B. Discussions with the
Division about the NDA Submission
On
June 11, 2002, the sponsor presented its WELLBUTRIN XL development program to
the Division. The Division agreed with
the proposal to submit an NDA for WELLBUTRIN XL that would be based on data
demonstrating bioequivalence of the extended-release formulation of bupropion
and the immediate-release formulation [NDA 18,64] [NDA
18,644], (similar to the submission which formed the basis for approval
of WELLBUTRIN SR ([NDA 20, 358]). The
Division requested that the sponsor use Cmax, AUC, and Cmin as primary
parameters for determining steady-state bioequivalence and that these be
determined for bupropion, hydroxy-bupropion, threohydro-bupropion, and
erythrohydro-bupropion. In light of the
multiplicity of parameters to be used in the assessment of bioequivalence, an
additional measure of bioequivalence, the pharmacological activity-weighted
composite (PAWC) of bupropion and its metabolites, was recommended by the
Division. This parameter was used for
the approval of WELLBUTRIN SR, since > 90% of systemic drug exposure
involves metabolites rather than parent drug.
In addition, the PAWC was noted by the Division as being potentially
important in evaluating bioequivalence if one of the 12 individual parameters
to be evaluated differed slightly from those of the reference product.
C. Foreign Marketing History
No applications for
marketing approval of WELLBUTRIN XL have been submitted outside the U.S.
III. Clinically Relevant Findings
from Chemistry, Biopharmaceutics
These will be analyzed and reported by reviewers from the respective disciplines.
IV.
Safety Analysis of WELLBUTRIN XL
A. Description of Clinical Data and Sources
Safety
information reviewed included: 1) individual study reports from the
bioavailability studies (2543, 2544, 2548, 2571,
and 2526); and 2) case report forms from the 3 ongoing clinical trials
using WELLBUTRIN XL. Two of these
trials involve treatment of Seasonal Affective Disorder (AK 130930 &
AK 130936), and one involves the treatment of Attention Deficit
Hyperactivity Disorder in Adults (AK 130930).
2
Back a Page
Next Page
Back to Wellbutrin XL NDA Index Page
Back to Main Index Page