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Trial record 1 of 1 for:    NCT00838565
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Phase I Study Of The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Intravenously Administered Doses Of PF-04236921 In Patients With Rheumatoid Arthritis

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ClinicalTrials.gov Identifier: NCT00838565
Recruitment Status : Completed
First Posted : February 6, 2009
Results First Posted : November 2, 2018
Last Update Posted : November 2, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE February 4, 2009
First Posted Date  ICMJE February 6, 2009
Results First Submitted Date  ICMJE August 8, 2017
Results First Posted Date  ICMJE November 2, 2018
Last Update Posted Date November 2, 2018
Actual Study Start Date  ICMJE May 20, 2009
Actual Primary Completion Date February 2, 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 12, 2018)
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 28 days after last dose of study medication or until serum PF-04236921 concentrations below the LLOQ (up to Day 624) ]
    An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study medication and up to 28 days after last dose or until serum PF-04236921 concentrations were below the LLOQ that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events.
  • Number of Participants With Positive Anti-drug Antibodies Response [ Time Frame: Day 1, 28, 56, 84, 174, 354, End of Study (Day 624) ]
  • Maximum Observed Serum Concentration (Cmax): Day 1 [ Time Frame: Day 1: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose ]
  • Time to Reach Maximum Observed Serum Concentration (Tmax): Day 1 [ Time Frame: Day 1: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 1 [ Time Frame: Day 1: Pre-dose (0 hour), 15 minutes, 168 hours post-dose ]
    AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168).
  • Maximum Observed Serum Concentration (Cmax): Day 28 [ Time Frame: Day 28: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose ]
  • Time to Reach Maximum Observed Serum Concentration (Tmax): Day 28 [ Time Frame: Day 28: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 28 [ Time Frame: Day 28: Pre-dose (0 hour), 15 minutes, 168 hours post-dose ]
    AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168).
  • Maximum Observed Serum Concentration (Cmax): Day 56 [ Time Frame: Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose ]
  • Time to Reach Maximum Observed Serum Concentration (Tmax): Day 56 [ Time Frame: Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 56 [ Time Frame: Day 56: Pre-dose (0 hour), 15 minutes, 168 hours post-dose ]
    AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168).
  • Serum Decay Half-Life (t1/2): Day 56 [ Time Frame: Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose ]
    Serum decay half-life is the time measured for the serum concentration to decrease by one half.
Original Primary Outcome Measures  ICMJE
 (submitted: February 4, 2009)
  • Safety/Tolerability of Multiple Intravenously Administered Doses of PF-04236921 [ Time Frame: 2 years ]
  • Pharmacokinetics of PF-04236921 after Multiple Intravenously-Administered Doses [ Time Frame: 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: February 4, 2009)
Pharmacodynamics of PF-04236921 after Multiple Intravenously-Administered Doses [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures
 (submitted: March 12, 2018)
  • Change From Baseline in C-Reactive Protein (CRP) Concentrations at Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624 and Early Discontinuation [ Time Frame: Baseline, Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624, Early Discontinuation ]
    The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultra sensitive assay. A decrease in the level of CRP indicates reduction in inflammation.
  • Change From Baseline in Log CRP Concentrations at Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624 [ Time Frame: Baseline, Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624 ]
    The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.
  • Change From Baseline in Absolute Neutrophil Counts at Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624 and Early Discontinuation [ Time Frame: Baseline, Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624, Early Discontinuation ]
  • Change From Baseline in Free Interleukin-6 (IL-6) Concentrations at Day 28, 56, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579 and 624 [ Time Frame: Baseline, Day 28, 56, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624 ]
    Serum samples were analyzed for IL-6 concentrations using a validated analytical colorimetric Enzyme-Linked Immunosorbent Assay (ELISA) method.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I Study Of The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Intravenously Administered Doses Of PF-04236921 In Patients With Rheumatoid Arthritis
Official Title  ICMJE Phase 1, Randomized, Patient And Investigator-blind, Placebo-controlled Study To Investigate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Intravenously Administered Doses Of Pf-04236921 In Patients With Rheumatoid Arthritis Receiving Methotrexate
Brief Summary This study will evaluate the safety and tolerability of PF-04236921 administered monthly as three intravenous infusions. Each group of patients will be assigned to a dose level; Safety and tolerability of a low dose level will be required before proceeding to successively higher dose levels. Blood tests will be performed to measure the amount of drug and changes in measures of inflammation.
Detailed Description Safety and Tolerability and Pharmacokinetic/Pharmacodynamic assessment of inflammation-related biomarkers.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Drug: Placebo
    intravenous infusion on three consecutive months
  • Drug: dose level 1
    intravenous infusion on three consecutive months
  • Drug: dose level 2
    intravenous infusion on three consecutive months
  • Drug: dose level 3
    intravenous infusion on three consecutive months
  • Drug: dose level 4
    intravenous infusion on 3 consecutive months
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
  • Experimental: PF-04236921
    Interventions:
    • Drug: dose level 1
    • Drug: dose level 2
    • Drug: dose level 3
    • Drug: dose level 4
Publications * Li C, Shoji S, Beebe J. Pharmacokinetics and C-reactive protein modelling of anti-interleukin-6 antibody (PF-04236921) in healthy volunteers and patients with autoimmune disease. Br J Clin Pharmacol. 2018 Sep;84(9):2059-2074. doi: 10.1111/bcp.13641. Epub 2018 Jun 25.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 28, 2012)
41
Original Estimated Enrollment  ICMJE
 (submitted: February 4, 2009)
40
Actual Study Completion Date  ICMJE February 2, 2012
Actual Primary Completion Date February 2, 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Rheumatoid Arthritis on a stable dose of methotrexate
  • Rheumatoid Arthritis disease activity as assessed by blood tests

Exclusion Criteria:

  • Serious or uncontrolled medical conditions
  • Current or recent treatment with disease-modifying drugs other than methotrexate including but not limited to leflunomide, sulfasalazine, etanercept, infliximab, adalimumab, abatacept, rituximab
  • Current oral glucocorticoid dose of more than 10 mg/d prednisone equivalent
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00838565
Other Study ID Numbers  ICMJE B0151002
2009-009866-15 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP