A proof-of-concept and drug-drug interaction study of pamapimod, a novel p38 MAP kinase inhibitor, with methotrexate in patients with rheumatoid arthritis.

This study evaluated the potential pharmacokinetic interaction of pamapimod, a p38 mitogen-activated protein kinase inhibitor, and methotrexate (MTX) when administered concomitantly in patients with rheumatoid arthritis (RA); the study also evaluated the pharmacodynamic effects of pamapimod. Twenty-two RA patients on a stable regimen of MTX (10-25 mg/wk; administered on days 1 and 8) were randomized to receive 300 mg of pamapimod (n = 17) or placebo (n = 5) once daily (qd) for 10 days (days 5-14). Blood and urine samples were collected pre- and postdose on days 1 (MTX alone), 7 (pamapimod alone), and 8 (MTX and pamapimod coadministered).

A longitudinal study of gene expression in healthy individuals.

Background: The use of gene expression in venous blood either as a pharmacodynamic marker in clinical trials of drugs or as a diagnostic test requires knowledge of the variability in expression over time in healthy volunteers. Here we defined a normal range of gene expression over 6 months in the blood of four cohorts of healthy men and women who were stratified by age (22-55 years and > 55 years) and gender.

Methods: Eleven immunomodulatory genes likely to play important roles in inflammatory conditions such as rheumatoid arthritis and infection in addition to four genes typically used as reference genes were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), as well as the full genome as represented by Affymetrix HG U133 Plus 2.

Period correction of the QTc of moxifloxacin with multiple predose baseline ECGs is the least variable of 4 methods tested.

This study compares 4 baseline correction methods on the effect of moxifloxacin on the QT/QTc interval: (1) day -1 time-matched baseline electrocardiograms (ECGs), (2) 3 triplicate predose ECGs, (3) 1 triplicate predose ECG, and (4) no baseline correction. Forty-four healthy subjects receive a single dose of moxifloxacin (400 mg), placebo, and 2 doses of an investigational agent in a 4-period crossover fashion. For all 4 methods, the largest mean difference from placebo in the moxifloxacin study-specific QTc is 11.

Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor, in a double-blind, methotrexate-controlled study of patients with active rheumatoid arthritis.

Objective: To determine the efficacy and safety of pamapimod (a selective inhibitor of the alpha-isoform of p38 MAP kinase) as monotherapy in comparison with methotrexate (MTX) treatment in adult patients with active rheumatoid arthritis (RA).

Methods: Patients were randomly assigned to 1 of 4 treatment groups and received 12 weeks of double-blind treatment. One group received MTX (7.