Cardiome Pharma Corp has commenced patient dosing in its initial Phase III efficacy study of RSD1235 for the acute treatment of atrial fibrillation. The initial study, called ACT 1 (Atrial fibrillation Conversion Trial 1), will measure the safety and efficacy of RSD1235 in 420 patients. The placebo-controlled study is being carried out in 45 centers in the US, Canada, and Scandinavia. ACT 1 is the first of an expected three Phase III studies required for FDA approval of RSD1235.
Atrial fibrillation is an abnormal heart rhythm that affects the atria of the heart, lowering the heart's pumping capacity and increasing the risk of stroke. Immediate symptoms are breathlessness and fatigue. Long-term effects include increased risk of both stroke and congestive heart failure. More than 6 million patients in North America, Europe and Japan suffer from atrial fibrillation.
"We are happy to commence this study on our planned schedule," said Dr. Alan Moore, Executive Vice-President of Clinical and Regulatory affairs. "We are confident that RSD1235 is both effective and safe, and are now focused on conducting the study in the fastest time frame possible."
The ACT 1 study will be mainly focused on recent-onset atrial fibrillation patients. It will include a sub-study of 60 patients with atrial flutter, a less serious form of atrial arrhythmia. The primary efficacy endpoint will be acute conversion of atrial arrhythmia to normal heart rhythm. Safety observations focus on neurological and cardiovascular effects of the drug, with particular emphasis on lack of side-effect arrhythmias. The study is expected to take 18 to 24 months to complete.
The ACT 1 study protocol was designed with the input of leading research cardiologists, including the co-principal investigators of the trial, Dr.Craig Pratt from Baylor College of Medicine and Dr. Denis Roy from the Montreal Heart Institute. The Data Safety Monitoring Board for the study is chaired by Dr. John Camm of St George's Hospital, London, a long-time leader in antiarrhythmic drug research.
RSD1235 is currently formulated for intra-venous use as an acute treatment for recent-onset atrial fibrillation. In previous studies in these patients, RSD1235 terminated atrial fibrillation in 61% of the patients and was well tolerated with no significant drug-related adverse events observed. Subsequent studies also showed that RSD1235 is well absorbed when administered via oral dosing. The Company expects to begin work in 2003 to develop an oral version of the drug to potentially be used as a prophylactic agent to slow the return of terminated atrial fibrillation.
The medical community has identified a pressing need for safer and more effective antiarrhythmic drugs. While significant progress has been made in understanding the mechanisms of atrial arrhythmia, currently available drugs to treat the condition lack sufficient efficacy and put patients at risk for occasionally fatal side-effect arrhythmias. Because of the limitations of these existing drug treatments for atrial fibrillation, most such patients are treated with electo-shock therapy. This invasive and expensive therapy is disliked by both patients and cardiologists. The unique mechanism of action of RSD1235 suggests that the drug may be able to effectively treat atrial arrhythmia with a high margin of safety, reducing the need for such electro-shock therapy.