Orexigen(R) Therapeutics Presents Data on Its Proprietary Formulation of Naltrexone Sustained Release (SR) Used in C...(ries of studies was conducted to validat...),Health

-- 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
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