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Durham, NC, United States

Katz N.,Analgesic Solutions | Katz N.,Tufts University | Kopecky E.A.,Collegium Pharmaceutical, Inc. | O'Connor M.,Collegium Pharmaceutical, Inc. | And 2 more authors.
Pain | Year: 2015

Opioid analgesics are commonly used for the treatment of chronic low back pain (CLBP); however, abuse potential is a major concern. This study used a randomized, double-blind, placebo-controlled, enriched-enrollment randomized-withdrawal study design to evaluate the safety, tolerability, and analgesic efficacy of an abuse-deterrent formulation of extended-release oxycodone, Xtampza ER, in opioid-naive and opioid-experienced adults with moderate-to-severe CLBP. Patients entered an open-label titration phase (N 740); those who were successfully titrated on Xtampza ER (≥40 to ≤160 mg oxycodone hydrochloride equivalent per day) were randomized to active drug (N 193) or placebo (N 196) for 12 weeks. Primary efficacy results showed a statistically significant difference in average pain intensity from randomization baseline to treatment week 12 between the Xtampza ER and placebo groups (mean [±SE],-1.56 [0.267]; P < 0.0001). All sensitivity analyses results supported the primary result of the study. Secondary efficacy outcomes indicated that Xtampza ER vs placebo had more patients with improvement in patient global impression of change (26.4% vs 14.3%; P < 0.0001), longer time-to-exit from the study (58 vs 35 days; P 0.0102), and a greater proportion of patients with ≥30% (49.2% vs 33.2%; P 0.0013) and ≥50% (38.3% vs 24.5%; P 0.0032) improvement in pain intensity. There was less rescue medication (acetaminophen) use in the Xtampza ER treatment group than in the placebo group. Xtampza ER had an adverse event profile consistent with other opioids and was well tolerated; no new safety concerns were identified. In conclusion, Xtampza ER resulted in clinically and statistically significant efficacy in patients with CLBP. © 2015 International Association for the Study of Pain.

Ephross S.A.,Glaxosmithkline | Sinclair S.M.,University of North Carolina at Wilmington | Sinclair S.M.,INC Research
Headache | Year: 2014

Objectives To monitor for a signal of major teratogenicity by determining the risk of all birth major defects following in utero exposure to sumatriptan, naratriptan, and the sumatriptan/naproxen sodium combination product (tablets marketed in the United States as Treximet [GlaxoSmithKline, Research Triangle Park, NC, USA]), and to monitor for unusual patterns of defects that might suggest teratogenicity. Background The prevalence of migraine is highest in women of childbearing age. Coupled with the recurrent nature of migraine attacks and the high proportion of unplanned pregnancies, intentional and inadvertent exposure to anti-migraine drugs in pregnancy is likely. The Sumatriptan, Naratriptan, and Treximet Pregnancy Registry captured data on women exposed to those drugs during pregnancy to monitor for evidence of major teratogenicity. Methods In this primarily prospective, observational study, health care professionals from anywhere in the world enrolled, on a voluntary basis, women exposed to sumatriptan, naratriptan, or the sumatriptan/naproxen sodium combination product during their pregnancies. Only pregnancies with unknown outcomes at the time of enrollment were included in the analysis. The proportion of infants or fetuses with major birth defects was calculated as the total number of infants/fetuses with major birth defects divided by the sum of the number of infants/fetuses with major birth defects+the number of live births without defects. The risk of major birth defects was further stratified by earliest trimester of pregnancy exposure. Results The registry enrolled 680 evaluable exposed pregnant women, which resulted in 689 infants and fetuses (outcomes). Of these outcomes, 626 were exposed to sumatriptan, 57 were exposed to naratriptan (seven were exposed to both sumatriptan and naratriptan), and six were exposed to the sumatriptan/naproxen sodium combination product. Twenty outcomes with major birth defects were reported among 528 outcomes exposed in the first trimester to sumatriptan. The estimated risk of major birth defects following first-trimester sumatriptan exposure is 4.2% (20/478 [95% confidence interval [CI] 2.6%-6.5%]). Among 52 first-trimester exposures to naratriptan, major birth defects were reported in one outcome, an infant with exposure to both sumatriptan and naratriptan [birth defect risk of 2.2% (1/46 [95% CI 0.1%-13.0%]). No major defects were reported among the five outcomes with first-trimester exposure to the sumatriptan/naproxen sodium combination products. Conclusions The Sumatriptan, Naratriptan, and Treximet Pregnancy Registry detected no signal of teratogenicity associated with major birth defects for sumatriptan. This finding is consistent with results from other observational studies using a variety of control groups. Enrollment in the registry was insufficient to permit definitive conclusions of the risks associated with naratriptan or sumatriptan/naproxen sodium tablets, or to assess the risk of individual birth defects in any of the products studied. Low enrollment and high rates of loss to follow up within the registry over an extended period of time led the registry's scientific advisory committee to conclude that continuation of the registry beyond its 16 years would offer little additional power to rule out more moderate increases in the risk of birth defects. Data from the other ongoing surveillance sources constitute an important element of post-marketing surveillance of these medications. The lack of a signal of major teratogenicity with sumatriptan across these several sources of data is encouraging. © 2014 American Headache Society.

Petrucci M.T.,University of Rome La Sapienza | Giraldo P.,University of Zaragoza | Corradini P.,University of Milan | Teixeira A.,University of Coimbra | And 8 more authors.
British Journal of Haematology | Year: 2013

Multiple myeloma (MM) typically follows a relapsing course with many patients requiring multiple therapies. This single-arm phase 2 study prospectively evaluated the efficacy and safety of bortezomib retreatment in MM patients who had relapsed after achieving at least a partial response (≥PR) to prior bortezomib-based therapy. Patients aged ≥18years, with measurable, secretory MM, who relapsed ≥6months after prior bortezomib treatment were eligible. Patients received up to eight cycles of bortezomib (±dexamethasone). The primary endpoint was best confirmed response at retreatment; secondary endpoints included duration of response (DOR), time to progression (TTP), and safety. Adverse events (AEs) were graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. A total of 130 patients (median of two prior lines of therapy) were enrolled and received retreatment. At retreatment, 28% and 72% of patients received bortezomib and bortezomib-dexamethasone, respectively. Overall response rate was 40%. In patients who achieved ≥PR, median DOR and TTP were 6·5 and 8·4months, respectively. Thrombocytopenia was the most common grade ≥3 AE (35%). Forty percent of patients experienced neuropathy events, which improved and resolved in a median of 1·5 and 8·9months, respectively. In conclusion, bortezomib retreatment was effective and tolerable in relapsed MM patients, with no evidence of cumulative toxicities. © 2013 Blackwell Publishing Ltd.

Objectives: Treatment of complicated skin and skin structure infections (cSSSIs) requires therapy that is effective against a range of Gram-positive and Gram-negative bacteria, including resistant pathogens such as methicillin-resistant Staphylococcus aureus. Equally important is the need to provide therapy that is safe and well tolerated. Ceftaroline fosamil is a new-generation, parenteral cephalosporin that was developed for the treatment of moderate to severe bacterial infections, including cSSSIs. This report provides an integrated safety summary of the CeftAroliNe Versus VAncomycin in Skin and Skin Structure Infections (CANVAS) 1 and 2 studies (registration numbers NCT00424190 and NCT00423657). Methods: Adult patients with cSSSIs requiring intravenous therapy received 600 mg of ceftaroline fosamil every 12 h or 1 g of vancomycin plus 1 g of aztreonam every 12 h for 5-14 days (randomized 1: 1). All patients were followed for treatment-emergent adverse events (TEAEs) occurring from the start of the initial study drug infusion up to the test-of-cure visit, ~1 week following the last dose of study medication; serious adverse events (SAEs) that occurred within 30 days after the last dose were recorded. Results: A total of 1378 patients received any amount of study drug and were included in the safety analysis. The percentage of patients with an SAE was similar between the ceftaroline fosamil and the vancomycin plus aztreonam groups (4.3% versus 4.1%). The majority of patients (>75%) had either no or mild TEAEs and the distribution of TEAEs based on severity was comparable between the groups. The most commonly reported TEAEs in patients treated with ceftaroline fosamil included nausea (5.9%), headache (5.2%), diarrhoea (4.9%) and pruritus (3.5%). Conclusions: Ceftaroline fosamil was well tolerated and did not result in any unexpected safety concerns. The data from the CANVAS trials suggest that ceftaroline fosamil has the expected safety and tolerability profile common to the cephalosporin class. © The Author 2010. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Coyle P.K.,Comprehensive Care | Sinclair S.M.,University of North Carolina at Wilmington | Scheuerle A.E.,Tesserae Genetics | Thorp Jr. J.M.,University of North Carolina at Chapel Hill | And 2 more authors.
BMJ Open | Year: 2014

Objective: Women with multiple sclerosis are often diagnosed and treated during their reproductive years. Limited data are available on the safety of treatment during pregnancy. The Betaseron Pregnancy Registry prospectively monitored women exposed to interferon β-1b (IFNβ-1b) during pregnancy to estimate the rates of birth defects, spontaneous abortions (SABs) and other negative outcomes in this population. Design: From 2006 to 2011, this observational registry enrolled women exposed prior to conception or during pregnancy (but prior to or without abnormalities on prenatal screening). Follow-up continued from enrolment through the 4-month paediatric visit. Setting: Patients in the USA who met these criteria were enrolled in the registry. Results: The registry enrolled 99 pregnant women; 3 were lost to follow-up. The earliest exposure to IFNβ-1b occurred during the first trimester for 95 pregnancies and in the third trimester for 1 pregnancy. There were 99 birth outcomes (3 twins), including 86 (86.9%) live births, 11 (11.1%) SABs and 2 (2%) stillbirths. Birth defects were reported in five (5.1%) cases. Rates of birth defects and SAB were not significantly different from population comparators. No developmental concerns were identified at the 4-month paediatric visit. Conclusions: The small sample size limits the ability to draw definitive conclusions; however, there was no pattern to suggest increased negative outcomes with IFNβ-1b. Clinical trials registration number: NCT00317564.

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