CP-690,550 Thorough QTc Study

• ClinicalTrials.gov Identifier: NCT01743677
• Recruitment Status: Completed
• First Posted: December 6, 2012
• Results First Posted: September 16, 2020
• Last Update Posted: September 16, 2020
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: October 25, 2012
• First Posted Date: December 6, 2012
• Results First Submitted Date: December 6, 2012
• Results First Posted Date: September 16, 2020
• Last Update Posted Date: September 16, 2020
• Actual Study Start Date: October 26, 2007
• Actual Primary Completion Date: February 7, 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 27, 2020)

• Mean Time-Matched Difference in QTcF Intervals Between CP-690,550 Compared to Placebo at 0.25 Hour Post-Dose [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 8 Hours Post-Dose [ Time Frame: 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 12 Hours Post-Dose [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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).

Original Primary Outcome Measures (submitted: December 4, 2012)

• Time-matched mean differences in QTcF intervals between CP-690,550 and placebo (baseline-adjusted) at each postdose time [ Time Frame: 0.25 hr postdose ]
• Time-matched mean differences in QTcF intervals between CP-690,550 and placebo (baseline-adjusted) at each postdose time [ Time Frame: 0.5 hr postdose ]
• Time-matched mean differences in QTcF intervals between CP-690,550 and placebo (baseline-adjusted) at each postdose time [ Time Frame: 1 hr postdose ]
• Time-matched mean differences in QTcF intervals between CP-690,550 and placebo (baseline-adjusted) at each postdose time [ Time Frame: 2 hr postdose ]
• Time-matched mean differences in QTcF intervals between CP-690,550 and placebo (baseline-adjusted) at each postdose time [ Time Frame: 4 hr postdose ]
• Time-matched mean differences in QTcF intervals between CP-690,550 and placebo (baseline-adjusted) at each postdose time [ Time Frame: 8 hr postdose ]
• Time-matched mean differences in QTcF intervals between CP-690,550 and placebo (baseline-adjusted) at each postdose time [ Time Frame: 12 hr postdose ]
• Time-matched mean differences in QTcF intervals between CP-690,550 and placebo (baseline-adjusted) at each postdose time [ Time Frame: 16 hr postdose ]
• Time-matched mean differences in QTcF intervals between CP-690,550 and placebo (baseline-adjusted) at each postdose time [ Time Frame: 24 hr postdose ]

Current Secondary Outcome Measures (submitted: August 27, 2020)

• Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin Compared to Placebo [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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).
• 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 ]
• 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 ]
• Plasma Decay Half-Life (t1/2) 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 ]
  Plasma decay half-life is the time measured for the plasma concentration of drug to decrease by one half.
• Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of CP-690,550 by Cytochrome P450 2C19 (CYP2C19) Genotype [ Time Frame: 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 [ Time Frame: 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.
• Maximum Observed Plasma Concentration (Cmax) of CP-690,550 by CYP2C19 Genotype [ Time Frame: 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.
• Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-690,550 by CYP2C19 Genotype [ Time Frame: 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.
• Plasma Decay Half-Life (t1/2) of CP-690,550 by CYP2C19 Genotype [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: December 4, 2012)

• Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin Compared to Placebo [ Time Frame: -1, -0.5, and 0 hrs predose and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hr postdose ]
• Mean Time-Matched Difference in QTcB Intervals Between CP-690,550 Compared to Placebo [ Time Frame: -1, -0.5, and 0 hrs predose and 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hr postdose ]
• Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC(0-infinity)] [ Time Frame: predose, 0.25,0.5,1,2,4,8,12,16 and 24 hr postdose ]
• Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUClast) [ Time Frame: predose, 0.25,0.5,1,2,4,8,12,16 and 24 hr postdose ]
• Maximum Observed Plasma Concentration (Cmax) [ Time Frame: predose, 0.25,0.5,1,2,4,8,12,16 and 24 hr postdose ]
• Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: predose, 0.25,0.5,1,2,4,8,12,16 and 24 hr postdose ]
• Plasma Decay Half-Life (t1/2) [ Time Frame: predose, 0.25,0.5,1,2,4,8,12,16 and 24 hr postdose ]
• Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC(0-infinity)] by CYP2C19 Genotype [ Time Frame: predose, 0.25,0.5,1,2,4,8,12,16 and 24 hr postdose ]
• Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) by CYP2C19 Genotype [ Time Frame: predose, 0.25,0.5,1,2,4,8,12,16 and 24 hr postdose ]
• Maximum Observed Plasma Concentration (Cmax) by CYP2C19 Genotype [ Time Frame: predose, 0.25,0.5,1,2,4,8,12,16 and 24 hr postdose ]
• Time to Reach Maximum Observed Plasma Concentration (Tmax) by CYP2C19 Genotype [ Time Frame: predose, 0.25,0.5,1,2,4,8,12,16 and 24 hr postdose ]
• Plasma Decay Half-Life (t1/2) by CYP2C19 Genotype [ Time Frame: predose, 0.25,0.5,1,2,4,8,12,16 and 24 hr postdose ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: CP-690,550 Thorough QTc Study
• 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
• 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
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Other
• Condition: Healthy

Intervention

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

Study Arms

• Experimental: CP-690,550 100 mg
  Intervention: Drug: CP-690,550
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo
• Active Comparator: Moxifloxacin hydrochloride
  Intervention: Drug: Moxifloxacin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 4, 2012): 60
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: February 9, 2008
• Actual Primary Completion Date: February 7, 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Singapore

Administrative Information

• NCT Number: NCT01743677
• Other Study ID Numbers: A3921028; 2007-004492-19 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: August 2020