Cardiome completes trial for anti-arrhythmic drug
controlled release oral formulation of RSD1235, an anti-arrhythmic
drug candidate that could well provide an effective drug therapy
for its 7 million sufferers worldwide.
RSD1235 is designed to be an acute-use, intravenous (IV) administration treatment for termination of atrial fibrillation (AF) and a chronic-use oral drug for the maintenance of normal heart rhythm following termination of AF. RSD1235 selectively blocks ion channels in the heart that are known to be active during episodes of AF.
Cardiome reported Phase 3 results for IV RSD1235 in December 2004. Of the 237 patients with recent-onset atrial fibrillation (AF), 52 per cent of those receiving an IV dose of RSD1235 converted to normal heart rhythm, as compared to 4 per cent of placebo patients.
The completed phase 1b study evaluated the safety and efficacy of oral RSD1235 as a function of fed and fasted states in normal and poor metabolisers. The study confirmed that RSD1235 was well absorbed and tolerated in all subjects. Absorption was not influenced by a fed or fasted state.
On the basis of these results, Cardiome has now begun enrolling patients into a Phase 1c study evaluating safety and tolerability after multi-day dosing.
The Phase 1b study examined the effect of food and fasting on the absorption of RSD1235. Patients took a single controlled release tablet either immediately following a meal or without eating. A multi-day dosing study was then initiated to assess the pharmacokinetics and safety of repeated daily doses of controlled release RSD1235 tablets.
Oral RSD1235 will be studied in patients to confirm the ability of the novel agent to prevent or delay the reoccurrence of AF. Oral RSD1235 is designed to be used as a follow-on therapy to intravenous RSD1235, currently in its second and third Phase 3 trials for the conversion of AF.
In September 2004, Cardiome initiated patient dosing in its first phase I study of a controlled release formulation of oral RSD1235. The study was an open label, cross over evaluation of two controlled release formulations of RSD1235 in comparison to an immediate release formulation. In November 2004, Cardiome completed this Phase I study and announced the selection of this oral formulation to take forward for further clinical development.
Atrial fibrillation is a debilitating disease that affects approximately 7 million people worldwide. Arrhythmia is often associated with other forms of heart disease and is a leading contributor to stroke, congestive heart failure and sudden cardiac arrest.
Atrial fibrillation (AF) refers to fibrillation of the upper chambers of the heart (atria) that normally pump blood to the ventricles. Instead of beating in a coordinated manner at a usual rate of 60-80 beats per minute, the atria "fibrillate" or quiver at an irregular rate of 600-1000 contractions per minute. When fibrillation occurs it is serious and rapidly fatal.
Prevention and treatment of chronic AF can also consist of drug therapy. Current drugs available offer a much slower onset of action as well as the possibility of inducing further arrhythmia reducing blood pressure or heart rate, and toxicity in other organs.
Alternatives include focal ablation, which is expensive, complicated, and requires a permanent pacemaker, or surgery, which may result in permanent heart damage.
