supplied by the sponsor were performed using t-tests (cf: Stanton A. Glantz, Primer of Biostatistics, 1992, p. 81).  No corrections were performed for multiple comparisons testing.  The only statistically significant differences between drug groups and placebo groups at baseline were: the mean 28-item HAMD score was 1.6 points greater in the 400 mg/d group than in the placebo group (p<0.05); the mean item #1 of the HAMD score was 0.2 points lower in the 200 mg/d group than in the placebo group (p<0.005); the mean CGIS score was 0.2 points higher in the 300 mg/d and 400 mg/d groups than in the placebo group (p<0.02, p<0.05, respectively).  These differences appear to have little clinical significance.

 

7.2.2.3.4             Dosing Information

 

The sponsor calculated mean daily dosages of medication intake as of the eighth day of the study (by which time patients have been titrated up to the full dosage level) through day of discontinuation.  The mean daily dose of bupropion sustained-release ingested by the 100 mg/d group was 95 mg.  The mean daily dose of bupropion sustained-release ingested by the 200 mg/d was 191 mg.  The mean daily dose of bupropion sustained-release ingested by the 300 mg/d group was 283 mg.  The mean daily dose of bupropion sustained-release ingested by the 400 mg/d group was 375 mg.

 

7.2.2.3.5             Concomitant Medications

 

Concomitant medication was administered to 87% of 100 mg/d patients, 83% of 200 mg/d patients, 86% of 300 mg/d patients, 82% of 400 mg/d patients, and 86% of placebo patients.  The most commonly administered medications were non-narcotic analgesics, miscellaneous cold preparations or antihistamines, female hormones or birth control pills, antibiotic or antiviral agents, and vitamins or dietary supplements.

 

7.2.2.3.6             Efficacy Results

 

As noted previously, the sponsor focused on the following as key efficacy variables: the 17-item HAMD, the 28-item HAMD, item #1 of the HAMD, the CGI-S, and the CGI-I.  Appendix 7.2.2.3 presents the data for these key efficacy variables with both the observed case (OC) and the last observation carried forward (LOCF) analyses.  Two-tailed t-tests were used to compare changes in each of these variables in the drug- vs. placebo-treated groups at each week of the study.  In addition, chi square “responder analyses” were conducted to test for differences in the proportions of responders in the treatment groups.  For the HAMD analyses, a patient whose total score was reduced by  50 per cent or more between baseline and discontinuation was considered a responder.  For the CGI-I analysis, a patient who was rated as “very much improved” or “much improved” at discontinuation was considered a responder.  The following is a brief summary of the findings.

 

Table 7.2.2.3.6 displays a summary of the statistical comparisons between placebo and both drug treatment groups for the outcome variables.  The reader should note that these are not independent scales.

 

 

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