0 ± 9.4 73.86 ± 10.38 25.50 ± 2.37 Range 18–73 146.0–195.0 49.00–106.10 19.55–29.70 Median

48 170.0 75.00 25.63 BMI body mass index, SD standard deviation A total of 153 healthy subjects were randomly assigned to a treatment in accordance with the computer-generated blocks randomization scheme (block size 6, randomly variable). The randomization scheme was generated using Statistical Analysis System® (SAS®) program version 9.2 (SAS Institute Inc., Cary, NC, USA). This program used the randomized block design to ensure an equal distribution of sequences at multiples of 6 in the list of subject assignment. R428 clinical trial Based on results of a previous pilot study, the within-subject coefficients of variance (CVs) should be approximately 39 and 48 % for AUC and C max, respectively. Thus, with these expected CVs and an expected ratio of AUC and C max within 0.90 and 1.11, the study should have a power of at least 90 % to show bioequivalence with 138 subjects. In order to account for possible dropouts, 153 subjects were included in the study. 2.3 Study Design This study was a single-centre, randomized, single-dose, open-label, three-way, three-sequence,

reference formulation-replicated, crossover bioequivalence study to compare the rate and extent of absorption of Tecnimede’s test formulation of ibandronic acid (batch number 15044; expiration date: 04-2013; manufactured by West Pharma, SA, Portugal) with the reference formulation (batch number B1176B01; Selleck Adriamycin expiration date: 11-2015; manufactured by Roche Pharma AG, Germany), acquired in the Polish market, under fasting conditions, in healthy volunteers. After an overnight fast of at least 10 hours, subjects were dosed in the mornings. Subjects were administered the test or the reference formulation, as per the randomization scheme, as a single oral dose of one film-coated tablet containing 150 mg of study medication, with 240 mL of water. Subjects were dosed as specified in the protocol, and subsequently fasted for

a period of at least 4 hours. Subjects were served Glycogen branching enzyme a controlled meal not less than 4 hours post-dose, and at appropriate times thereafter, in each period. Subjects were served standardized post-dose meals similar in composition in each period. With the exception of the volume administered at the time of dosing, fluids were not permitted from 1 hour before dosing to 1 hour after dosing, but, after that period, plain water was permitted ad libitum. According with a reference formulation-replicated design, the study had three periods (period 1, period 2 and period 3) and the subjects were randomized to three sequences (test-reference-reference [TRR]; reference-reference-test [RRT] and reference-test-reference [RTR]). In each study period, subjects were administered the test formulation (Treatment A) or the reference formulation (Treatment B) as per the randomization scheme.