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CP-690,550 Thorough QTc Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
Information provided by (Responsible Party):
Pfizer

Study Description
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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.

Condition or disease Intervention/treatment Phase
Healthy Drug: CP-690,550 Drug: Placebo Drug: Moxifloxacin Phase 1

Detailed Description:
The current study is designed to ascertain whether CP-690,550 is associated with QTc prolongation
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
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
Actual Study Start Date : October 26, 2007
Actual Primary Completion Date : February 7, 2008
Actual Study Completion Date : February 9, 2008

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Arms and Interventions
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Arm Intervention/treatment
Experimental: CP-690,550 100 mg Drug: CP-690,550
Single dose 100 mg (5 x 20 mg tablets)
Placebo Comparator: Placebo Drug: Placebo
Single dose placebo tablets (5 tablets)
Active Comparator: Moxifloxacin hydrochloride Drug: Moxifloxacin
Single dose Avelox 400 mg tablet


Outcome Measures
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Primary Outcome Measures :
  1. 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).

  2. 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).

  3. 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).

  4. 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).

  5. 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).

  6. 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).

  7. 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).

  8. 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).

  9. 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).


Secondary Outcome Measures :
  1. 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).

  2. 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).

  3. 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 - ∞).

  4. 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).

  5. 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 ]
  6. 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 ]
  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01743677


Locations
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Belgium
Pfizer Clinical Research Unit
Bruxelles, Belgium, 1070
Singapore
Pfizer Clinical Research Unit
Singapore, Singapore, 188770
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
More Information
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Additional Information:

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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01743677    
Other Study ID Numbers: A3921028
2007-004492-19 ( EudraCT Number )
First Posted: December 6, 2012    Key Record Dates
Results First Posted: September 16, 2020
Last Update Posted: September 16, 2020
Last Verified: August 2020
Individual Participant Data (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.
Keywords provided by Pfizer:
TQT study
CP-690
550
Additional relevant MeSH terms:
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Moxifloxacin
Tofacitinib
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
 Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Kinase Inhibitors