Improved disease activity with fosdagrocorat (PF-04171327), a partial agonist of the glucocorticoid receptor, in patients with rheumatoid arthritis: a Phase 2 randomized study.
OBJECTIVE
To assess efficacy and safety of fosdagrocorat (PF-04171327), a potential dissociated agonist of the glucocorticoid receptor, in rheumatoid arthritis (RA) patients.


METHODS
This multicenter, double-blind, parallel-group, active- and placebo-controlled Phase 2 study (NCT00938587) randomized 86 patients (1 : 1 : 1 : 1) to receive fosdagrocorat 10 mg, fosdagrocorat 25 mg, prednisone 5 mg or placebo, all with stable background methotrexate therapy. The primary outcome was change from baseline in Disease Activity Score of 28 joints (DAS28-4[C-reactive protein (CRP)]) after 2 weeks of treatment. Secondary outcomes included American College of Rheumatology (ACR) response rates, change from baseline in ACR core components and Health Assessment Questionnaire Disability Index.


RESULTS
At week 2, improvements from baseline in DAS28-4(CRP) with fosdagrocorat 10 and 25 mg, prednisone 5 mg and placebo were -1.69, -2.22, -1.17 and -0.96, respectively, and were statistically significantly greater for both fosdagrocorat doses versus placebo (P < 0.05) and for fosdagrocorat 25 mg versus prednisone 5 mg (P < 0.001). The effects of fosdagrocorat on secondary outcomes were generally consistent with those observed for the primary outcome. Adverse events (AEs) were reported for eight (38%), three (14%), four (19%) and 12 (55%) patients treated with fosdagrocorat 10 and 25 mg, prednisone 5 mg and placebo, respectively. Most AEs were mild in severity. Four patients discontinued treatment due to AEs (fosdagrocorat 10 mg, n = 2; placebo, n = 2). There were no serious AEs.


CONCLUSIONS
Fosdagrocorat 10 and 25 mg demonstrated efficacy in improving signs and symptoms in RA patients, with manageable AEs. Additional studies are needed to assess the longer-term safety and efficacy of fosdagrocorat.
Pfizer Inc, Collegeville, Pennsylvania, USA.
Thomas
T
Stock
Pfizer Inc, Groton, Connecticut, USA.
Dona
D
Fleishaker
Pfizer Inc, Groton, Connecticut, USA.
Xin
X
Wang
Pfizer Inc, Groton, Connecticut, USA.
Arnab
A
Mukherjee
Pfizer Inc, Groton, Connecticut, USA.
Charles
C
Mebus
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D004185:Disability Evaluation; D004311:Double-Blind Method; D054333:Drug Partial Agonism; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007596:Joints / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D010755:Organophosphates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D010616:Phenanthrenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011241:Prednisone / Q000008:administration & dosage; D011965:Receptors, Glucocorticoid / Q000819:agonists* / Q000378:metabolism; D020127:Recovery of Function; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D001549:Benzamides
D018501:Antirheumatic Agents; D015415:Biomarkers; D002097:C-Reactive Protein; D005938:Glucocorticoids; D006854:Hydrocortisone; D008727:Methotrexate; D010755:Organophosphates; D010616:Phenanthrenes; D011241:Prednisone; D011965:Receptors, Glucocorticoid; C000615597:fosdagrocorat; D001549:Benzamides
arthritis; glucocorticoids; prednisone; randomized controlled trial; rheumatoid