Trial Outcomes & Findings for Co-Administration Of Methotrexate And CP-690,550 (NCT NCT01745055)
NCT ID: NCT01745055
Last Updated: 2013-02-04
Results Overview
AUC (0-12)= area under the plasma concentration time-curve from time zero (pre-dose) to 12 hours (0-12).
COMPLETED
PHASE1
12 participants
0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7
2013-02-04
Participant Flow
Participant milestones
| Measure |
Methotrexate + CP-690,550
Single oral dose of methotrexate (MTX) on Day 1 (15-25 milligram \[mg\], as per local prescribing practice); followed by CP-690,500 30 mg tablet orally every twelve hours from Day 3 to Day 6; followed by single oral dose of MTX (15-25 mg, as per local prescribing practice) and single oral dose of CP-690,500 30 mg tablet orally, on Day 7.
|
|---|---|
|
Overall Study
STARTED
|
12
|
|
Overall Study
COMPLETED
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Co-Administration Of Methotrexate And CP-690,550
Baseline characteristics by cohort
| Measure |
Methotrexate + CP-690,550
n=12 Participants
Single oral dose of methotrexate (MTX) on Day 1 (15-25 milligram \[mg\], as per local prescribing practice); followed by CP-690,500 30 mg tablet orally every twelve hours from Day 3 to Day 6; followed by single oral dose of MTX (15-25 mg, as per local prescribing practice) and single oral dose of CP-690,500 30 mg tablet orally, on Day 7.
|
|---|---|
|
Age Continuous
|
57.3 years
STANDARD_DEVIATION 10.2 • n=93 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7Population: The pharmacokinetic (PK) analysis population included all enrolled participants with PK parameters of interest for at least 1 period of fixed sequence.
AUC (0-12)= area under the plasma concentration time-curve from time zero (pre-dose) to 12 hours (0-12).
Outcome measures
| Measure |
CP-690,500
n=12 Participants
CP-690,500 30 mg tablet orally every twelve hours from Day 3 to Day 6.
|
Methotrexate + CP-690,500
n=12 Participants
Single oral dose of MTX (15-25 mg, as per local prescribing practice) and single oral dose of CP-690,500 30 mg tablet orally, on Day 7.
|
|---|---|---|
|
Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] for CP-690,550
|
1370 nanogram*hour/milliliter (ng*hr/mL)
Standard Deviation 423
|
1410 nanogram*hour/milliliter (ng*hr/mL)
Standard Deviation 425
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7Population: The PK analysis population included all enrolled participants with PK parameters of interest for at least 1 period of fixed sequence.
Outcome measures
| Measure |
CP-690,500
n=12 Participants
CP-690,500 30 mg tablet orally every twelve hours from Day 3 to Day 6.
|
Methotrexate + CP-690,500
n=12 Participants
Single oral dose of MTX (15-25 mg, as per local prescribing practice) and single oral dose of CP-690,500 30 mg tablet orally, on Day 7.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) for CP-690,550
|
375 ng/mL
Standard Deviation 91.6
|
384 ng/mL
Standard Deviation 84.8
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours post-dose on Day 1 and Day 7Population: PK analysis population included all enrolled participants with PK parameters of interest for at least 1 period of fixed sequence.
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Outcome measures
| Measure |
CP-690,500
n=12 Participants
CP-690,500 30 mg tablet orally every twelve hours from Day 3 to Day 6.
|
Methotrexate + CP-690,500
n=12 Participants
Single oral dose of MTX (15-25 mg, as per local prescribing practice) and single oral dose of CP-690,500 30 mg tablet orally, on Day 7.
|
|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Methotrexate (MTX)
|
1850 ng*hr/mL
Standard Deviation 685
|
1720 ng*hr/mL
Standard Deviation 753
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 24 and 48 hours post-dose on Day 1 and Day 7Population: PK analysis population included all enrolled participants with PK parameters of interest for at least 1 period of fixed sequence.
Outcome measures
| Measure |
CP-690,500
n=12 Participants
CP-690,500 30 mg tablet orally every twelve hours from Day 3 to Day 6.
|
Methotrexate + CP-690,500
n=12 Participants
Single oral dose of MTX (15-25 mg, as per local prescribing practice) and single oral dose of CP-690,500 30 mg tablet orally, on Day 7.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) for Methotrexate (MTX)
|
478 ng/mL
Standard Deviation 106
|
433 ng/mL
Standard Deviation 175
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7Population: PK analysis population included all enrolled participants with PK parameters of interest for at least 1 period of fixed sequence.
Outcome measures
| Measure |
CP-690,500
n=12 Participants
CP-690,500 30 mg tablet orally every twelve hours from Day 3 to Day 6.
|
Methotrexate + CP-690,500
n=12 Participants
Single oral dose of MTX (15-25 mg, as per local prescribing practice) and single oral dose of CP-690,500 30 mg tablet orally, on Day 7.
|
|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) for CP-690,550
|
1.00 hour
Interval 0.5 to 1.0
|
1.00 hour
Interval 0.5 to 1.0
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7Population: PK analysis population included all enrolled participants with PK parameters of interest for at least 1 period of fixed sequence.
Plasma decay half-life is the time measured for the plasma concentration of CP-690,550 to decrease by one half.
Outcome measures
| Measure |
CP-690,500
n=12 Participants
CP-690,500 30 mg tablet orally every twelve hours from Day 3 to Day 6.
|
Methotrexate + CP-690,500
n=12 Participants
Single oral dose of MTX (15-25 mg, as per local prescribing practice) and single oral dose of CP-690,500 30 mg tablet orally, on Day 7.
|
|---|---|---|
|
Plasma Decay Half-Life (t1/2) for CP-690,550
|
2.64 hour
Standard Deviation 0.356
|
3.12 hour
Standard Deviation 0.74
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7Population: PK analysis population included all enrolled participants with PK parameters of interest for at least 1 period of fixed sequence.
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Outcome measures
| Measure |
CP-690,500
n=12 Participants
CP-690,500 30 mg tablet orally every twelve hours from Day 3 to Day 6.
|
Methotrexate + CP-690,500
n=12 Participants
Single oral dose of MTX (15-25 mg, as per local prescribing practice) and single oral dose of CP-690,500 30 mg tablet orally, on Day 7.
|
|---|---|---|
|
Apparent Oral Clearance (CL/F) for CP-690,550
|
23200 mL/hr
Standard Deviation 8380
|
23511 mL/hr
Standard Deviation 8784
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 ,12, 24 and 48 hours post-dose on Day 1 and Day 7Population: PK analysis population included all enrolled participants with PK parameters of interest for at least 1 period of fixed sequence.
Outcome measures
| Measure |
CP-690,500
n=12 Participants
CP-690,500 30 mg tablet orally every twelve hours from Day 3 to Day 6.
|
Methotrexate + CP-690,500
n=12 Participants
Single oral dose of MTX (15-25 mg, as per local prescribing practice) and single oral dose of CP-690,500 30 mg tablet orally, on Day 7.
|
|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Methotrexate (MTX)
|
1.00 hour
Interval 0.5 to 1.5
|
1.25 hour
Interval 0.5 to 2.0
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 , 12, 24 and 48 hours post-dose on Day 1 and Day 7Population: PK analysis population included all enrolled participants with PK parameters of interest for at least 1 period of fixed sequence.
Plasma decay half-life is the time measured for the plasma concentration of MTX to decrease by one half.
Outcome measures
| Measure |
CP-690,500
n=12 Participants
CP-690,500 30 mg tablet orally every twelve hours from Day 3 to Day 6.
|
Methotrexate + CP-690,500
n=12 Participants
Single oral dose of MTX (15-25 mg, as per local prescribing practice) and single oral dose of CP-690,500 30 mg tablet orally, on Day 7.
|
|---|---|---|
|
Plasma Decay Half-Life (t1/2) for Methotrexate (MTX)
|
2.87 hour
Standard Deviation 0.962
|
3.36 hour
Standard Deviation 1.13
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 , 12, 24 and 48 hours post-dose on Day 1 and Day 7Population: PK analysis population included all enrolled participants with PK parameters of interest for at least 1 period of fixed sequence.
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Outcome measures
| Measure |
CP-690,500
n=12 Participants
CP-690,500 30 mg tablet orally every twelve hours from Day 3 to Day 6.
|
Methotrexate + CP-690,500
n=12 Participants
Single oral dose of MTX (15-25 mg, as per local prescribing practice) and single oral dose of CP-690,500 30 mg tablet orally, on Day 7.
|
|---|---|---|
|
Apparent Oral Clearance (CL/F) for Methotrexate (MTX)
|
9890 mL/hr
Standard Deviation 3370
|
11500 mL/hr
Standard Deviation 5430
|
SECONDARY outcome
Timeframe: 0 (pre-dose) through 12 hours post-dose on Day 6 and Day 7Population: PK analysis population included all enrolled participants with PK parameters of interest for at least 1 period of fixed sequence.
Outcome measures
| Measure |
CP-690,500
n=12 Participants
CP-690,500 30 mg tablet orally every twelve hours from Day 3 to Day 6.
|
Methotrexate + CP-690,500
n=12 Participants
Single oral dose of MTX (15-25 mg, as per local prescribing practice) and single oral dose of CP-690,500 30 mg tablet orally, on Day 7.
|
|---|---|---|
|
Total Amount of Unchanged Drug Excreted in the Urine From Time Zero to 12 Hours (Ae[0-12]) for CP-690,550
|
6.65 milligram
Standard Deviation 2.26
|
6.58 milligram
Standard Deviation 2.34
|
SECONDARY outcome
Timeframe: 0 (pre-dose) through 24 hours post-dose on Day 6 and Day 7Population: PK analysis population included all enrolled participants with PK parameters of interest for at least 1 period of fixed sequence.
Outcome measures
| Measure |
CP-690,500
n=12 Participants
CP-690,500 30 mg tablet orally every twelve hours from Day 3 to Day 6.
|
Methotrexate + CP-690,500
n=12 Participants
Single oral dose of MTX (15-25 mg, as per local prescribing practice) and single oral dose of CP-690,500 30 mg tablet orally, on Day 7.
|
|---|---|---|
|
Renal Clearance (CL R) for CP-690,550
|
5490 litre/hour (L/hr)
Standard Deviation 2890
|
5240 litre/hour (L/hr)
Standard Deviation 2630
|
SECONDARY outcome
Timeframe: 0 (pre-dose) through 24 hours post-dose on Day 1 and Day 7Population: PK analysis population included all enrolled participants with PK parameters of interest for at least 1 period of fixed sequence.
Outcome measures
| Measure |
CP-690,500
n=12 Participants
CP-690,500 30 mg tablet orally every twelve hours from Day 3 to Day 6.
|
Methotrexate + CP-690,500
n=12 Participants
Single oral dose of MTX (15-25 mg, as per local prescribing practice) and single oral dose of CP-690,500 30 mg tablet orally, on Day 7.
|
|---|---|---|
|
Total Amount of Unchanged Drug Excreted in the Urine From Time Zero to 24 Hours (Ae[0-24]) for Methotrexate (MTX)
|
18.1 milligram
Standard Deviation 9.31
|
13.2 milligram
Standard Deviation 4.38
|
SECONDARY outcome
Timeframe: 0 (pre-dose) through 24 hours post-dose on Day 1 and Day 7Population: PK analysis population included all enrolled participants with PK parameters of interest for at least 1 period of fixed sequence.
Outcome measures
| Measure |
CP-690,500
n=12 Participants
CP-690,500 30 mg tablet orally every twelve hours from Day 3 to Day 6.
|
Methotrexate + CP-690,500
n=12 Participants
Single oral dose of MTX (15-25 mg, as per local prescribing practice) and single oral dose of CP-690,500 30 mg tablet orally, on Day 7.
|
|---|---|---|
|
Renal Clearance (CL R) for Methotrexate (MTX)
|
10.2 L/hr
Standard Deviation 4.56
|
8.95 L/hr
Standard Deviation 4.64
|
Adverse Events
Methotrexate
CP-690,500
Methotrexate + CP-690,500
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Methotrexate
n=12 participants at risk
Single oral dose of MTX on Day 1 (15-25 mg), as per local prescribing practice.
|
CP-690,500
n=12 participants at risk
CP-690,500 30 mg tablet orally every twelve hours from Day 3 to Day 6.
|
Methotrexate + CP-690,500
n=12 participants at risk
Single oral dose of MTX (15-25 mg, as per local prescribing practice) and single oral dose of CP-690,500 30 mg tablet orally, on Day 7.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/12
|
0.00%
0/12
|
16.7%
2/12
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/12
|
16.7%
2/12
|
8.3%
1/12
|
|
Infections and infestations
Sinusitis
|
8.3%
1/12
|
8.3%
1/12
|
8.3%
1/12
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.3%
1/12
|
8.3%
1/12
|
8.3%
1/12
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.3%
1/12
|
8.3%
1/12
|
8.3%
1/12
|
|
Musculoskeletal and connective tissue disorders
Muscle fatigue
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
8.3%
1/12
|
8.3%
1/12
|
8.3%
1/12
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/12
|
8.3%
1/12
|
8.3%
1/12
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
0.00%
0/12
|
8.3%
1/12
|
8.3%
1/12
|
|
Nervous system disorders
Dizziness
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
|
Nervous system disorders
Headache
|
16.7%
2/12
|
8.3%
1/12
|
0.00%
0/12
|
|
Nervous system disorders
Migrane
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
|
Nervous system disorders
Syncope vasovagal
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
|
Nervous system disorders
Tension headache
|
0.00%
0/12
|
8.3%
1/12
|
8.3%
1/12
|
|
Psychiatric disorders
Disorientation
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
|
Vascular disorders
Hot flush
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER