Trial Outcomes & Findings for Effect of Donepezil on Smoking (NCT NCT01250977)

Thirty subjects were consented and screened for eligibility at an Intake Visit at the Center for Interdisciplinary Research on Nicotine Addiction (Philadelphia, PA).

Twenty subjects ultimately completed a Baseline Visit and were randomized to receive Donepezil or Placebo.

Effect of Donepezil on Smoking

Neurocognitive task performance was assessed during baseline and each testing day (Day 7, 14, 21, and 28) using computerized tasks. Working memory was assessed with the Letter-N-back task.

Sustained attention was assessed with the Penn Continuous Performance Task (P-CPT). The primary outcome measure was the change from Baseline in discriminability (score) on the P-CPT at Day 28. The discriminability score is the mathematical difference between the total correct (i.e., true positives and correct non-responses) and incorrect (i.e., errors of commission and omission) responses to a series of stimuli presented during the P-CPT. The unit of measure is number of correct responses less the number of incorrect responses. A higher discriminability score at a single time point indicates a better performance on the P-CPT. A positive change in discriminability score between Baseline and Day 28 indicates improved performance over time. In its purest mathematical sense, the discriminability measure is a difference of difference scores and therefore is without scale limits, that is, there are no minimum or maximum values one could theoretically obtain.

At each visit, smoking rate (i.e., cigarettes per day) was assessed using standard Timeline Followback methods. Weekly averages were computed to assess group differences in changes in smoking behavior from Baseline to Day 28.

A 38-item self-report measure of the side effects associated with Donepezil (e.g., nausea) was administered to all participants at observation and testing days through Day 28. For each item, side effect severity was rated on a 4-point scale (0 = not present, 1 = mild, 2 = moderate, 3 = severe). The side effect summary score from the measure collected at Day 28 was considered the dependent measure because Day 28 is when the medication reached steady state. The side effect summary score was calculated by taking the mean score (i.e., sum of all 38 items \[each item rated on a scale 0-3\] divided by 38) of the measure from each participant at Day 28, adding the means, and then dividing the sum of the means by the number of participants within each group. A higher summary score indicates a higher general incidence rate and severity of side effects.