Trial Outcomes & Findings for CP-690,550 Thorough QTc Study (NCT NCT01743677)
NCT ID: NCT01743677
Last Updated: 2020-09-16
Results Overview
Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to the beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as Least Squares (LS) mean difference (CP-690,550 minus Placebo, baseline-adjusted).
COMPLETED
PHASE1
60 participants
0.25 hour post-dose
2020-09-16
Participant Flow
Participant milestones
| Measure |
CP-690,550 100 mg Then Placebo Then Moxifloxacin 400 mg
Single oral dose of CP-690,550 100 milligram (mg) (5 x 20 mg tablets) in first intervention period; followed by single oral dose of placebo matched to CP-690,550 tablets in second intervention period; and single oral dose of moxifloxacin 400 mg tablet in third intervention period. A washout period of at least 7 days was maintained between each intervention period.
|
CP-690,550 100 mg Then Moxifloxacin 400 mg Then Placebo
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in first intervention period; followed by single oral dose of moxifloxacin 400 mg tablet in second intervention period; and single oral dose of placebo matched to CP-690,550 tablets in third intervention period. A washout period of at least 7 days was maintained between each intervention period.
|
Placebo Then CP-690,550 100 mg Then Moxifloxacin 400 mg
Single oral dose of placebo matched to CP-690,550 tablets in first intervention period; followed by single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in second intervention period; and single oral dose of moxifloxacin 400 mg tablet in third intervention period. A washout period of at least 7 days was maintained between each intervention period.
|
Placebo Then Moxifloxacin 400 mg Then CP-690,550 100 mg
Single oral dose of placebo matched to CP-690,550 tablets in first intervention period; followed by single oral dose of moxifloxacin 400 mg tablet in second intervention period; and single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in third intervention period. A washout period of at least 7 days was maintained between each intervention period.
|
Moxifloxacin 400 mg Then CP-690,550 100 mg Then Placebo
Single oral dose of moxifloxacin 400 mg tablet in first intervention period; followed by single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in second intervention period; and single oral dose of placebo matched to CP-690,550 tablets in third intervention period. A washout period of at least 7 days was maintained between each intervention period.
|
Moxifloxacin 400 mg Then Placebo Then CP-690,550 100 mg
Single oral dose of moxifloxacin 400 mg tablet in first intervention period; followed by single oral dose of placebo matched to CP-690,550 tablets in second intervention period; and single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in third intervention period. A washout period of at least 7 days was maintained between each intervention period.
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Third Intervention Period
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
CP-690,550 Thorough QTc Study
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=60 Participants
Includes participants randomized to receive any treatment (CP-690,550 100 mg first, moxifloxacin 400 mg first, or placebo first).
|
|---|---|
|
Age, Continuous
|
32.7 years
STANDARD_DEVIATION 9.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0.25 hour post-dosePopulation: ECG analysis set included all randomized and treated participants who had at least 1 post-dose ECG measurement in at least 1 period of the crossover.
Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to the beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as Least Squares (LS) mean difference (CP-690,550 minus Placebo, baseline-adjusted).
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
n=60 Participants
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 0.25 Hour Post-Dose
|
416.48 milliseconds (msec)
Standard Error 0.8823
|
417.77 milliseconds (msec)
Standard Error 0.8823
|
PRIMARY outcome
Timeframe: 0.5 hour post-dosePopulation: ECG analysis set included all randomized and treated participants who had at least 1 post-dose ECG measurement in at least 1 period of the crossover.
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The QT interval was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as LS mean difference (CP-690,550 minus Placebo, baseline-adjusted).
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
n=60 Participants
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 0.5 Hour Post-Dose
|
414.70 msec
Standard Error 0.8823
|
416.12 msec
Standard Error 0.8823
|
PRIMARY outcome
Timeframe: 1 hour post-dosePopulation: ECG analysis set included all randomized and treated participants who had at least 1 post-dose ECG measurement in at least 1 period of the crossover.
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The QT interval was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as LS mean difference (CP-690,550 minus Placebo, baseline-adjusted).
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
n=60 Participants
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 1 Hour Post-Dose
|
414.69 msec
Standard Error 0.8823
|
416.98 msec
Standard Error 0.8823
|
PRIMARY outcome
Timeframe: 2 hours post-dosePopulation: ECG analysis set included all randomized and treated participants who had at least 1 post-dose ECG measurement in at least 1 period of the crossover.
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The QT interval was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as LS mean difference (CP-690,550 minus Placebo, baseline-adjusted).
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
n=60 Participants
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 2 Hours Post-Dose
|
413.70 msec
Standard Error 0.8823
|
415.05 msec
Standard Error 0.8823
|
PRIMARY outcome
Timeframe: 4 hours post-dosePopulation: ECG analysis set included all randomized and treated participants who had at least 1 post-dose ECG measurement in at least 1 period of the crossover.
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The QT interval was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as LS mean difference (CP-690,550 minus Placebo, baseline-adjusted).
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
n=60 Participants
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 4 Hours Post-Dose
|
416.83 msec
Standard Error 0.8823
|
415.76 msec
Standard Error 0.8823
|
PRIMARY outcome
Timeframe: 8 hours post-dosePopulation: ECG analysis set included all randomized and treated participants who had at least 1 post-dose ECG measurement in at least 1 period of the crossover.
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The QT interval was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as LS mean difference (CP-690,550 minus Placebo, baseline-adjusted).
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
n=60 Participants
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 8 Hours Post-Dose
|
409.25 msec
Standard Error 0.8823
|
408.39 msec
Standard Error 0.8823
|
PRIMARY outcome
Timeframe: 12 hours post-dosePopulation: ECG analysis set included all randomized and treated participants who had at least 1 post-dose ECG measurement in at least 1 period of the crossover.
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The QT interval was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as LS mean difference (CP-690,550 minus Placebo, baseline-adjusted).
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
n=60 Participants
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 12 Hours Post-Dose
|
411.39 msec
Standard Error 0.8823
|
410.24 msec
Standard Error 0.8823
|
PRIMARY outcome
Timeframe: 16 hours post-dosePopulation: ECG analysis set included all randomized and treated participants who had at least 1 post-dose ECG measurement in at least 1 period of the crossover.
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The QT interval was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as LS mean difference (CP-690,550 minus Placebo, baseline-adjusted).
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
n=60 Participants
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 16 Hours Post-Dose
|
415.87 msec
Standard Error 0.8823
|
413.72 msec
Standard Error 0.8823
|
PRIMARY outcome
Timeframe: 24 hours post-dosePopulation: ECG analysis set included all randomized and treated participants who had at least 1 post-dose ECG measurement in at least 1 period of the crossover.
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The QT interval was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as LS mean difference (CP-690,550 minus Placebo, baseline-adjusted).
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
n=60 Participants
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 24 Hours Post-Dose
|
412.53 msec
Standard Error 0.8823
|
411.18 msec
Standard Error 0.8823
|
SECONDARY outcome
Timeframe: 2 hours post-dosePopulation: ECG analysis set included all randomized and treated participants who had at least 1 post-dose ECG measurement in at least 1 period of the crossover.
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The QT interval was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as LS mean difference (moxifloxacin minus Placebo, baseline-adjusted).
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
n=60 Participants
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin Compared to Placebo
|
426.34 msec
Standard Error 0.8823
|
415.05 msec
Standard Error 0.8823
|
SECONDARY outcome
Timeframe: 0.25, 0.5, 1, 2, 4, 8, 12, 16, and 24 hours post-dosePopulation: ECG analysis set included all randomized and treated participants who had at least 1 post-dose ECG measurement in at least 1 period of the crossover.
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The QT interval was adjusted for RR interval using the QT and RR from each ECG by Bazett's formula (QTcB = QT divided by square root of RR). Data is reported as LS mean difference (CP-690,550 minus Placebo, baseline-adjusted).
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
n=60 Participants
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo
0.25 Hour Post-Dose
|
416.40 msec
Standard Error 1.1139
|
416.24 msec
Standard Error 1.1139
|
|
Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo
0.5 Hour Post-Dose
|
416.69 msec
Standard Error 1.1139
|
414.91 msec
Standard Error 1.1139
|
|
Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo
1 Hour Post-Dose
|
417.98 msec
Standard Error 1.1139
|
414.99 msec
Standard Error 1.1139
|
|
Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo
2 Hours Post-Dose
|
414.54 msec
Standard Error 1.1139
|
413.46 msec
Standard Error 1.1139
|
|
Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo
4 Hours Post-Dose
|
417.26 msec
Standard Error 1.1139
|
415.10 msec
Standard Error 1.1139
|
|
Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo
8 Hours Post-Dose
|
412.91 msec
Standard Error 1.1139
|
412.86 msec
Standard Error 1.1139
|
|
Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo
12 Hours Post-Dose
|
416.76 msec
Standard Error 1.1139
|
416.27 msec
Standard Error 1.1139
|
|
Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo
16 Hours Post-Dose
|
416.44 msec
Standard Error 1.1139
|
414.33 msec
Standard Error 1.1139
|
|
Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo
24 Hours Post-Dose
|
413.93 msec
Standard Error 1.1139
|
413.14 msec
Standard Error 1.1139
|
SECONDARY outcome
Timeframe: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dosePopulation: Pharmacokinetic (PK) parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for CP-690,550
|
2682.6 nanogram*hour/milliliter (ng*hr/mL)
Standard Deviation 778.15
|
—
|
SECONDARY outcome
Timeframe: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dosePopulation: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for CP-690,550
|
2669.7 ng*hr/mL
Standard Deviation 771.02
|
—
|
SECONDARY outcome
Timeframe: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dosePopulation: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of CP-690,550
|
563.5 nanogram/milliliter (ng/mL)
Standard Deviation 199.23
|
—
|
SECONDARY outcome
Timeframe: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dosePopulation: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) for CP-690,550
|
1.000 hours
Interval 0.3 to 4.08
|
—
|
SECONDARY outcome
Timeframe: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dosePopulation: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
Plasma decay half-life is the time measured for the plasma concentration of drug to decrease by one half.
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Plasma Decay Half-Life (t1/2) of CP-690,550
|
3.284 hours
Standard Deviation 0.4871
|
—
|
SECONDARY outcome
Timeframe: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dosePopulation: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Here 'number analyzed' signifies those participants who were evaluable in each specific category.
AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). Variation in CYP2C19 gene affected the pharmacokinetics of CP-690,550. AUC (0 - ∞) categorized by genotype into poor metabolizer, extensive metabolizer and ultra extensive metabolizer of CYP2C19.
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of CP-690,550 by Cytochrome P450 2C19 (CYP2C19) Genotype
Poor Metabolizer
|
3127.5 ng*hr/mL
Standard Deviation 373.18
|
—
|
|
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of CP-690,550 by Cytochrome P450 2C19 (CYP2C19) Genotype
Extensive Metabolizer
|
2683.5 ng*hr/mL
Standard Deviation 787.75
|
—
|
|
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of CP-690,550 by Cytochrome P450 2C19 (CYP2C19) Genotype
Ultra Extensive Metabolizer
|
1677.7 ng*hr/mL
Standard Deviation 637.68
|
—
|
SECONDARY outcome
Timeframe: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dosePopulation: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Here 'number analyzed' signifies those participants who were evaluable in each specific category.
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Variation in CYP2C19 gene affected the pharmacokinetics of CP-690,550. AUClast categorized by genotype as poor metabolizer, extensive metabolizer and ultra extensive metabolizer of CYP2C19.
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-690,550 by CYP2C19 Genotype
Poor Metabolizer
|
3114.3 ng*hr/mL
Standard Deviation 366.68
|
—
|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-690,550 by CYP2C19 Genotype
Extensive Metabolizer
|
2670.2 ng*hr/mL
Standard Deviation 780.41
|
—
|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-690,550 by CYP2C19 Genotype
Ultra Extensive Metabolizer
|
1673.1 ng*hr/mL
Standard Deviation 636.30
|
—
|
SECONDARY outcome
Timeframe: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dosePopulation: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Here 'number analyzed' signifies those participants who were evaluable in each specific category.
Variation in CYP2C19 gene affected the pharmacokinetics of CP-690,550. Cmax categorized by genotype as poor metabolizer, extensive metabolizer and ultra extensive metabolizer of CYP2C19.
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of CP-690,550 by CYP2C19 Genotype
Poor Metabolizer
|
647.4 ng/mL
Standard Deviation 281.69
|
—
|
|
Maximum Observed Plasma Concentration (Cmax) of CP-690,550 by CYP2C19 Genotype
Extensive Metabolizer
|
565.0 ng/mL
Standard Deviation 185.62
|
—
|
|
Maximum Observed Plasma Concentration (Cmax) of CP-690,550 by CYP2C19 Genotype
Ultra Extensive Metabolizer
|
346.9 ng/mL
Standard Deviation 214.25
|
—
|
SECONDARY outcome
Timeframe: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dosePopulation: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Here 'number analyzed' signifies those participants who were evaluable in each specific category.
Variation in CYP2C19 gene affected the pharmacokinetics of CP-690,550. Tmax categorized by genotype as poor metabolizer, extensive metabolizer and ultra extensive metabolizer of CYP2C19.
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-690,550 by CYP2C19 Genotype
Poor Metabolizer
|
0.500 hours
Interval 0.3 to 4.03
|
—
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-690,550 by CYP2C19 Genotype
Extensive Metabolizer
|
1.000 hours
Interval 0.3 to 4.08
|
—
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-690,550 by CYP2C19 Genotype
Ultra Extensive Metabolizer
|
2.000 hours
Interval 2.0 to 2.0
|
—
|
SECONDARY outcome
Timeframe: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dosePopulation: PK parameter analysis set included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Here 'number analyzed' signifies those participants who were evaluable in each specific category.
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Variation in CYP2C19 gene affected the pharmacokinetics of CP-690,550. t1/2 categorized by genotype as poor metabolizer, extensive metabolizer and ultra extensive metabolizer of CYP2C19.
Outcome measures
| Measure |
CP-690,550 100 mg
n=60 Participants
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
|---|---|---|
|
Plasma Decay Half-Life (t1/2) of CP-690,550 by CYP2C19 Genotype
Poor Metabolizer
|
3.005 hours
Standard Deviation 0.3566
|
—
|
|
Plasma Decay Half-Life (t1/2) of CP-690,550 by CYP2C19 Genotype
Extensive Metabolizer
|
3.320 hours
Standard Deviation 0.5006
|
—
|
|
Plasma Decay Half-Life (t1/2) of CP-690,550 by CYP2C19 Genotype
Ultra Extensive Metabolizer
|
3.201 hours
Standard Deviation 0.1821
|
—
|
Adverse Events
CP-690,550 100 mg
Placebo
Moxifloxacin
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
CP-690,550 100 mg
n=60 participants at risk
Single oral dose of CP-690,550 100 mg (5 x 20 mg tablets) in any intervention period.
|
Placebo
n=60 participants at risk
Single oral dose of placebo matched to CP-690,550 tablets in any intervention period.
|
Moxifloxacin
n=60 participants at risk
Single oral dose of moxifloxacin 400 mg tablet in any intervention period.
|
|---|---|---|---|
|
Cardiac disorders
Palpitations
|
1.7%
1/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
5.0%
3/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Abdominal distension
|
1.7%
1/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Abdominal pain
|
3.3%
2/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
1.7%
1/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Diarrhoea
|
3.3%
2/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
3.3%
2/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Eructation
|
1.7%
1/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Nausea
|
28.3%
17/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Stomach discomfort
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
1.7%
1/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Toothache
|
3.3%
2/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
6/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
1.7%
1/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
1.7%
1/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Infections and infestations
Nasopharyngitis
|
1.7%
1/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Infections and infestations
Oral herpes
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
1.7%
1/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
1.7%
1/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Injury, poisoning and procedural complications
Joint sprain
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
1.7%
1/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
1.7%
1/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Dizziness
|
3.3%
2/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
3.3%
2/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Headache
|
28.3%
17/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
1.7%
1/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
3.3%
2/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Syncope vasovagal
|
1.7%
1/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.7%
1/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
1.7%
1/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
0.00%
0/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
1.7%
1/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
1.7%
1/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
3.3%
2/60
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant , or one participant may have experienced both a serious and nonserious event during the study.
|
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