Vernakalant (oral)
Cardiome is also investigating vernakalant in oral form for the chronic treatment of atrial fibrillation relapse. Vernakalant (oral) is expected to prevent or slow the recurrence of AF, and is designed to be used as a follow-on therapy to vernakalant (iv).
Phase 2a Trial
In Q3-2006, Cardiome announced top-line results from both the 300mg and 600mg dosing groups for a Phase 2a pilot study of vernakalant (oral). The study was initiated in Q4-2005.
For the 300mg dosing group, 61% (33 of 54) of patients receiving vernakalant (oral) completed the study in normal heart rhythm, as compared to 43% (24 of 56) of all patients receiving placebo. For the 600mg dosing group, 61% (30 of 49) of patients receiving vernakalant (oral) completed the study in normal heart rhythm, as compared to 43% of all patients receiving placebo.
A Kaplan-Meier analysis of the results demonstrated a statistically significant efficacy difference between the 300mg dosing group and the placebo group (p=0.048). The difference between the 600mg dosing group and the placebo group trended toward but did not reach statistical significance (p=0.060). A combined analysis of all drug group patients relative to the placebo group also demonstrated a statistically significant difference (p=0.028).
For the entire study, a total of 171 patients were successfully cardioverted after the initial 3 days of dosing and continued in the study, of which 159 reached an endpoint of the study (completion of dosing or relapse to atrial fibrillation). The remainder of the patients were discontinued from the study for reasons unrelated to atrial fibrillation.
The safety data for both dosing groups suggests that vernakalant (oral) appears well-tolerated within the target population. During the 28 days of oral dosing, serious adverse events occurred in 8% of all placebo patients, 10% of patients in the 300mg dosing group, and 11% of patients in the 600mg dosing group. Potentially drug-related serious adverse events occurred in 1% of all placebo patients, 4% of patients in the 300mg dosing group and 5% of patients in the 600mg dosing group. There were no cases of drug-related “Torsades de Pointes”, a well-characterized arrhythmia which is an occasional side effect of some current anti-arrhythmic drugs.
The double-blind, placebo-controlled, randomized, dose-ranging study was designed to explore safety and tolerability, pharmacokinetics and preliminary efficacy of vernakalant (oral) over 28 days of dosing in patients at risk of recurrent atrial fibrillation. The majority of patients enrolled had experienced atrial fibrillation for greater than 30 days and less than 180 days in duration. Patients received a 300mg dose of vernakalant (oral), a 600mg dose of Vernakalant (oral) or placebo twice per day. After the first 3 days, patients still in atrial fibrillation were electrically cardioverted. Successfully cardioverted patients continued to receive vernakalant (oral) or placebo for the remaining 25 days and were monitored throughout the dosing period. Cardiome initiated the Phase 2a pilot study of vernakalant (oral) in December 2005. The study was conducted across 72 centres in Canada, U.S. and Europe.
Phase 2b Trial
In Q1-2007, Cardiome initiated a Phase 2b clinical trial of vernakalant (oral) for the prevention of recurrence of atrial fibrillation.
The double-blind, placebo-controlled, randomized, dose-ranging study was designed to explore safety and tolerability, pharmacokinetics and efficacy of vernakalant (oral) over 90 days of dosing in patients at risk of recurrent atrial fibrillation. Patients received a 150mg, 300mg or 500mg dose of vernakalant (oral) or placebo twice per day. After the first 3 days, patients still in atrial fibrillation were electrically cardioverted. Successfully cardioverted patients continued to receive vernakalant (oral) or placebo for the remainder of the 90-day trial and were monitored throughout the dosing period.
Enrollment for this study has completed, with a total of 735 patients randomized of which approximately 590 patients are expected to enter the maintenance phase and be measured for efficacy. Final results from the study are expected in the third quarter of 2008.
In March 2008, Cardiome announced positive interim results from this study. (link)