CP-690,550 Thorough QTc Study

Healthy Clinical Trial

Official title:

A PHASE 1, RANDOMIZED, PLACEBO- AND POSITIVE-CONTROLLED CROSS-OVER STUDY TO DETERMINE THE EFFECT OF SINGLE-DOSE CP-690,550 ON QTC INTERVAL IN HEALTHY VOLUNTEERS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01743677
• Other study ID #: A3921028
• Secondary ID: 2007-004492-19
• Status: Completed
• Phase: Phase 1
• Start date: October 26, 2007
• Est. completion date: February 9, 2008

Study information

• Verified date: August 2020
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The current study is designed to ascertain whether CP-690,550 is associated with QTc prolongation

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: February 9, 2008
• Est. primary completion date: February 7, 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• CP-690,550
Single dose 100 mg (5 x 20 mg tablets)
• Placebo
Single dose placebo tablets (5 tablets)
• Moxifloxacin
Single dose Avelox 400 mg tablet

Locations

Country	Name	City	State
Belgium	Pfizer Clinical Research Unit	Bruxelles
Singapore	Pfizer Clinical Research Unit	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

Belgium,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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).	0.25 hour post-dose
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).	0.5 hour post-dose
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).	1 hour post-dose
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).	2 hours post-dose
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).	4 hours post-dose
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).	8 hours post-dose
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).	12 hours post-dose
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).	16 hours post-dose
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).	24 hours post-dose
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).	2 hours post-dose
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).	0.25, 0.5, 1, 2, 4, 8, 12, 16, and 24 hours post-dose
Secondary	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] for CP-690,550	AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).	0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose
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).	0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose
Secondary	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
Secondary	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
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.	0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose
Secondary	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] of CP-690,550 by Cytochrome P450 2C19 (CYP2C19) Genotype	AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8). Variation in CYP2C19 gene affected the pharmacokinetics of CP-690,550. AUC (0 - 8) categorized by genotype into poor metabolizer, extensive metabolizer and ultra extensive metabolizer of CYP2C19.	0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose
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.	0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose
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.	0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose
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.	0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose
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.	0 (pre-dose), and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours post-dose

External Links

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