Min J-H, et al. • Oral Ursodeoxycholic Acid Therapy in Amyotrophic Lateral Sclerosis with oral solubilized UDCA to those whilst on placebo. It was calculated that 48 patients, i.e., 24 patients in each treatment group, would have to be included in order to detect a difference of 10% in the mean slope of AALSRS between the two treatments with a power of 80% and an alpha risk of 5%. The sample size calculation was based on data from a previous study using the AALSRS to measure the functional deterioration in patients with ALS (26). Efficacy was analyzed using the data from the patients who completed the study without any protocol violation. No impu- tation process was performed for missing data. Data for efficacy analysis were divided into two sets of per-protocol (PP). The first PP (PP) dataset were defined as the data from the patients who completed either the first or second period of study, while the second PP (PP’) dataset consisted of the data only from the pa- tients who completed both the first and second periods of study. Data of the patients whose slopes of AALSRS were steep (defined as greater than 24 points during a 3-month period) were excluded from efficacy analysis because inclusion of those atypical pa- tients who progressed very rapidly could seriously distort the result (26). Using the SAS General linear model (GLM), analysis of covariance (ANCOVA) was performed with the slope as the dependent variable, treatment as factor, and the period and se- quence as covariates. Safety analysis was performed in all ran- domized patients who had taken at least one study drug or pla- cebo. Baseline characteristics of patients including demographic and clinical variables were compared between patients treated with oral solubilized UDCA and those with placebo. Incidence of adverse events was compared between the two treatments using the chi-square. Statistical significance was set at P < 0.05, and the results are reported with two-sided P values. Ethics statement The study was conducted according to the Declaration of Hel- sinki, and Korean Good Clinical Practice (KGCP) guidelines. The study protocol was submitted to and approved by the Korean Food and Drug Administration (KFDA) (16409), and the Insti- tutional Review Board (IRB) of Seoul National University Hos- pital (H-0301-099-007). All patients gave written informed con- sent before trial entry. Overall trial-related activities and docu- ments were overseen by an Independent Auditory Board (C&R Research, Seoul, Korea). RESULTS The trial profile is illustrated in Fig. 1. A total of 80 patients were assessed for eligibility, and 64 patients were enrolled in this study (one in error). Reasons for exclusion were the AALSRS total score greater than 120 or disease duration longer than 60 months (n = 10), severe depression (n = 3), and clinically possible ALS (n = 2) and cognitive impairment (n = 1). Forty of 63 patients were as- signed to receive oral solubilized UDCA in the first period of study, and the other 23 patients to receive placebo. During the first period, 19 of 40 (47.5%) patients treated with oral solubilized 80 patients assessed for eligibility 64 Randomized† 16 excluded* 40 received Oral UDCA 23 received placebo 19 analyzed 19 received Oral UDCA 202 http://jkms.org 4 lost to follow-up 4 discontinued d/t adverse events 9 missed visits 4 progressed rapidly‡ 3 lost to follow-up 1 discontinued d/t adverse events 8 missed visits 1 progressed rapidly‡ 6 analyzed 13 analyzed 15 analyzed 31 received placebo 2 lost to follow-up 1 discontinued d/t adverse events 5 missed visits 2 lost to follow-up 1 discontinued d/t adverse events 15 missed visits Fig. 1. Trial profile. *all not meeting inclu- sion criteria; †one ineligible patient was randomized in error; ‡excluded from anal- ysis due to a rapid rate of progression, i.e., the Appel ALS total score change > 8 points/month. http://dx.doi.org/10.3346/jkms.2012.27.2.200