Of these, 34 withdrew consent, 7 were lost to follow-up, 2 reported scheduling difficulties, and 1 subject (assigned to 2,700 mg/day) discontinued because of an adverse effect (diarrhea). Dropout rates did not differ significantly by treatment group (p = .91). Of the 44 participants discontinuing during MEK162 ARRY-162 the medication phase, 6 (1, 1, and 4 receiving placebo; 1,800; and 2,700 mg/day, respectively) did not attend any study visits after starting medication. Among the remaining participants, there were 4 (2, 2, 0), 7 (4, 2, 1), 6 (2, 3, 1), 8 (2, 5, 1), 5 (1, 0, 4), 3 (1, 0, 2), 4 (2, 0, 2), and 1 (0, 1, 0) whose last attended visit was after 1, 2, 3, 4, 5, 6, 8, and 10 weeks of medication, respectively. Of those who discontinued during the medication phase, 91% (40/44) reported smoking at the last study visit they attended (15/15 vs.
12/14 vs. 13/15 for placebo; 1,800; and 2,700 mg/day, respectively; Fisher��s exact test p = .44). Adverse effects Adverse events considered possibly, probably, or definitely related to study drug did not differ significantly across groups. The specific adverse events and number of subjects reporting these events in each dose group (placebo; 1,800; and 2,700 mg/day) included dizziness (1, 4, 4), decreased concentration (0, 3, 0), edema (1, 2, 0), sleep disturbance (3, 0, 0), ataxia (0, 1, 1), dry mouth (0, 2, 0), fatigue (0, 2, 0), headache (1, 1, 0), nausea (1, 1, 0), rash (0, 1, 1), hand tremors (0, 0, 1), increased energy (0, 1, 0), and polyuria (0, 0, 1). Adequacy of blinding and perceived efficacy Of the 36 subjects who completed the medication phase, 34 completed an exit survey.
The percentage of subjects who correctly guessed their treatment assignment on this survey was similar across groups (5/11 for placebo; 6/12 for 1,800 mg/day; and 7/11 for 2,700 mg/day; p = .91). The mean perceived helpfulness of medication did not differ significantly across groups (4.3 �� 2.8 vs. 4.2 �� 3.4 vs. 2.8 �� 2.1 for placebo; 1,800; and 2,700 mg/day, respectively; p = .41). Discussion No meaningful differences in smoking abstinence outcomes between treatment groups were detected. Compared with baseline, all treatment groups significantly reduced the number of cigarettes smoked per day, but smoking reduction did not differ between treatment groups. Participant dropout rates were notably high with more than one half of subjects in each study arm discontinuing prior to the end of the medication phase.
Our ability to interpret the negative study findings is compromised by the high dropout rate. Two possible reasons for the high dropout rate are difficulty with the three Batimastat times daily dosing regimen and lack of efficacy. In support of the former hypothesis, five participants (14% of those who completed exit surveys) noted that they had difficulty adhering to the three times daily dosing regimen.