7.2.1.2.4             Efficacy Assessments

 

The 17-item HAMD, a 28-item HAMD including eight atypical vegetative symptom items and three items addressing helplessness, hopelessness, and worthlessness, the Clinical Global Impression for Severity of Illness (CGI-S), and the Clinical Global Impression for Improvement of Illness (CGI-I) 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.

 

 

7.2.1.2.5             Safety Assessments

 

Safety assessments included physical examinations, clinical laboratory tests, electrocardiograms at the discretion of the individual investigators, and an adverse experience probe by investigators.

 

7.2.1.2.6             Analysis/Plan

 

The sponsor designated the following a priori efficacy parameters: 17-item HAMD score, the 28-item HAMD, HAMD depressed mood (item #1), CGI-S rating, and CGI-I rating.  The analyses were performed using observed scores and last observation carried forward scores.  Parametric analysis and non-parametric “responder” analysis was specified for the data.

 

7.2.1.3                  Study Conduct/Outcome

 

7.2.1.3.1             Patient Disposition

 

A total of 362 patients constituted the baseline sample and the intend-to-treat sample (those patients receiving at least one dose of their assigned medication and having at least one efficacy assessment after baseline) constituted 342 patients.  The intent-to-treat sample consisted of 116 patients assigned to placebo, 113 patients assigned to 150 mg/d bupropion sustained-release and 113 patients assigned to 300 mg/d bupropion sustained-release.  Forty-eight per cent of placebo patients, 57 per cent of 150 mg/d drug-treated, and 55 per cent of 300 mg/d drug-treated patients completed the study.  Overall, 182 patients (53% of the intent-to-treat sample) completed the study.  Appendix 7.2.1.3 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 300 mg/d drug group.  An ill-characterized category of “consent withdrawn” was the most common cause for early termination among drug-treated groups, while inadequate response was the most common cause for early termination among placebo patients.  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 7.2.1.3.1 lists reasons for premature discontinuation by treatment group.

 

 

 

 

 

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