AD7.2.3.2.4          Efficacy Assessments

 

The 21-item HAMD, the Clinical Global Impression for Severity of Illness (CGI-S), the Clinical Global Impression for Improvement of Illness (CGI-I), and the Montgomery-Asberg Depression Rating Scale (MADRS) constituted the efficacy measures and were performed at each weekly visit.  A screening visit occurred at the onset of placebo washout.  A baseline (Day 0) visit occurred one week later at which time participating patients were randomly assigned to receive treatment.  The remaining visits occurred at one week intervals over the following eight weeks.

 

AD7.2.3.2.5          Safety Assessments

 

Safety assessments included assessment of vital signs at screening and baseline, and weight at screening, baseline, and discontinuation from treatment phase.  An adverse experience probe was administered at each visit by investigators.

 

AD7.2.3.2.6          Analysis/Plan

 

The sponsor designated the following a priori efficacy parameters: 21-item HAMD score, HAMD depressed mood (item #1), MADRS total score, MADRS apparent sadness and reported sadness scores (items #1 and #2, separately and combined), CGI-S rating, and CGI-I rating.  The analysis and non-parametric “responder” analysis was specified for that data.

 

AD7.2.3.3              Study Conduct/Outcome

 

AD7.2.3.3.1          Patient Disposition

 

A total of 456 patients constituted the baseline sample and the intent-to-treat sample (those patients receiving at least one dose of their assigned medication and having at least one efficacy assessment after baseline) constituted 434 patients.  The intent-to-treat sample consisted of 145 patients assigned to placebo, 145 patients assigned to 150 mg/d bupropion sustained-release and 144 patients assigned to 300 mg/d bupropion sustained-release.  Of the intent-to-treat sample, 69 per cent of placebo patients, 76 per cent of 150 mg/d drug-treated, and 70 per cent of 300 mg/d drug-treated patients completed the study.  Overall, 311 patients (71% of the intent-to-treat sample) completed the study.  Appendix AD7.2.3.3 shows the patient completion rates by week for each treatment group.

 

The highest proportion of dropouts occurred in the placebo group and the lowest in the 150 mg/d drug group.  An ill-characterized category of “consent withdrawn” was the most common cause for early termination.  Because some of the patients may have experienced adverse events before withdrawing consent to participate, the actual role of adverse experiences leading to premature study discontinuation may be larger than stated by the sponsor.  Table AD7.2.3.3.1 lists reasons for premature discontinuation by treatment group.

 

 

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