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Merck Poster 800x500_2007-7 17.10.2007 16:49 Uhr Seite 1 New Modified-Release (MR) Prednisone Tablet Shows Sustained Reduction
of Morning Stiffness and Interleukin-6 (IL-6) in Patients with Rheumatoid
Arthritis (RA).
Frank Buttgereit1, Gisela Doering2, Achim Schaeffler3, Stephan Witte3, Jacek Szechinski4, Rieke Alten5.
1Charité University Hospital, CCM, Berlin, Germany; 2Merck KGaA, Darmstadt, Germany; 3Nitec Pharma AG, Reinach, Switzerland;
4Med. Univ. Dept. of Rheumatology, Wroclaw, Poland; 5Dept. Int. Med. II, Rheumatology Schlosspark-Klinik, Berlin, Germany
STATEMENT OF PURPOSE Glucocorticoids (GCs) are efficient drugs for the treatment of
Phase III Study:
Phase III Study:
rheumatic diseases, for short-term treatments as well as to control symptoms of RA over Number of Patients
time, due to their anti-inflammatory and immunosuppressive effects. However, side effects limit their use. Optimization is therefore needed and several new chemical entities are indevelopment. Approaches for optimizing conventional GCs include new delivery systems to adapt drug release to the circadian rhythms of endogenous cortisol and RA symptoms, which are typically most active during the early morning hours. A MR tablet has recently been developed that releases prednisone 4 hours after ingestion. If taken at bedtime, drug release occurs during the night. This MR tablet has been investigated in a controlled clinical study in 288 patients with RA who were pre-treated with GCs and DMARDs METHODS During the initial 3-month double-blind treatment phase, the MR tablet was
compared to immediate release (IR) prednisone. Individual doses (3-10 mg/day) were iden- Phase III Study:
tical or equivalent to pre-study doses. During the subsequent 9-month open-label exten- Phase III Study:
Open Follow-up
Open Follow-up
sion all patients received MR prednisone. The primary outcome measure was duration of morning stiffness recorded in diaries. Secondary endpoints included IL-6 as marker of inflammation as well as RA status and general safety.
RESULTS 288 patients in 28 centers in Germany and Poland were randomized to study
treatments (144 per group, mean age 55.0 yrs, 14.2% male, mean disease duration 115.3 months). In the 3-month double-blind phase the mean relative reduction of morning stiff- Prednisone IR
Prednisone MR
ness duration was significantly higher under MR prednisone than under IR prednisone (decrease of 22.7% versus 0.4%; baseline to endpoint, p=0.0452, two-sided). A 10% differ- Relative Change in Morning Stiffness (%) SEM ence became apparent at week 2. Median IL-6 levels in the MR prednisone group decreased by 28.6% compared to zero % in the IR prednisone group. In the open phase, during whichall patients received MR prednisone, patients from the former IR-group showed a similar Pharmacokinetics
New Modified-Release (MR) Prednisone Tablet
reduction of morning stiffness and after 3 months the mean reduction of morning stiffness from baseline was 55.0% (96 minutes, p<0.0001) in all patients. This effect was sustained until the end of the follow-up (mean reduction 46.1%, 84 minutes, p<0.0001). Also in the former IR-group an analog reduction in IL-6 levels was seen and maintained until end of hydrophobic surface adsorbs air bubbles (1h) water is penetrating the shell, rupture starts (2h) CONCLUSIONS The new MR prednisone significantly reduces morning stiffness and levels
of IL-6, more than the IR prednisone and hence brings added value to the already well
known therapeutic effects of prednisone. The bedtime administration is convenient for thepatient. The achieved treatment effects were sustained over the entire 12 months treatment prednisone mean plasma concentrations (ng/ml) period. The new MR prednisone was well tolerated. core is being released and dissolved (5h)

Source: http://www.trunoc.de/downloads/Nitec-Reduced%20Morning%20Stiffness.pdf