Healthy
Conditions
Keywords
TQT study, CP-690, 550
Brief summary
ICH E14 recommends that a thorough QT/QTc (TQT) study should be performed to determine whether intensive monitoring of QT interval in target patient populations is required during later stages of development. The current study is designed to ascertain whether CP-690,550 is associated with QTc prolongation.
Detailed description
The current study is designed to ascertain whether CP-690,550 is associated with QTc prolongation
Interventions
DRUGCP-690,550
Single dose 100 mg (5 x 20 mg tablets)
DRUGPlacebo
Single dose placebo tablets (5 tablets)
DRUGMoxifloxacin
Single dose Avelox 400 mg tablet
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and/or female subjects between ages of 18 and 55 years, inclusive. * Body Mass Index (BMI) of approximately 18 to 30 kg/m2; and a total body weight \>50 kg (110 lbs).
Exclusion criteria
* Use of tobacco- or nicotine-containing products in excess of equivalent of 5 cigarettes per day. * 12-lead ECG demonstrating QTc \>450 msec or other clinically significant abnormalities at Screening. * History of risk factors for QT prolongation or torsades de pointes. * Pregnant or nursing women; women of childbearing potential unwilling or unable to use an acceptable method of nonhormonal contraception from at least 14 days prior to first dose until completion of follow-up. * Use of prescription or nonprescription drugs, vitamins and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to first dose of trial medication. * Any clinically significant infections within past 3 months or evidence of infection in past 7 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 8 Hours Post-Dose | 8 hours post-dose | 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). |
| Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 0.25 Hour Post-Dose | 0.25 hour post-dose | 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). |
| Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 0.5 Hour Post-Dose | 0.5 hour post-dose | 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). |
| Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 1 Hour Post-Dose | 1 hour post-dose | 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). |
| Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 2 Hours Post-Dose | 2 hours post-dose | 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). |
| Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 4 Hours Post-Dose | 4 hours post-dose | 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). |
| Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 12 Hours Post-Dose | 12 hours post-dose | 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). |
| Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 16 Hours Post-Dose | 16 hours post-dose | 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). |
| Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 24 Hours Post-Dose | 24 hours post-dose | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of CP-690,550 by CYP2C19 Genotype | 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose | 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. |
| Maximum Observed Plasma Concentration (Cmax) of CP-690,550 | 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose | — |
| Plasma Decay Half-Life (t1/2) of CP-690,550 by CYP2C19 Genotype | 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose | 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. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-690,550 by CYP2C19 Genotype | 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose | 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. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for CP-690,550 | 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose | — |
| Plasma Decay Half-Life (t1/2) of CP-690,550 | 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose | Plasma decay half-life is the time measured for the plasma concentration of drug to decrease by one half. |
| Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin Compared to Placebo | 2 hours post-dose | 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). |
| Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo | 0.25, 0.5, 1, 2, 4, 8, 12, 16, and 24 hours post-dose | 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). |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for CP-690,550 | 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose | 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 - ∞). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for CP-690,550 | 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of CP-690,550 by Cytochrome P450 2C19 (CYP2C19) Genotype | 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose | 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. |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-690,550 by CYP2C19 Genotype | 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose | 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. |
Countries
Belgium, Singapore
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes participants randomized to receive any treatment (CP-690,550 100 mg first, moxifloxacin 400 mg first, or placebo first). | 60 |
| Total | 60 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 32.7 years STANDARD_DEVIATION 9.2 |
| Sex: Female, Male Female | 28 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 32 / 60 | 6 / 60 | 10 / 60 |
| serious Total, serious adverse events | 0 / 60 | 0 / 60 | 0 / 60 |
Outcome results
Primary
Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 0.25 Hour Post-Dose
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).
Time frame: 0.25 hour post-dose
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 100 mg | 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 |
| Placebo | Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 0.25 Hour Post-Dose | 417.77 milliseconds (msec) | Standard Error 0.8823 |
90% CI: [-3.15, 0.56]
Primary
Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 0.5 Hour Post-Dose
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).
Time frame: 0.5 hour post-dose
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 100 mg | 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 |
| Placebo | Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 0.5 Hour Post-Dose | 416.12 msec | Standard Error 0.8823 |
90% CI: [-3.28, 0.43]
Primary
Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 12 Hours Post-Dose
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).
Time frame: 12 hours post-dose
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 100 mg | 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 |
| Placebo | Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 12 Hours Post-Dose | 410.24 msec | Standard Error 0.8823 |
90% CI: [-0.71, 3]
Primary
Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 16 Hours Post-Dose
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).
Time frame: 16 hours post-dose
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 100 mg | 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 |
| Placebo | Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 16 Hours Post-Dose | 413.72 msec | Standard Error 0.8823 |
90% CI: [0.29, 4]
Primary
Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 1 Hour Post-Dose
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).
Time frame: 1 hour post-dose
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 100 mg | 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 |
| Placebo | Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 1 Hour Post-Dose | 416.98 msec | Standard Error 0.8823 |
90% CI: [-4.15, -0.44]
Primary
Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 24 Hours Post-Dose
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).
Time frame: 24 hours post-dose
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 100 mg | 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 |
| Placebo | Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 24 Hours Post-Dose | 411.18 msec | Standard Error 0.8823 |
90% CI: [-0.5, 3.21]
Primary
Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 2 Hours Post-Dose
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).
Time frame: 2 hours post-dose
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 100 mg | 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 |
| Placebo | Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 2 Hours Post-Dose | 415.05 msec | Standard Error 0.8823 |
90% CI: [-3.21, 0.5]
Primary
Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 4 Hours Post-Dose
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).
Time frame: 4 hours post-dose
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 100 mg | 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 |
| Placebo | Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 4 Hours Post-Dose | 415.76 msec | Standard Error 0.8823 |
90% CI: [-0.78, 2.93]
Primary
Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 8 Hours Post-Dose
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).
Time frame: 8 hours post-dose
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 100 mg | 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 |
| Placebo | Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 8 Hours Post-Dose | 408.39 msec | Standard Error 0.8823 |
90% CI: [-1, 2.71]
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for CP-690,550
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 - ∞).
Time frame: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 100 mg | 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
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of CP-690,550 by Cytochrome P450 2C19 (CYP2C19) Genotype
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.
Time frame: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CP-690,550 100 mg | 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 |
| CP-690,550 100 mg | 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 |
| CP-690,550 100 mg | 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 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for CP-690,550
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Time frame: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 100 mg | 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
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-690,550 by CYP2C19 Genotype
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.
Time frame: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CP-690,550 100 mg | 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 636.3 |
| CP-690,550 100 mg | 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 |
| CP-690,550 100 mg | 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 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of CP-690,550
Time frame: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 100 mg | Maximum Observed Plasma Concentration (Cmax) of CP-690,550 | 563.5 nanogram/milliliter (ng/mL) | Standard Deviation 199.23 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of CP-690,550 by CYP2C19 Genotype
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.
Time frame: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CP-690,550 100 mg | Maximum Observed Plasma Concentration (Cmax) of CP-690,550 by CYP2C19 Genotype | Poor Metabolizer | 647.4 ng/mL | Standard Deviation 281.69 |
| CP-690,550 100 mg | Maximum Observed Plasma Concentration (Cmax) of CP-690,550 by CYP2C19 Genotype | Extensive Metabolizer | 565.0 ng/mL | Standard Deviation 185.62 |
| CP-690,550 100 mg | Maximum Observed Plasma Concentration (Cmax) of CP-690,550 by CYP2C19 Genotype | Ultra Extensive Metabolizer | 346.9 ng/mL | Standard Deviation 214.25 |
Secondary
Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo
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).
Time frame: 0.25, 0.5, 1, 2, 4, 8, 12, 16, and 24 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| CP-690,550 100 mg | 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 |
| CP-690,550 100 mg | 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 |
| CP-690,550 100 mg | 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 |
| CP-690,550 100 mg | 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 |
| CP-690,550 100 mg | 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 |
| CP-690,550 100 mg | 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 |
| CP-690,550 100 mg | 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 |
| CP-690,550 100 mg | 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 |
| CP-690,550 100 mg | 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 |
| Placebo | Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo | 24 Hours Post-Dose | 413.14 msec | Standard Error 1.1139 |
| Placebo | Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo | 1 Hour Post-Dose | 414.99 msec | Standard Error 1.1139 |
| Placebo | Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo | 8 Hours Post-Dose | 412.86 msec | Standard Error 1.1139 |
| Placebo | Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo | 0.5 Hour Post-Dose | 414.91 msec | Standard Error 1.1139 |
| Placebo | Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo | 2 Hours Post-Dose | 413.46 msec | Standard Error 1.1139 |
| Placebo | Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo | 4 Hours Post-Dose | 415.10 msec | Standard Error 1.1139 |
| Placebo | Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo | 12 Hours Post-Dose | 416.27 msec | Standard Error 1.1139 |
| Placebo | Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo | 16 Hours Post-Dose | 414.33 msec | Standard Error 1.1139 |
| Placebo | Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo | 0.25 Hour Post-Dose | 416.24 msec | Standard Error 1.1139 |
Comparison: 0.25 hour post-dose90% CI: [-2.11, 2.44]
Comparison: 0.5 hour post-dose90% CI: [-0.49, 4.06]
Comparison: 1 hour post-dose90% CI: [0.71, 5.26]
Comparison: 2 hours post-dose90% CI: [-1.19, 3.36]
Comparison: 4 hours post-dose90% CI: [-0.11, 4.44]
Comparison: 8 hours post-dose90% CI: [-2.22, 2.33]
Comparison: 12 hours post-dose90% CI: [-1.79, 2.76]
Comparison: 16 hours post-dose90% CI: [-0.17, 4.38]
Comparison: 24 hours post-dose90% CI: [-1.49, 3.06]
Secondary
Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin Compared to Placebo
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).
Time frame: 2 hours post-dose
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 100 mg | Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin Compared to Placebo | 426.34 msec | Standard Error 0.8823 |
| Placebo | Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin Compared to Placebo | 415.05 msec | Standard Error 0.8823 |
90% CI: [9.62, 12.96]
Secondary
Plasma Decay Half-Life (t1/2) of CP-690,550
Plasma decay half-life is the time measured for the plasma concentration of drug to decrease by one half.
Time frame: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-690,550 100 mg | Plasma Decay Half-Life (t1/2) of CP-690,550 | 3.284 hours | Standard Deviation 0.4871 |
Secondary
Plasma Decay Half-Life (t1/2) of CP-690,550 by CYP2C19 Genotype
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.
Time frame: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CP-690,550 100 mg | Plasma Decay Half-Life (t1/2) of CP-690,550 by CYP2C19 Genotype | Poor Metabolizer | 3.005 hours | Standard Deviation 0.3566 |
| CP-690,550 100 mg | Plasma Decay Half-Life (t1/2) of CP-690,550 by CYP2C19 Genotype | Extensive Metabolizer | 3.320 hours | Standard Deviation 0.5006 |
| CP-690,550 100 mg | Plasma Decay Half-Life (t1/2) of CP-690,550 by CYP2C19 Genotype | Ultra Extensive Metabolizer | 3.201 hours | Standard Deviation 0.1821 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) for CP-690,550
Time frame: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CP-690,550 100 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) for CP-690,550 | 1.000 hours |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-690,550 by CYP2C19 Genotype
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.
Time frame: 0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CP-690,550 100 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-690,550 by CYP2C19 Genotype | Ultra Extensive Metabolizer | 2.000 hours |
| CP-690,550 100 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-690,550 by CYP2C19 Genotype | Poor Metabolizer | 0.500 hours |
| CP-690,550 100 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-690,550 by CYP2C19 Genotype | Extensive Metabolizer | 1.000 hours |