Takeshi Yamashita1, Takanori Ikeda2, Yasuhiko Akita3. 1. The Cardiovascular Institute, Tokyo, Japan. Electronic address: yamt-tky@umin.ac.jp. 2. Department of Cardiovascular Medicine, Toho University Faculty of Medicine, Tokyo, Japan. 3. Research & Development Department, TOA EIYO Ltd., Saitama, Japan.
Abstract
BACKGROUND: TY-0201 (TY) is a transdermal patch containing bisoprolol. The objectives of this study were to evaluate the noninferiority of TY to bisoprolol oral formulation (BO) in patients with persistent or permanent atrial fibrillation (AF). METHODS: In this multicenter, double-blind, comparative study, Japanese patients with persistent or permanent AF were randomized to TY 4-mg (n=55), TY 8-mg (n=55), BO 2.5-mg (n=55), or BO 5-mg (n=55) groups. All patients were administered TY 4mg or BO 2.5mg once a day for the first 2 weeks. Patients in the TY 8-mg or BO 5-mg group, in whom dose escalation was required, were administered TY 8mg or BO 5mg for a further 2 weeks, and the other patients continued to receive TY 4mg or BO 2.5mg. The primary endpoint was a change in 24-h mean heart rate (mHR) from baseline by Holter electrocardiogram, and the noninferiority of the TY 4-mg to the BO 2.5-mg groups and that of the TY 8-mg to the BO 5-mg groups were evaluated. RESULTS: Adjusted means of changes in 24-h mHR from baseline in the TY 4-mg, TY 8-mg, BO 2.5-mg, and BO 5-mg groups were -12.3, -13.8, -12.7, and -14.3bpm, respectively. Differences between values for the TY 4-mg and BO 2.5-mg groups and between values for the TY 8-mg and BO 5-mg groups were estimated to be 0.5 (95% CI: -1.9 to 2.9) and 0.5 (-1.9 to 2.9)bpm, respectively, which did not exceed the predefined noninferiority margins. The incidence of adverse events did not differ between the groups. CONCLUSIONS: In Japanese patients with persistent or permanent AF, TY 4mg and TY 8mg had heart rate-reducing effects similar to those of BO 2.5mg and BO 5mg, respectively.
RCT Entities:
BACKGROUND:TY-0201 (TY) is a transdermal patch containing bisoprolol. The objectives of this study were to evaluate the noninferiority of TY to bisoprolol oral formulation (BO) in patients with persistent or permanent atrial fibrillation (AF). METHODS: In this multicenter, double-blind, comparative study, Japanese patients with persistent or permanent AF were randomized to TY 4-mg (n=55), TY 8-mg (n=55), BO 2.5-mg (n=55), or BO 5-mg (n=55) groups. All patients were administered TY 4mg or BO 2.5mg once a day for the first 2 weeks. Patients in the TY 8-mg or BO 5-mg group, in whom dose escalation was required, were administered TY 8mg or BO 5mg for a further 2 weeks, and the other patients continued to receive TY 4mg or BO 2.5mg. The primary endpoint was a change in 24-h mean heart rate (mHR) from baseline by Holter electrocardiogram, and the noninferiority of the TY 4-mg to the BO 2.5-mg groups and that of the TY 8-mg to the BO 5-mg groups were evaluated. RESULTS: Adjusted means of changes in 24-h mHR from baseline in the TY 4-mg, TY 8-mg, BO 2.5-mg, and BO 5-mg groups were -12.3, -13.8, -12.7, and -14.3bpm, respectively. Differences between values for the TY 4-mg and BO 2.5-mg groups and between values for the TY 8-mg and BO 5-mg groups were estimated to be 0.5 (95% CI: -1.9 to 2.9) and 0.5 (-1.9 to 2.9)bpm, respectively, which did not exceed the predefined noninferiority margins. The incidence of adverse events did not differ between the groups. CONCLUSIONS: In Japanese patients with persistent or permanent AF, TY 4mg and TY 8mg had heart rate-reducing effects similar to those of BO 2.5mg and BO 5mg, respectively.