ABSTRACT
OBJECTIVE: To evaluate the effect of 32-mg/d naltrexone sustained release and 360-mg/d bupropion sustained release (NB32) in overweight and obese patients with major depressive disorder (MDD). METHOD: Twenty-five female patients with a DSM-IV diagnosis of MDD, an Inventory of Depressive Symptomatology-Self-Report score > 26, and a body mass index ≥ 27 and ≤ 43 kg/m(2) received up to 24 weeks of open-label treatment with NB32 with dietary and behavioral counseling (data collection: March 2008-July 2009). The primary endpoint was change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score at 12 weeks; secondary endpoints included MADRS total score at week 24, change in weight, and Clinical Global Impressions-Improvement scale responder status (CGI-I score ≤ 2) at weeks 12 and 24 (modified intent-to-treat [mITT]: patients with ≥ 1 postbaseline MADRS total score on study drug; N = 23). RESULTS: MADRS scores showed significant reductions at weeks 12 and 24 (mITT-last observation carried forward [LOCF]: -13.1 ± 7.1 and -15.3 ± 8.1, respectively, P < .001 vs baseline for all). Mean ± SD weight loss was -4.0% ± 4.6% (mITT-LOCF) and -6.1% ± 4.7% (observed cases) at week 12 and -5.3% ± 6.5% (mITT-LOCF) and -9.2% ± 6.2% (observed cases) at week 24 (P < .001 vs baseline for all). By week 24, 95% of patients (mITT-LOCF) were responders (CGI-I score ≤ 2) and 70% were in remission (CGI-I score = 1). The safety/tolerability profile of NB32 was consistent with its individual components; the most common adverse events were nausea, constipation, headache, and insomnia, with no serious adverse events attributed to NB32. CONCLUSION: Twenty-four weeks of open-label NB32 therapy with dietary and behavioral counseling was associated with improvement in depressive symptoms and reduced body weight in overweight/obese women with MDD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00624858.
ABSTRACT
OBJECTIVE: To compare the pharmacokinetics of the extended-release MMX® formulation of budesonide (Uceris®) with that of Entocort® EC, an extended (controlled ileal) release formulation of budesonide. METHODS: Using an open-label, randomized, three-period crossover, Latin square design, healthy male or female volunteers received single doses of 6 mg Uceris®, 9 mg Uceris® or 9 mg Entocort® EC. Standard pharmacokinetic parameters were assessed. RESULTS: The study included 12 subjects. The 9 mg Uceris® and 9 mg Entocort® EC formulations had comparable area under the concentration-time curve (AUC) data, but 9 mg Uceris® had a notably longer time to first appearance in plasma (median Tlag, 6 h versus 1 h, respectively), and a delayed time to maximum concentration (median Tmax, 15 h versus 5 h, respectively) compared with 9 mg Entocort® EC. The ratio of log-transformed AUC0-last (Uceris®/Entocort® EC) was 91% (90% confidence interval [CI] 77%, 108%) and the corresponding maximum concentration ratio was 79% (90% CI 63%, 100%). CONCLUSION: Uceris was associated with a similar extent (AUC) of systemic exposure to budesonide compared with that following Entocort. However, for Uceris, the pharmacokinetic profile was delayed, a pattern consistent with greater colonic delivery of the active substance.
