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All AEs were mild or moderate and none were serious or led to subject discontinuation.
There were no adverse events that resulted in subject discontinuation from the study.
Including the replacement subjects, a total of 26 subjects were enrolled in arm A and 30 subjects in arm B. Overall, 12 of the 56 subjects were enrolled into the study as replacements, with 4 such subjects randomized into arm A and 8 into arm B. The timing and reasons for subject discontinuation from the study are summarized in Table 1.
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No subjects were withdrawn due to changes in ECG or QT interval, resulting in minimal bias from subject discontinuations.
Canagliflozin was associated with higher rates of genital mycotic infections in females (e.g., vulvovaginitis) and males (e.g., balanitis) compared with sitagliptin, which led to one study discontinuation (male subject) and no serious AEs, and responded to usual treatment with antifungal agents.
Because the real reason for study discontinuation in these subjects is not known, this could result in an underestimation of important reasons for patients dropping out, including AEs or lack of efficacy.
Sixty subjects (15.3%) experienced at least one treatment-related adverse event; such events led to study discontinuation for 20 (5.1%) subjects.
The most common reasons for early study discontinuation were adverse events and subject decision (Fig. 1 B ).
However, as two of the patients had met their individual FEV1 discontinuation criterion, the study discontinuation criterion "Two or more subjects, who receive AZD9164, have other clinically significant changes in laboratory values or other safety parameters" was also met.
The related overall study discontinuation criterion was 'Two or more subjects, who receive AZD9164, have other clinically significant changes in laboratory values or other safety parameters'.
Treatment-emergent AE resulted in study discontinuation in 14.9% of SXB 4.5 g/night subjects and 20.6% of SXB 6 g/night subjects versus 5.3% for placebo.
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