-- Relative bioavailability was assessed in 40 patients randomized to naltrexone SR 40mg or naltrexone immediate release (IR) 36mg in a single dose, crossover PK assessment. Analyses revealed that, on a dose-normalized basis, naltrexone SR was associated with a 43.3% lower peak concentration but a comparable exposure or area-under-the-curve (AUC) to the IR formulation. The Tmax or time to peak concentration was approximately 36 minutes slower for naltrexone SR compared to naltrexone IR.
-- Preliminary evidence for improved tolerability with naltrexone SR came from a trial utilizing a multiple dose, parallel design in 60 healthy volunteers randomized to either naltrexone SR 37.5mg / bupropion SR 270mg or naltrexone IR 36mg / bupropion SR 270mg. Patients were treated for up to 14 days. Naltrexone SR / bupropion SR patients spontaneously reported fewer GI adverse events (10.3% vs. 16.7%) or CNS adverse events (10.3% vs. 23.3%). GI event severity was also subjectively lowered with the naltrexone SR formulation.
-- In a preliminary effort to evaluate apparent improvements in
tolerability associated with naltrexone SR, pooled 24 week data from the
Phase 2 NB-201 Contrave trial (N=212) with naltrexone IR was compared with
the 24 week blinded data from a series of four Phase 3 Contrave trials
(N=3,943 evaluable patients), all employing naltrexone SR. These Phase 3
trials all have varying designs, doses and patient populations; the
discontinuation due to adverse event rates associated with them ranged from
13.8% to 22.8%. However, compared to the Phase 2 trial experience, lower
rates of nausea were evident across the four pooled Phase 3 trials. In
study NB-301 (N=1,689 evaluable patients), the trial with dosing most
similar to the Phase 2 NB-201 trial, nausea, headache, or dizziness were
all less frequent than in the prior Phase 2 trial, as was the overall rate
of early discontinuation due to any a
|SOURCE Orexigen Therapeutics, Inc.|
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