during the first cycle or over-encapsulated colchicine tablets 0.6 mg during the second cycle) twice daily. On Day 21 of each cycle, subjects received a single dose of study drug and a single active tablet of Ortho-Novum 1/35; then, 12 hours later, they received a second dose of study drug with a light snack. Inert Ortho-Novum 1/35 tablets were taken on Day 22 (after breakfast and the last blood sample), and then daily on Days 23 to 28. | [All subjects received each of the two study treatments in a randomly assigned sequence of two dosing cycles.] On the mornings of Days 1 to 20 of each cycle, each subject took one active tablet of Ortho-Novum 1/35. On Days 8 to 20, subjects additionally took one capsule of study drug (over-encapsulated colchicine tablets 0.6 mg during or matching placebo capsule during the second cycle) twice daily. On Day 21 of each cycle, subjects received a single dose of study drug and a single active tablet of Ortho-Novum 1/35; then, 12 hours later, they received a second dose of study drug with a light snack. Inert Ortho-Novum 1/35 tablets were taken on Day 22 (after breakfast and the last blood sample), and then daily on Days 23 to 28. |
| Period Title: Overall Study | ||
| STARTED | 15 | 15 |
| COMPLETED | 13 | 14 |
| NOT COMPLETED | 2 | 1 |
Baseline Characteristics
| Arm/Group Title | Oral Contraceptive With Placebo Then Colchicine | Oral Contraceptive With Colchicine Then Placebo | Total |
|---|---|---|---|
| Arm/Group Description | All subjects received each of the two study treatments in a randomly assigned sequence of two dosing cycles. On the mornings of Days 1 to 20 of each cycle, each subject took one active tablet of Ortho-Novum 1/35. On Days 8 to 20 of each cycle, subjects additionally took one capsule of study drug (either over-encapsulated colchicine tablets 0.6 mg or a matching placebo capsule) twice daily in the morning and with dinner. On Day 21 of each cycle, subjects received a single dose of study drug and a single active tablet of Ortho-Novum 1/35; then, 12 hours later, they received a second dose of study drug with a light snack. Inert Ortho-Novum 1/35 tablets were taken on Day 22 (after breakfast and the last blood sample). | All subjects received each of the two study treatments in a randomly assigned sequence of two dosing cycles. On the mornings of Days 1 to 20 of each cycle, each subject took one active tablet of Ortho-Novum 1/35. On Days 8 to 20 of each cycle, subjects additionally took one capsule of study drug (either over-encapsulated colchicine tablets 0.6 mg or a matching placebo capsule) twice daily in the morning and with dinner. On Day 21 of each cycle, subjects received a single dose of study drug and a single active tablet of Ortho-Novum 1/35; then, 12 hours later, they received a second dose of study drug with a light snack. Inert Ortho-Novum 1/35 tablets were taken on Day 22 (after breakfast and the last blood sample). | Total of all reporting groups |
| Overall Participants | 15 | 15 | 30 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0.0
0%
|
| Between 18 and 65 years |
15
100%
|
15
100%
|
30.0
100%
|
| >=65 years |
0
0%
|
0
0%
|
0.0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
23.8
(7.9)
|
23.9
(4.2)
|
23.9
(6.3)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
15
100%
|
15
100%
|
30.0
100%
|
| Male |
0
0%
|
0
0%
|
0.0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0.0
0%
|
| Asian |
0
0%
|
0
0%
|
0.0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0.0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0.0
0%
|
| White |
15
100%
|
15
100%
|
30.0
100%
|
| More than one race |
0
0%
|
0
0%
|
0.0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0.0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
15
100%
|
15
100%
|
30.0
100%
|
Outcome Measures
| Title | Maximum Plasma Concentration of Norethindrone With Colchicine at Steady State (Cmax, ss) |
|---|---|
| Description | 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. |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Norethindrone With Colchicine |
|---|---|
| Arm/Group Description | On the mornings of Days 1 to 20, each subject took one active tablet of Ortho-Novum 1/35. On Days 8 to 20, subjects additionally took one colchicine tablet 0.6 mg (over-encapsulated to match placebo) twice daily, in the morning and with dinner. On Day 21, subjects received a single dose of colchicine 0.6 mg and a single active tablet of Ortho-Novum 1/35; then, 12 hours later, they received a second dose of colchicine 0.6 mg with a light snack. Inert Ortho-Novum 1/35 tablets were taken on Day 22 (after breakfast and the last blood sample), and then daily on Days 23 through 28. |
| Measure Participants | 27 |
| Mean (Standard Deviation) [ng/mL] |
24.17
(6.63)
|
| Title | Maximum Plasma Concentration of Norethindrone With Placebo at Steady State (Cmax, ss) |
|---|---|
| Description | 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. |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Norethindrone With Placebo |
|---|---|
| Arm/Group Description | On the mornings of Days 1 to 20, each subject took one active tablet of Ortho-Novum 1/35. On Days 8 to 20, subjects additionally took one placebo capsule twice daily in the morning and with dinner. On Day 21, subjects received a single dose of placebo and a single active tablet of Ortho-Novum 1/35; then, 12 hours later, they received a second dose of placebo with a light snack. Inert Ortho-Novum 1/35 tablets were taken on Day 22 (after breakfast and the last blood sample), and then daily on Days 23 through 28. |
| Measure Participants | 27 |
| Mean (Standard Deviation) [ng/mL] |
24.42
(6.11)
|
| Title | Maximum Plasma Concentration of Ethinyl Estradiol With Colchicine at Steady State (Cmax, ss) |
|---|---|
| Description | 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. |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Ethinyl Estradiol With Colchicine |
|---|---|
| Arm/Group Description | On the mornings of Days 1 to 20, each subject took one active tablet of Ortho-Novum 1/35. On Days 8 to 20, subjects additionally took one colchicine tablet 0.6 mg (over-encapsulated to match placebo) twice daily, in the morning and with dinner. On Day 21, subjects received a single dose of colchicine 0.6 mg and a single active tablet of Ortho-Novum 1/35; then, 12 hours later, they received a second dose of colchicine 0.6 mg with a light snack. Inert Ortho-Novum 1/35 tablets were taken on Day 22 (after breakfast and the last blood sample), and then daily on Days 23 through 28. |
| Measure Participants | 27 |
| Mean (Standard Deviation) [ng/mL] |
0.14
(0.05)
|
| Title | Maximum Plasma Concentration of Ethinyl Estradiol With Placebo at Steady State (Cmax, ss) |
|---|---|
| Description | 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. |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Ethinyl Estradiol With Placebo |
|---|---|
| Arm/Group Description | On the mornings of Days 1 to 20, each subject took one active tablet of Ortho-Novum 1/35. On Days 8 to 20, subjects additionally took one placebo capsule twice daily in the morning and with dinner. On Day 21, subjects received a single dose of placebo and a single active tablet of Ortho-Novum 1/35; then, 12 hours later, they received a second dose of placebo with a light snack. Inert Ortho-Novum 1/35 tablets were taken on Day 22 (after breakfast and the last blood sample), and then daily on Days 23 through 28. |
| Measure Participants | 27 |
| Mean (Standard Deviation) [ng/mL] |
0.15
(0.05)
|
| Title | Maximum Plasma Concentration of Colchicine With Norethindrone/Ethinyl Estradiol at Steady State (Cmax, ss) |
|---|---|
| Description | 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 |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Colchicine With Norethindrone/Ethinyl Estradiol |
|---|---|
| Arm/Group Description | On the mornings of Days 1 to 20, each subject took one active tablet of Ortho-Novum 1/35. On Days 8 to 20, subjects additionally took one colchicine tablet 0.6 mg (over-encapsulated to match placebo) twice daily, in the morning and with dinner. On Day 21, subjects received a single dose of colchicine 0.6 mg and a single active tablet of Ortho-Novum 1/35; then, 12 hours later, they received a second dose of colchicine 0.6 mg with a light snack. Inert Ortho-Novum 1/35 tablets were taken on Day 22 (after breakfast and the last blood sample), and then daily on Days 23 through 28. |
| Measure Participants | 27 |
| Mean (Standard Deviation) [ng/mL] |
3.11
(0.86)
|
| Title | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Norethindrone With Colchicine |
|---|---|
| Description | 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 | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Norethindrone With Colchicine |
|---|---|
| Arm/Group Description | On the mornings of Days 1 to 20, each subject took one active tablet of Ortho-Novum 1/35. On Days 8 to 20, subjects additionally took one colchicine tablet 0.6 mg (over-encapsulated to match placebo) twice daily, in the morning and with dinner. On Day 21, subjects received a single dose of colchicine 0.6 mg and a single active tablet of Ortho-Novum 1/35; then, 12 hours later, they received a second dose of colchicine 0.6 mg with a light snack. Inert Ortho-Novum 1/35 tablets were taken on Day 22 (after breakfast and the last blood sample), and then daily on Days 23 through 28. |
| Measure Participants | 27 |
| Mean (Standard Deviation) [ng-hr/mL] |
175.57
(60.74)
|
| Title | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Norethindrone With Placebo |
|---|---|
| Description | 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 | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Norethindrone With Placebo |
|---|---|
| Arm/Group Description | On the mornings of Days 1 to 20, each subject took one active tablet of Ortho-Novum 1/35. On Days 8 to 20, subjects additionally took one placebo capsule twice daily in the morning and with dinner. On Day 21, subjects received a single dose of placebo and a single active tablet of Ortho-Novum 1/35; then, 12 hours later, they received a second dose of placebo with a light snack. Inert Ortho-Novum 1/35 tablets were taken on Day 22 (after breakfast and the last blood sample), and then daily on Days 23 through 28. |
| Measure Participants | 27 |
| Mean (Standard Deviation) [ng/mL] |
178.08
(51.69)
|
| Title | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] Ethinyl Estradiol With Colchicine |
|---|---|
| Description | 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 0.33, 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Ethinyl Estradiol With Colchicine |
|---|---|
| Arm/Group Description | On the mornings of Days 1 to 20, each subject took one active tablet of Ortho-Novum 1/35. On Days 8 to 20, subjects additionally took one colchicine tablet 0.6 mg (over-encapsulated to match placebo) twice daily, in the morning and with dinner. On Day 21, subjects received a single dose of colchicine 0.6 mg and a single active tablet of Ortho-Novum 1/35; then, 12 hours later, they received a second dose of colchicine 0.6 mg with a light snack. Inert Ortho-Novum 1/35 tablets were taken on Day 22 (after breakfast and the last blood sample), and then daily on Days 23 through 28. |
| Measure Participants | 27 |
| Mean (Standard Deviation) [ng/mL] |
1.24
(0.41)
|
| Title | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Ethinyl Estradiol With Placebo |
|---|---|
| Description | 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 | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Ethinyl Estradiol With Placebo |
|---|---|
| Arm/Group Description | On the mornings of Days 1 to 20, each subject took one active tablet of Ortho-Novum 1/35. On Days 8 to 20, subjects additionally took one placebo capsule twice daily in the morning and with dinner. On Day 21, subjects received a single dose of placebo and a single active tablet of Ortho-Novum 1/35; then, 12 hours later, they received a second dose of placebo with a light snack. Inert Ortho-Novum 1/35 tablets were taken on Day 22 (after breakfast and the last blood sample), and then daily on Days 23 through 28. |
| Measure Participants | 27 |
| Mean (Standard Deviation) [ng/mL] |
1.29
(0.40)
|
| Title | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Colchicine With Norethindrone/Ethinyl Estradiol |
|---|---|
| Description | 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 | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Colchicine With Norethindrone/Ethinyl Estradiol |
|---|---|
| Arm/Group Description | On the mornings of Days 1 to 20, each subject took one active tablet of Ortho-Novum 1/35. On Days 8 to 20, subjects additionally took one colchicine tablet 0.6 mg (over-encapsulated to match placebo) twice daily, in the morning and with dinner. On Day 21, subjects received a single dose of colchicine 0.6 mg and a single active tablet of Ortho-Novum 1/35; then, 12 hours later, they received a second dose of colchicine 0.6 mg with a light snack. Inert Ortho-Novum 1/35 tablets were taken on Day 22 (after breakfast and the last blood sample), and then daily on Days 23 through 28. |
| Measure Participants | 27 |
| Mean (Standard Deviation) [ng/mL] |
18.40
(4.15)
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Oral Contraceptive With Colchicine | |
| Arm/Group Description | On the mornings of Days 1 to 20, each subject took one active tablet of Ortho-Novum 1/35. On Days 8 to 20 of each cycle, subjects additionally took one colchicine tablet 0.6 mg (over-encapsulated to match placebo) twice daily, in the morning and with dinner. On Day 21 of each cycle, subjects received a single dose of colchicine 0.6 mg and a single active tablet of Ortho-Novum 1/35; then, 12 hours later, they received a second dose of colchicine 0.6 mg with a light snack. Inert Ortho-Novum 1/35 tablets were taken on Day 22 (after breakfast and the last blood sample), and then daily on Days 23 through 28. | |
All Cause Mortality |
||
| Oral Contraceptive With Colchicine | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Oral Contraceptive With Colchicine | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/27 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Oral Contraceptive With Colchicine | ||
| Affected / at Risk (%) | # Events | |
| Total | 10/ (NaN) | |
| Eye disorders | ||
| eye pain | 1/27 (3.7%) | 1 |
| eye discharge | 1/27 (3.7%) | 1 |
| ocular hyperaemia | 1/27 (3.7%) | 1 |
| Gastrointestinal disorders | ||
| abdominal pain upper | 3/27 (11.1%) | 3 |
| diarrhoea | 5/27 (18.5%) | 5 |
| nausea | 3/27 (11.1%) | 3 |
| stomach discomfort | 1/27 (3.7%) | 1 |
| General disorders | ||
| fatigue | 1/27 (3.7%) | 1 |
| feeling hot | 1/27 (3.7%) | 1 |
| Infections and infestations | ||
| paronychia | 1/27 (3.7%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| back pain | 1/27 (3.7%) | 1 |
| Nervous system disorders | ||
| dizziness | 1/27 (3.7%) | 1 |
| syncope | 1/27 (3.7%) | 1 |
| Reproductive system and breast disorders | ||
| metrorrhagia | 1/27 (3.7%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| nasal congestion | 1/27 (3.7%) | 1 |
| pharyngolaryngeal pain | 1/27 (3.7%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| cold sweat | 2/27 (7.4%) | 2 |
| hyperhidrosis | 1/27 (3.7%) | 1 |
| rash maculo-papular | 1/27 (3.7%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Mutual Pharmaceutical Company, Inc. |
| Phone | 215-697-1743 |
| clinicaltrials@urlmutual.com |
- MPC-004-07-1005