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Freeman R.,Beth Israel Deaconess Medical Center | Wallace M.S.,University of California at San Diego | Sweeney M.,Depomed Inc. | Backonja M.M.,University of Wisconsin - Madison
Pain Medicine (United States) | Year: 2015

Objective: To determine the effect of gastroretentive gabapentin (G-GR) and describe relationships among pain quality, pain impact, and overall-improvement scores in patients with postherpetic neuralgia (PHN). Methods: Analyses of integrated data from two Phase 3 studies in which PHN patients received once-daily G-GR 1,800 mg (n=356) or placebo (n=363). Neuropathic pain scale (NPS) and brief pain inventory (BPI) were completed at baseline and Week 10; patients' global impression of change (PGIC) at Week 10. Regression analyses described relationships among changes in the NPS, BPI, and PGIC scores. Results: Compared with placebo, G-GR patients had significant reductions from baseline in individual NPS measures except cold pain (P < 0.05); composite NPS scores (P≤0.003); BPI pain scores (P<0.05); three individual (mood, sleep, and enjoyment of life) and the average of BPI interference scores (P < 0.05). Clinically significant improvements in BPI interference scores (except walking ability) were positively correlated with reductions in BPI and NPS pain (except dull and cold pain), and with improvements on the PGIC. Reductions in pain qualities at Week 2, especially in NPS pain intensity, were significant (P≤0.0001) predictors of improvements in three BPI interference scores, total NPS score, and PGIC. Conclusions: For patients with PHN, G-GR provided significant improvements in multiple measures of pain quality and pain-related functional impairment. There was a positive correlation between pain relief and improvement in patient function, with reduction in pain intensity among predictors of improvements in patients' lives. Such comprehensive analyses give an insight into numerous factors that may contribute to better management of PHN. © 2015 American Academy of Pain Medicine.

Fischer K.E.,University of California at San Francisco | Nagaraj G.,University of California at San Francisco | Hugh Daniels R.,Nanosys | Li E.,Nanosys | And 4 more authors.
Biomaterials | Year: 2011

Delivering therapeutics to mucosal tissues such as the nasal and gastrointestinal tracts is highly desirable due to ease of access and dense vasculature. However, the mucus layer effectively captures and removes most therapeutic macromolecules and devices. In previous work, we have shown that nanoengineered microparticles (NEMPs) adhere through the mucus layer, exhibiting up to 1000 times the pull-off force of an unmodified microsphere, and showing greater adhesion than some chemical targeting means. In this paper, we demonstrate that nanotopography improves device adhesion in vivo, increasing retention time up to ten-fold over unmodified devices. Moreover, we observe considerable adhesion in several cell lines using an in vitro shear flow model, indicating that this approach is promising for numerous tissues. We then demonstrate that nanowire-mediated adhesion is highly robust to variation in nanowire surface charge and cellular structure and function, and we characterize particle loading and elution. We present a form of cytoadhesion that utilizes the physical interaction of nanoengineered surfaces with subcellular structures to produce a robust and versatile cytoadhesive for drug delivery. These nanoscale adhesive mechanisms are also relevant to fields such as tissue engineering and wound healing because they likely affect stem cell differentiation, cell remodeling, migration, etc. © 2011 Elsevier Ltd.

Sang C.N.,Harvard University | Sathyanarayana R.,Depomed Inc. | Sweeney M.,Depomed Inc.
Clinical Journal of Pain | Year: 2013

OBJECTIVE:: To evaluate the safety and efficacy of a once-daily gastroretentive formulation of gabapentin (G-GR; 1800 mg). METHODS:: This was an 11-week, double-blind, randomized, placebo-controlled Phase 3 clinical trial in patients with postherpetic neuralgia. Patients underwent a 2-week dose titration, 8 weeks of stable dosing, and 1 week of dose tapering. The primary endpoint was the change in average daily pain intensity score from Baseline to Week 10 using Baseline Observation Carried Forward (BOCF) imputation. RESULTS:: Four-hundred and fifty-two patients (mean age 65.6 y, BMI 29 Kg/m) were randomized. Baseline average daily pain intensity score during the week prior to randomization was 6.6 and 6.5 for the G-GR and placebo treatment groups, respectively. Three hundred and seventy-seven patients completed the study (84% G-GR, 83% placebo). G-GR significantly reduced BOCF change in average daily pain intensity compared with placebo (-2.1 vs. -1.6; G-GR vs. placebo, P=0.013). Compared with placebo, more G-GR-treated patients reported "much" or "very much" improvement (patient global impression of change, 43% vs. 34%; P<0.0434), and G-GR reduced sleep interference (-2.3 vs. -1.59; P<0.0001), although neither endpoint was considered statistically significant based on a stringent hierarchical statistical paradigm. Other secondary endpoints showed similar trends. The most common adverse events were dizziness (G-GR, 11.3% vs. placebo, 1.7 %) and somnolence (G-GR, 5.4% vs. placebo, 3.0%). CONCLUSION:: Once-daily G-GR 1800 mg was effective and well tolerated for the relief of pain in patients with postherpetic neuralgia. Copyright © 2012 by Lippincott Williams & Wilkins.

Chen C.,Depomed Inc. | Gupta A.,Depomed Inc.
Pain management | Year: 2014

This review will provide an overview of pharmacokinetics and clinical practice considerations of the novel formulations of fentanyl for the treatment of breakthrough cancer pain. First, we provide a brief description of the physicochemical properties of fentanyl. Second, we describe the basic pharmacokinetics of fentanyl, the specifics of various formulations and how they affect pharmacokinetics of fentanyl. Finally, we offer the perspectives on clinical practices in the proper uses of these products. Advancements in the formulations and delivery of fentanyl have provided a safer and more effective treatment for breakthrough cancer pain. These dosage forms offer overlapping yet distinct pharmacokinetic advantages to allow more choices for physicians and patients in the management of breakthrough cancer pain.

Wallace M.S.,University of California at San Diego | Irving G.,Swedish Pain and Headache Center Washington | Cowles V.E.,Depomed Inc.
Clinical Drug Investigation | Year: 2010

Background: Postherpetic neuralgia (PHN) is a neuropathic pain syndrome that may develop subsequent to healing of herpes zoster rash. Objectives: This study aimed to determine the efficacy and safety of gabapentin extended-release (gabapentin ER) tablets for the treatment of patients with PHN and to determine whether optimal benefits might be achieved with once-daily (QD) or divided-dose (DD) administration.Methods: This was a 10-week, randomized, double-blind, placebo-controlled, multicentre trial comparing gabapentin ER (total daily dose 1800 mg) either QD or as an asymmetrical DD with placebo in 407 patients with post-zoster pain for ≥3 months and a baseline average daily pain score (ADP) ≥4 on a 010 Likert numerical rating scale. The primary efficacy outcome was the ADP score mean change from baseline to week 10 using baseline observation carried forward (BOCF). Secondary efficacy outcomes included changes to week 10 in last observation carried forward (LOCF) ADP score, LOCF average daily sleep interference score, Short-Form McGill Pain Questionnaire score, Neuropathic Pain Scale score, and Brief Pain Inventory score. Results: Of 407 randomized patients, 400 were included in the intent-to-treat population (gabapentin ER QD, n = 134; gabapentin ERDD, n = 135; placebo, n = 131). Between-group differences in the least squares (LS) mean changes in BOCF ADP scores did not reach statistical significance (gabapentin ER QD -1.85 [p = 0.110 vs placebo]; gabapentin ER DD -1.72 [p = 0.255 vs placebo]; placebo -1.42). In the LOCF analysis, the LS mean ADP score for the gabapentin ER QD group, but not for the DD group, improved compared with placebo (gabapentin ER QD, -2.28; p = 0.032 vs placebo). Improvements compared with placebo were also observed in the gabapentin ER QD group, but not for the DD group, for mean daily sleep interference scores (gabapentin ER QD, -2.49; placebo, -1.63; p < 0.001). Most adverse events (AEs) were mild or moderate. Among gabapentin-treated patients, 12% and 11% withdrew due to AEs, most commonly for dizziness (2% and 3%), in the gabapentin ER QD and DD groups, respectively. Treatment-related AEs in the gabapentin ER-treated groups occurred in 31% of patients. The most common AEs in the gabapentin ER QD and DD groups included dizziness (10% and 15%), headache (4% and 7%), somnolence (3% and 7%) and peripheral oedema (5% and 5%), respectively. Conclusion: The primary efficacy endpoint for this study of gabapentin ER was not met, most likely due to the unexpectedly large placebo response. Outcomes on secondary endpoints suggest the potential efficacy of gabapentin ER QD. Gabapentin ER was well tolerated in this study. © 2010 Adis Data Information BV. All rights reserved.

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