New Data Presented at ACR Meeting Demonstrates Colcrys (Colchicine, USP) Significantly Reduces Pain of Acute Gout Flare Within 24 Hours With Side Effects Comparable to Placebo
Studies Confirm Clinical Benefit, Reveal New Information on Safety and Pharmacokinetics of Colcrys
PHILADELPHIA, Oct. 19 /PRNewswire/ -- URL Pharma, Inc., today
announced data from a pivotal Phase III study demonstrating that
Colcrys(TM) (colchicine, USP), a low-dose colchicine, reduced the
pain of gout flares within a 24-hour period as effectively as
high-dose colchicine with a side effect profile statistically
indistinguishable from placebo. These data and two other Colcrys
studies were presented this week at the 2009 American College of
Rheumatology (ACR) Annual Scientific Meeting in Philadelphia.
"These studies confirm that Colcrys offers patients effective
relief of gout flares with significantly reduced side effects and a
greater margin of safety," said Robert A. Terkeltaub, M.D., Section
Chief, Rheumatology-Allergy, VA Medical Center San Diego, and
Professor of Medicine and Rheumatology Training Program Director,
University of California San Diego. "The data provide critical
guidance for physicians on the optimal use of colchicine, and
signal a positive change in how we manage acute gout flares." Dr.
Terkeltaub was the primary investigator for the AGREE (Acute Gout
Flare Receiving Colchicine Evaluation) study presented at the 2008
ACR Annual Meeting.
Colcrys(TM) is approved for the prophylaxis and treatment of
gout flares. It is the first and only single-agent colchicine
treatment to receive FDA approval. Colcrys provides a formulation
with the same efficacy of high dose colchicine while avoiding most
of the toxicity of the unapproved products currently on the
"These clinical studies with colchicine - the first of their
kind ever conducted - have resulted in significant benefit and
value to patients living with gout," said Richard H. Roberts, M.D.,
Ph.D., President, Chief Executive Officer and Chairman of URL
Pharma. "The data presented today reaffirm the role of colchicine
as a cornerstone therapy in the treatment of gout, provide valuable
information on how to dose colchicine while reducing side effects,
and highlight potential and previously unknown drug-drug
interactions, giving physicians the information they need to
prescribe colchicine with greater confidence."
This Phase III, randomized, double-blind, placebo-controlled,
parallel group study represents a secondary analysis of the
previously presented AGREE trial data. A total of 184 patients
having a clinical diagnosis of gout according to ACR guidelines
received either study drug or placebo. Fifty-two patients received
high-dose colchicine (1.2 mg, then 0.6 mg hourly x 6 hours = 4.8 mg
total); 74 received Colcrys (1.2 mg, then 0.6 mg in 1 hour = 1.8 mg
total, followed by 5 placebo doses hourly); and 58 were assigned to
placebo (2 capsules, then 1 capsule hourly x 6 hours).
The study's primary endpoint was a 50 percent reduction in joint
pain at 24 hours post first dose. Researchers also compared pain
improvement scores at 24 and 32 hours after the first dose.
Patients recorded pain intensity (as measured by a 0-10 point
Likert pain scale) and adverse events over 72 hours.
In this analysis, 43.2 percent of patients experienced a 2 point
or greater reduction in pain on the Likert scale 24 hours after
taking Colcrys compared with 17.2 percent in the placebo group (p =
0.0015). The therapeutic effect was sustained at 32 hours
post-Colcrys dosing, with 45.9 percent of Colcrys patients
experiencing a 2 point or greater reduction in pain versus 17.2
percent in the placebo group (p = 0.0005). While the Colcrys and
high-dose colchicine groups experienced similar pain relief at 24
and 32 hours, the safety profile of Colcrys was significantly
improved over high-dose colchicine. The rate of adverse events seen
in the Colcrys-treated patients was comparable to placebo.
Additional Colcrys Studies
Two additional studies provide new data on the concomitant
dosing of colchicine with the calcium channel blocker verapamil and
additional evidence of the safety of Colcrys(TM) dosing in the
treatment of gout flares.
Verapamil Drug Interaction Study
Researchers presented a Phase I study assessing the effect of
verapamil on the pharmacokinetics of single-dose colchicine, the
first time this commonly-prescribed hypertension medication has
been evaluated for interactions with colchicine. Hypertension is
one of many co-morbid conditions often experienced by gout
patients, so an understanding of interactions with drugs often used
in conjunction with colchicine is of critical importance to
This open-label, 2-period, drug-drug interaction (DDI) study
examined 24 fasting subjects, who received a single 0.6-mg oral
dose of colchicine on Day 1. Blood samples were drawn at various
times for pharmacokinetic (PK) analysis on Days 2-5. After a 10-day
washout period, subjects received 240 mg verapamil once daily for
five days. On day 19, a second colchicine dose (0.6 mg) was given.
Blood samples were drawn for PK analysis on Days 20-23.
The study demonstrated that verapamil increases colchicine
concentrations in the blood by 30 percent. The researchers
concluded that, for the treatment of acute gout flare, the standard
dose of colchicine should be reduced from 3 to 2 tablets for
patients on verapamil or diltiazem. Colchicine dosing should be
reduced by 50 percent when administered chronically and
concomitantly with verapamil or diltiazem (another calcium channel
blocker previously studied by URL Pharma for drug-drug
Pharmacokinetic dosing of colchicine
Investigators presented a Phase I study of 75 healthy volunteers
evaluating the pharmacokinetics of Colcrys as single dose, low-dose
and high-dose regimens. Plasma samples were collected following
single-dose (0.6mg, both after food and while fasting), low dose
(1.2 mg + 0.6 mg after 1 hour) and high-dose (1.2 mg + 0.6 mg x6)
Colcrys regimens. Adverse events were assessed and cardiac safety
was measured by ECG.
Results showed that high-dose and low-dose regimens of Colcrys
had similar steady-state plasma concentrations and blood levels.
However, the high-dose regimen showed a two-fold greater total
exposure when compared with the low-dose regimen. The analysis
suggested that peak colchicine blood levels of about 6 ng/mL are
adequate for pain reduction in the first 24 hours after a gout
The investigators concluded that additional exposure from
high-dose colchicine may only increase unwanted side effects, and
recommended low-dose Colcrys (1.2 mg + 0.6 mg after 1 hr) for early
acute gout flare treatment. The most common adverse events in this
study were headache, diarrhea, dizziness, nausea, stomach pain, and
vomiting. All were mild-to-moderate and did not result in
About Gout and Painful Gout Flares
Gout is a painful form of arthritis that affects an estimated 3
to 5 million Americans, most commonly adult men. It occurs when
excess uric acid in the body is deposited as needle-like crystals,
or tophi, in the joints or soft tissues, which cause inflammatory
arthritis and can lead to gout flares typically lasting three to 10
Gout flares are characterized by intermittent swelling, redness,
heat, joint stiffness and pain, which are often excruciating and
can be debilitating enough to significantly interfere with work,
social activities and daily living. For many people, gout initially
affects the joint of the big toe, though it can also affect other
joint areas such as the ankles, heels, knees, wrists, fingers and
Important Safety Information
COLCRYS (colchicine, USP) tablets are indicated for the
prophylaxis and treatment of acute gout flares in adults.
COLCRYS is contraindicated in patients with renal or hepatic
impairment who are concurrently prescribed P-gp inhibitors or
strong inhibitors of CYP3A4 as life-threatening or fatal toxicity
has been reported. The most common adverse events in clinical
trials for the prophylaxis and treatment of gout were diarrhea and
pharyngolaryngeal pain. Rarely, myelosuppression, thrombocytopenia,
and leukopenia have been reported in patients taking colchicine.
Rhabdomyolysis has been occasionally observed, especially when
colchicine is prescribed in combination with other drugs known to
cause this effect. Monitoring is recommended for patients with a
history of blood dyscrasias or rhabdomyolysis.
You are encouraged to report negative side effects of
prescription drugs to the FDA. Visit www.fda.gov/medwatch or call
You may also report negative side effects to the manufacturer of
COLCRYS by calling 1.888.351.3786. Please see www.colcrys.com for
full Prescribing Information.
About URL Pharma
URL Pharma, Inc., headquartered in Philadelphia, PA, is a
leading specialty pharmaceutical company with fully integrated
technology development, product development, manufacturing, and
commercialization capabilities. After a long history of generic
pharmaceutical research, development, and manufacturing, the
Company has successfully transitioned to a profitable,
technology-driven, specialty pharmaceutical business. The Company
seeks to develop and commercialize scientifically and medically
innovative products that address unmet medical needs for
improvements in safety and efficacy. The Company's profits are
derived predominantly from its exclusive products and technologies.
For additional information about the company, please visit
www.urlpharma.com. For further information, please call
215-697-1900 or firstname.lastname@example.org.
Source: URL Pharma, Inc.
CONTACT: Matthew J. Scampoli, +1-646-284-7324,
Web Site: http://www.urlpharma.com/
Posted: October 2009