Trial Outcomes & Findings for A Pharmacokinetic Study of Colchicine With an Oral Contraceptive (NCT NCT01040845)
NCT ID: NCT01040845
Last Updated: 2010-01-05
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
30 participants
Primary outcome timeframe
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.
Results posted on
2010-01-05
Participant Flow
Thirty (30) healthy, non-smoking, premenopausal adult female volunteers, consisting of university students and members of the community at large, were to be enrolled.
51 subjects screened, 21 were screen failures
Participant milestones
| Measure |
Oral Contraceptive With Placebo Then Colchicine
\[All subjects received each of the two study treatments in a randomly assigned sequence of two dosing cycles.\] 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.
|
Oral Contraceptive With Colchicine Then Placebo
\[All subjects received each of the two study treatments in a randomly assigned sequence of two dosing cycles.\] 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.
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
15
|
|
Overall Study
COMPLETED
|
13
|
14
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
Oral Contraceptive With Placebo Then Colchicine
\[All subjects received each of the two study treatments in a randomly assigned sequence of two dosing cycles.\] 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.
|
Oral Contraceptive With Colchicine Then Placebo
\[All subjects received each of the two study treatments in a randomly assigned sequence of two dosing cycles.\] 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.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
|
Overall Study
Physician Decision
|
1
|
0
|
Baseline Characteristics
A Pharmacokinetic Study of Colchicine With an Oral Contraceptive
Baseline characteristics by cohort
| Measure |
Oral Contraceptive With Placebo Then Colchicine
n=15 Participants
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).
|
Oral Contraceptive With Colchicine Then Placebo
n=15 Participants
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
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0.0 Participants
n=35 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
15 Participants
n=39 Participants
|
15 Participants
n=41 Participants
|
30.0 Participants
n=35 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0.0 Participants
n=35 Participants
|
|
Age Continuous
|
23.8 years
STANDARD_DEVIATION 7.9 • n=39 Participants
|
23.9 years
STANDARD_DEVIATION 4.2 • n=41 Participants
|
23.9 years
STANDARD_DEVIATION 6.3 • n=35 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=39 Participants
|
15 Participants
n=41 Participants
|
30.0 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0.0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0.0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0.0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0.0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0.0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=39 Participants
|
15 Participants
n=41 Participants
|
30.0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0.0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0.0 Participants
n=35 Participants
|
|
Region of Enrollment
United States
|
15 participants
n=39 Participants
|
15 participants
n=41 Participants
|
30.0 participants
n=35 Participants
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Norethindrone With Colchicine
n=27 Participants
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.
|
|---|---|
|
Maximum Plasma Concentration of Norethindrone With Colchicine at Steady State (Cmax, ss)
|
24.17 ng/mL
Standard Deviation 6.63
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Norethindrone With Colchicine
n=27 Participants
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.
|
|---|---|
|
Maximum Plasma Concentration of Norethindrone With Placebo at Steady State (Cmax, ss)
|
24.42 ng/mL
Standard Deviation 6.11
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Norethindrone With Colchicine
n=27 Participants
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.
|
|---|---|
|
Maximum Plasma Concentration of Ethinyl Estradiol With Colchicine at Steady State (Cmax, ss)
|
0.14 ng/mL
Standard Deviation 0.05
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Norethindrone With Colchicine
n=27 Participants
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.
|
|---|---|
|
Maximum Plasma Concentration of Ethinyl Estradiol With Placebo at Steady State (Cmax, ss)
|
0.15 ng/mL
Standard Deviation 0.05
|
PRIMARY outcome
Timeframe: 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-doseThe 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
Outcome measures
| Measure |
Norethindrone With Colchicine
n=27 Participants
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.
|
|---|---|
|
Maximum Plasma Concentration of Colchicine With Norethindrone/Ethinyl Estradiol at Steady State (Cmax, ss)
|
3.11 ng/mL
Standard Deviation 0.86
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Norethindrone With Colchicine
n=27 Participants
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.
|
|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Norethindrone With Colchicine
|
175.57 ng-hr/mL
Standard Deviation 60.74
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Norethindrone With Colchicine
n=27 Participants
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.
|
|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Norethindrone With Placebo
|
178.08 ng/mL
Standard Deviation 51.69
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Norethindrone With Colchicine
n=27 Participants
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.
|
|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] Ethinyl Estradiol With Colchicine
|
1.24 ng/mL
Standard Deviation 0.41
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Norethindrone With Colchicine
n=27 Participants
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.
|
|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Ethinyl Estradiol With Placebo
|
1.29 ng/mL
Standard Deviation 0.40
|
PRIMARY outcome
Timeframe: 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-doseThe 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.
Outcome measures
| Measure |
Norethindrone With Colchicine
n=27 Participants
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.
|
|---|---|
|
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Colchicine With Norethindrone/Ethinyl Estradiol
|
18.40 ng/mL
Standard Deviation 4.15
|
Adverse Events
Oral Contraceptive With Colchicine
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Oral Contraceptive With Colchicine
n=27 participants at risk
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.
|
|---|---|
|
Eye disorders
eye pain
|
3.7%
1/27 • Number of events 1
|
|
Eye disorders
eye discharge
|
3.7%
1/27 • Number of events 1
|
|
Eye disorders
ocular hyperaemia
|
3.7%
1/27 • Number of events 1
|
|
Gastrointestinal disorders
abdominal pain upper
|
11.1%
3/27 • Number of events 3
|
|
Gastrointestinal disorders
diarrhoea
|
18.5%
5/27 • Number of events 5
|
|
Gastrointestinal disorders
nausea
|
11.1%
3/27 • Number of events 3
|
|
Gastrointestinal disorders
stomach discomfort
|
3.7%
1/27 • Number of events 1
|
|
General disorders
fatigue
|
3.7%
1/27 • Number of events 1
|
|
General disorders
feeling hot
|
3.7%
1/27 • Number of events 1
|
|
Infections and infestations
paronychia
|
3.7%
1/27 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
back pain
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
dizziness
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
syncope
|
3.7%
1/27 • Number of events 1
|
|
Reproductive system and breast disorders
metrorrhagia
|
3.7%
1/27 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
nasal congestion
|
3.7%
1/27 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
pharyngolaryngeal pain
|
3.7%
1/27 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
cold sweat
|
7.4%
2/27 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
hyperhidrosis
|
3.7%
1/27 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
rash maculo-papular
|
3.7%
1/27 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60