Phase I Study Of The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Intravenously Administered Doses Of PF-04236921 In Patients With Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00838565
• Other study ID #: B0151002
• Secondary ID: 2009-009866-15
• Status: Completed
• Phase: Phase 1
• Start date: May 20, 2009
• Est. completion date: February 2, 2012

Study information

• Verified date: March 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Safety and Tolerability and Pharmacokinetic/Pharmacodynamic assessment of inflammation-related biomarkers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: February 2, 2012
• Est. primary completion date: February 2, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Placebo
intravenous infusion on three consecutive months
• dose level 1
intravenous infusion on three consecutive months
• dose level 2
intravenous infusion on three consecutive months
• dose level 3
intravenous infusion on three consecutive months
• dose level 4
intravenous infusion on 3 consecutive months

Locations

Country	Name	City	State
Korea, Republic of	Inha University Hospital, Medicine/Rheumatology	Incheon
Korea, Republic of	Seoul National University Hospital, Rheumatology, Internal Medicine	Seoul
Korea, Republic of	Yonsei University College of Medicine, Severance Hospital, Clinical Trial Center	Seoul
Spain	Complexo Hospitalario Universitario A Coruña	A Coruña
Spain	Hospital Clinico Universitario de Santiago	Santiago de Compostela	A Coruña
United States	Allergy, Asthma, Arthritis, & Lung	Daytona Beach	Florida
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Millennium Research	Ormond Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	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.	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
Other	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	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.	Baseline, Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624
Other	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		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
Other	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	Serum samples were analyzed for IL-6 concentrations using a validated analytical colorimetric Enzyme-Linked Immunosorbent Assay (ELISA) method.	Baseline, Day 28, 56, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624
Primary	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	Baseline up to 28 days after last dose of study medication or until serum PF-04236921 concentrations below the LLOQ (up to Day 624)
Primary	Number of Participants With Positive Anti-drug Antibodies Response		Day 1, 28, 56, 84, 174, 354, End of Study (Day 624)
Primary	Maximum Observed Serum Concentration (Cmax): Day 1		Day 1: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose
Primary	Time to Reach Maximum Observed Serum Concentration (Tmax): Day 1		Day 1: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose
Primary	Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 1	AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168).	Day 1: Pre-dose (0 hour), 15 minutes, 168 hours post-dose
Primary	Maximum Observed Serum Concentration (Cmax): Day 28		Day 28: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose
Primary	Time to Reach Maximum Observed Serum Concentration (Tmax): Day 28		Day 28: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose
Primary	Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 28	AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168).	Day 28: Pre-dose (0 hour), 15 minutes, 168 hours post-dose
Primary	Maximum Observed Serum Concentration (Cmax): Day 56		Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose
Primary	Time to Reach Maximum Observed Serum Concentration (Tmax): Day 56		Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose
Primary	Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 56	AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168).	Day 56: Pre-dose (0 hour), 15 minutes, 168 hours post-dose
Primary	Serum Decay Half-Life (t1/2): Day 56	Serum decay half-life is the time measured for the serum concentration to decrease by one half.	Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose

External Links

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