CLINICAL
PHARMACOLOGY/BIOPHARMACEUTICS REVIEW
AMENDMENT
|
NDA: |
21-515 |
|
Sponsor: |
GlaxoSmithKline |
|
Drug: |
Extended
Release Tablets |
|
Proposed
Indication: |
Major
Depressive Disorder |
|
Material
Submitted: |
DSI
Inspection of Study AK1BIOVAIL2543 |
|
Correspondence
Date: |
August
26, 2002 |
|
Reviewer: |
Sally
Usdin Yasuda, MS, PharmD |
Background:
The
Office of Clinical Pharmacology and Biopharmaceutics requested a Division of
Scientific Investigations (DSI) inspection of the pivotal bioequivalence study
in this NDA submission. The clinical
and analytical portions of this study were conducted at Biovail Contract Research
in Toronto, Ontario, Canada. Due to the
SARs outbreak in Canada, the study documents were transported to Biovail
Technologies Ltd. in Chantilly, VA for regulatory review.
The
DSI found that the analytical report did not accurately reflect the source data
for subject 26, in which the erythrohydrobupropion (also referred to as
bupropion erythroamino alcohol) results were shifted several time points
beginning at the 7.5 hour time point on Day 13 of period 2 (Wellbutrin 100 mg
tid) and incorrectly transcribed to the analytical report. The DSI provided the actual concentrations.
Current Review:
These
correct data for period 2 for subject 26 were used by the Office of Clinical
Pharmacology and Biopharmaceutics to re-evaluate the bioequivalence comparison
for this metabolite. The Cmin
(corrected) is 80.9 (33) ng/ml and was preciously calculated as 85.6 (31)
ng/ml, (mean, CV). The AUC0-t (corrected)
is 2350.5 (28) ng*hr/ml and was previously calculated as 2353.7 (27) ng*hr/ml,
(mean, CV). There was no change in the
Cmax. These changes did not
result in any changes in the ratio of geometric means or the 90% confidence
interval for the ratio of geometric means, and therefore remain within the
bioequivalence interval of 0.8 to 1.25.
Note:
the [The] reviewer made a typographical error in
the original review in reporting the Cmax for bupropion erythroamino
alcohol (reference) as [blacked out] and it should have been [blacked
out]. This was a typographical
error in the report and did not affect the BE calculations.
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