DEERFIELD, IL, and VANCOUVER, March 25 /PRNewswire-FirstCall/ - AstellasPharma US, Inc. and its co-development partner Cardiome Pharma Corp. announcedthe first pivotal Phase III study evaluating the investigational agentKYNAPID(TM) (vernakalant hydrochloride) Injection was published today inCirculation, the official journal of the American Heart Association.
In the study, known as the Atrial arrhythmia Conversion Trial (ACT I), theprimary efficacy analysis showed that 75 of the 145 (51.7%) KYNAPID patientsin the short-duration atrial fibrillation (AF) group (3 hours to 7 days)converted to sinus rhythm within 90 minutes compared with 3 of the 75(4.0%)placebo patients. Patients with AF lasting 3 to 48 hours who received KYNAPIDdemonstrated the highest conversion rate (62.1%) compared with 4.9% withplacebo. The median time to conversion to sinus rhythm for the 75 patientsreceiving KYNAPID who converted was 11 minutes. Only 1 of the 75KYNAPID-treated patients who converted to sinus rhythm relapsed to AF at 24hours.
"Due to the importance of treating AF quickly, we're pleased that KYNAPIDdisplayed such a rapid conversion of AF to sinus rhythm," said EdwardPritchett, MD, Consulting Professor of Medicine, Divisions of Cardiology andClinical Pharmacology, Duke University Medical Center and consultant forAstellas Pharma US.
About ACT I
The Phase III study, referred to as ACT I, was a prospective, randomized,double-blind, placebo-controlled trial of hemodynamically stable patients withsymptomatic AF or nontypical atrial flutter, conducted at 44 sites in Canada,the United States and Scandinavia. The study assessed the safety and efficacyof KYNAPID for the conversion of AF. Results of the study showed KYNAPIDdemonstrated rapid conversion of short-duration AF and was well tolerated.
The efficacy and safety evaluable populations included 220 patients in theshort-duration AF group and 116 patients in the long-duration AF group.Patients with AF were randomly assigned in a 2:1 ratio to KYNAPID 3 mg/kg orplacebo infused over 10 minutes. After 15 minutes, a second 10 minute infusionof KYNAPID 2 mg/kg or placebo was given if AF persisted or atrial flutter waspresent. The primary efficacy measure was the percentage of patientsdemonstrating conversion to SR for at least one minute within 90 minutes ofdosing in the short-duration AF group.
The most common adverse events (AEs) reported within the first 24 hours inpatients given KYNAPID were taste disturbance (29.9%), sneezing (16.3%), skinsensation (10.9%), nausea (9%), and hypotension (6.3%). These events weregenerally transient. Four serious AEs possibly or probably related to KYNAPIDoccurred in three patients and included hypotension (2 events), completeatrioventricular block and cardiogenic shock.
About Atrial Fibrillation
AF is an interruption of the normal sinus rhythm (arrhythmia) of the heartin which the atria, the two uppermost chambers of the heart, beat irregularlyand at an extremely rapid rate. During AF, rapid and uncoordinated electricaldischarges are generated by the heart's natural pacemaker (sinoatrial node)and other parts of the atria. This causes ineffective contractions of theatria and reduces the ability of the heart to pump blood through the body.Symptoms include dizziness, heart palpitations, weakness, shortness of breathand angina (chest pain). AF is the most common cardiac arrhythmia. AF patientsare three to five times more likely to develop stroke, and 15% of stroke casesare attributed to AF. The number of AF patients is expected to triple over thenext 50 years due to the increased prevalence of risk factors includinghypertension, obesity, diastolic dysfunction, inflammation, diabetes and sleepapnea.
Astellas Pharma US, Inc., located in Deerfield, Illinois, is a U.S.affiliate of Tokyo-based Astellas Pharma Inc. Aste