Folks,
more worthwhile stuff from healthcg's reporting from Geneva. This time on Viracept BID. When the rubble and debris are cleared away from the wreckage of Geneva, AGPH will still be plugging away, selling their product, building their business ...
Key quotes:
the walkaway quote:
"As
compliance with combination antiretroviral therapy regimens is a major
determinant of long-term success, subsequent nelfinavir-containing
regimens should be based on BID dosing of this agent. "
based on:
"BID and TID nelfinavir regimens provide
equally potent suppression of plasma HIV RNA with approximately 80% of
patients achieving viral loads of less 400 copies/mL. Of those patients
who responded, approximately 90% remain "undetectable" after up to 48
weeks of nelfinavir therapy. Pharmacokinetic analyses support the
concept of a BID dosing regimen. No increased adverse events seem to be
associated with the BID dosing schedule."
healthcg.com
/* section on Viracept BID
Five Big Blue Ones Twice a Day Just as Good as Three Thrice Daily
Forty-eight week results comparing BID and TID dosing of nelfinavir (in
combination with 3TC+d4T) were presented from the European Nelfinavir
Clinical Trial Group here today [1]. Patients included in this trial had
to have less than 6 months of any previous antiretroviral therapy, be
naive to either 3TC or d4T (later amended to be mandatorily naive to
3TC) and have less than two weeks of prior protease inhibitor therapy.
The rationale for the study was based upon nelfinavir's well-known
3.5-5.0 hour half life which theoretically should allow for BID dosing.
This study evaluated both pharmacokinetic (q8 hours vs. q12 hour steady
state dosing) and clinical antiretroviral activity of the approved 750
mg TID and a 1250 mg BID dosing schedule. (The original study design
included a 750 and a 1000 mg BID dosing schedule but was amended in
11/97 and all study participants in those 2 dosing arms were collapsed
into the 1250 mg BID dosing group.)
Preliminary results from 288 patients included in this analysis with up
to 48 weeks of follow-up showed mean change in HIV RNA from baseline of
2.2 log for the BID group vs. 2.4 log for the TID group. Eighty percent
of the patients in each group achieved plasma HIV viral loads below 400
copies/mL and approximately 60% in each group achieved plasma HIV viral
loads less than 50 copies/mL. CD4+ T cell count changes at week 48 were
+189 cells/mm3 and +166 cells/mm3 for the BID and TID groups,
respectively.
The most serious adverse events were reported: 4 patients discontinued
from the BID group due to adverse events: 2 due to rash and 2 due to
diarrhea. Overall, 9 (11.8%) of the TID patients and 27 (12.7%) of the
BID patients reported moderate to severe diarrhea. No adverse events
resulted in discontinuation of therapy in the TID group. Two patients in
each group were discontinued from the study due to treatment failure -
defined as two consecutive plasma HIV RNA measurements above 10,000
copies/L in previous responders. Adherance was reported to be good, with
only two patients in each group discontinuing treatment for
non-adherence reasons. One patient in the BID group was reported to
develop hyperglycemia judged possibly related to nelfinavir after 12
weeks of study therapy.
Plasma pharmacokinetics demonstrated median steady-state AUC for the
1250 mg BID regimen to be 51 mgxh/L vs. 45 mgxh/L for the 750 mg TID
group. The Cmin for both groups was approximately 0.5 micrograms/mL.
The authors concluded that the BID and TID nelfinavir regimens provide
equally potent suppression of plasma HIV RNA with approximately 80% of
patients achieving viral loads of less 400 copies/mL. Of those patients
who responded, approximately 90% remain "undetectable" after up to 48
weeks of nelfinavir therapy. Pharmacokinetic analyses support the
concept of a BID dosing regimen. No increased adverse events seem to be
associated with the BID dosing schedule.
These data provide immediately clinically useful information for
simplifying nelfinavir containing regimens, allowing patients to switch
or to be begun on 1250 mg BID dosing regimens. It is anticipated that
this change in regimen will enhance compliance in that it will coincide
with the dosing of the most commonly used RTIs such as AZT, 3TC, d4T and
nevirapine. The lack of difference in adverse events between the TID and
BID regimens also recommends this change in dosing as well. As
compliance with combination antiretroviral therapy regimens is a major
determinant of long-term success, subsequent nelfinavir-containing
regimens should be based on BID dosing of this agent. |
