statistical significance between the 150 mg/d group and placebo and a significant difference (Yates X²=5.32, df-1, p=0.021) between the 300 mg/d group and placebo.

 

7.2.1.4                  Conclusion

 

The parametric analyses show inconsistent results across outcome measures, no clear evidence of an expected dose-response relationship, nor a consistency between LOCF and OC analyses.  Had there been statistical correction for multiple-time-point or multiple-dose testing, then the data in favor of efficacy of either dose of bupropion sustained-release would be even weaker.  Except for the CGI-I scale, the non-parametric analyses are not consistent across outcome measures, do not provide clear evidence of a dose-response relationship, and do not provide statistically significant evidence of the effect of bupropion sustained-release.  The non-parametric analysis of the CGI-I scale alone does support efficacy of 300 mg/d of bupropion sustained-release.  On balance, although no specific standard of efficacy was established in the design of this study, the data from protocol 203 fail to show convincing evidence of the efficacy of either of the two doses of bupropion sustained-release that were tested.

 

7.2.2                       Study 205

 

7.2.2.1                  Investigators and Location

 

Eleven U.S.A. sites participated in this trial.  The principal investigators were J.T. Apter at Princeton Biomedical Research, Princeton, NJ, R.J. Bielski at the Institute for the Study of Mood Disorders, Okemos, MI, J.L. Claghorn of Houston, TX, D. Dunner of Seattle, WA, J.M. Ferguson at Pharmacology Research Corporation, Murray, UT, J.W. Jefferson at Dean Foundation, Madison, WI, B.L. Kennedy at the University of Louisville, Louisville, KY, C. Merideth of San Diego, CA, R.K. Shrivastava at Eastside Comprehensive Medical Services of New York, NY, S.M. Stahl of San Diego, CA, and R. Weisler of Raleigh, NC.

 

7.2.2.2                  Study Plan

 

7.2.2.2.1             Objective/Rationale

 

The objective of this trial was to compare the safety and efficacy of four doses of bupropion sustained-release and placebo in the treatment of patients with major depression.

 

7.2.2.2.2             Population

 

·         The following summarizes inclusion criteria for the study:

·         Age greater than 17 years old

·         Good physical health

·         Meeting DSM-III-R criteria for Major Depressive Disorder, with a current Major Depressive Episode of between four weeks and two years duration

·         Scores of at least 20 on the first 17 items of the 28-item HMAD at both time of screening and after one week of placebo washout, with a drop of not more than 20 per cent over the week of placebo washout.

 

Patients were excluded for the following:

·         Predisposition to seizures, either by personal or family history, or by concurrent brain tumor or seizure-threshold-lowering medications

·         Presence of a significant DSM-III-R Axis II diagnosis that would suggest non-responsiveness to pharmacotherapy for depression.

·         History of diagnosis of anorexia nervosa or bulimia

·         Presence of medical disorder that would interfere with drug levels or with the accurate assessment of depression

 

 

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