Joint Pain Forum – News you can use!
CombinatoRx,
Incorporated (CRXX) Says Arthritis Drug Misses Primary Endpoint; Stock
Falls
26
Mar 2007
CombinatoRx,
Incorporated (NASDAQ: CRXX) today announced preliminary
results of a phase 2 clinical trial studying CRx-139 (a synergistic
combination of 3mg prednisolone and the antidepressant paroxetine) and
3mg prednisolone alone, in patients with rheumatoid arthritis (RA).
CAMBRIDGE,
MA, USA | Mar 26, 2007 | CombinatoRx,
Incorporated (NASDAQ: CRXX) today announced preliminary results of a
phase 2 clinical trial studying CRx-139 (a synergistic combination of
3mg prednisolone and the antidepressant paroxetine) and 3mg
prednisolone alone, in patients with rheumatoid arthritis (RA). This
trial served two important purposes. One purpose was to determine the
effect of 3mg of prednisolone alone (a very low dose) in RA and to
contrast this effect with the activity previously reported with
CRx-102, a synergistic combination of very low dose prednisolone and
dipyridamole. The results with 3mg prednisolone confirm that the
anti-inflammatory benefits previously observed in three phase 2a
clinical trials with CRx-102 are due to the synergistic activity of
CRx-102’s components, as opposed to an effect derived from the
prednisolone component alone. Another purpose of the trial was to
evaluate the activity of CRx-139 vs. prednisolone alone. CRx-139 did
not show statistical significance on the primary endpoint of the trial.
CRx-139 did show statistical significance on multiple other endpoints,
requiring further analysis.
CRx-102
Confirmed as Superior to Prednisolone Alone and Advances on Plan in RA
and OA
Comparison
of treatment outcomes for CRx-102 (from previously reported results in
RA) versus very low dose prednisolone alone (from the study reported
here) shows that CRx-102 is superior to the 3mg of prednisolone alone.
Importantly, subjects in the two studies had the same demographics and
similar baseline disease status, allowing for comparison of study
results. The following table summarizes the ACR 20 scores for CRx-102
and low dose prednisolone, respectively, at 6 weeks, the duration of
the CRx-102 RA study.
Trial
Regimen Patients Achieving ACR 20 (Per Protocol) Patients Achieving ACR
20 (Intent To Treat)
CRx-102-002
CRx-102 63% 54% CRx-139-002 3mg prednisolone 36% 37%
“This
trial confirms that the strong clinical activity previously reported
with CRx-102 should not be attributed to the effect of its low dose
prednisolone component alone,” said Alexis Borisy, President and CEO of
CombinatoRx. ”We are pleased to have this additional validation of our
combination sciences approach to selective steroid amplification, and
we look forward to rapidly advancing CRx-102 as our lead dissociated
steroid combination for the treatment of RA and OA.”
CRx-139
Misses
Primary Endpoint, Shows Significance on Multiple Other Endpoints,
Requires Further Analysis
While CRx-139 was not
statistically significant vs. 3mg prednisolone as measured by ACR 20 at
day 70, CRx-139 did achieve statistical significance vs. 3mg
prednisolone alone as measured by ACR 20 and ACR 50 at earlier time
points. Full analysis of the CRx-139 data is ongoing.
In
this trial, CRx-139 was generally well tolerated and there were no
drug-related serious adverse events reported for subjects treated with
CRx-139. The most common adverse events observed with CRx-139 that
occurred with a frequency of greater than 5% (9% or less) were headache
and nausea, known side effects of paroxetine, one of the two components
of CRx-139.
About
the Trial Design
This
trial was a multi-center, blinded, randomized study evaluating the
effectiveness of two doses of CRx-139 (containing 10 or 20mg paroxetine
with prednisolone) and 3mg of prednisolone in a 1:1:1 ratio in subjects
with active RA who were on stable disease modifying anti-rheumatic drug
(DMARD) therapies. The primary endpoint was ACR 20 response at day 70.
Other endpoints of the trial included ACR 50 and ACR 70 responses and
DAS28 scores. Additional endpoints are being analyzed and will be
presented at appropriate scientific venues.
209
patients with established RA and moderate to severe disease activity
with >6 tender and >4 swollen joints were enrolled in
this study. Patients had to be on a DMARD therapy (such as methotrexate
or sulfasalazine) for at least 3 months and be on a stable dose of
DMARD therapy for a minimum of 1 month (2 months for methotrexate)
prior to enrollment. CRx-139 was dosed in this trial using 3mg of
prednisolone and two different doses of paroxetine. All patients
received 3mg of prednisolone alone during the first 2 weeks (baseline)
and then were randomized to also receive either 10mg or 20mg of
paroxetine or placebo for the following 8 weeks (combination treatment
period). Each arm was then deconvoluted into the individual components
(3mg of prednisolone and 10 or 20mg of paroxetine or 3mg prednisolone
and placebo alone) for the remaining 4 weeks (withdrawal period).
The
ACR 20 score is a standard measure developed by the American College of
Rheumatology to rate RA disease improvement. Patients are classified as
ACR 20 responders if they demonstrate a 20% improvement from baseline
in tender and swollen joint count and at least 3 of 5 other symptom
related criteria. The Disease Activity Score using 28 joint counts
(DAS28) is a composite score used to monitor disease activity in RA
patients.
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