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7 results on '"Wadell, Cecilia"'

2. Disease-Modifying Effects of a Novel Cathepsin K Inhibitor in Osteoarthritis

Author

Conaghan, Philip G., primary, Bowes, Michael A., additional, Kingsbury, Sarah R., additional, Brett, Alan, additional, Guillard, Gwenael, additional, Rizoska, Biljana, additional, Sjögren, Niclas, additional, Graham, Philippa, additional, Jansson, Åsa, additional, Wadell, Cecilia, additional, Bethell, Richard, additional, and Öhd, John, additional

Published
2019
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4. Disease-Modifying Effects of a Novel Cathepsin K Inhibitor in Osteoarthritis: A Randomized Controlled Trial.

Author

Conaghan, Philip G., Bowes, Michael A., Kingsbury, Sarah R., Brett, Alan, Guillard, Gwenael, Rizoska, Biljana, Sjögren, Niclas, Graham, Philippa, Jansson, Åsa, Wadell, Cecilia, Bethell, Richard, and Öhd, John

Subjects
RANDOMIZED controlled trials, FEMUR, MAGNETIC resonance imaging, ANIMAL models in research, CARTILAGE
Abstract

Background: MIV-711 is a novel selective cathepsin K inhibitor with beneficial effects on bone and cartilage in preclinical osteoarthritis models.Objective: To evaluate the efficacy, safety, and tolerability of MIV-711 in participants with symptomatic, radiographic knee osteoarthritis.Design: 26-week randomized, double-blind, placebo-controlled phase 2a study with a 26-week open-label safety extension substudy. (EudraCT: 2015-003230-26 and 2016-001096-73).Setting: Six European sites.Participants: 244 participants with primary knee osteoarthritis, Kellgren-Lawrence grade 2 or 3, and pain score of 4 to 10 on a numerical rating scale (NRS).Intervention: MIV-711, 100 (n = 82) or 200 (n = 81) mg daily, or matched placebo (n = 77). Participants (46 who initially received 200 mg/d and 4 who received placebo) received 200 mg of MIV-711 daily during the extension substudy.Measurements: The primary outcome was change in NRS pain score. The key secondary outcome was change in bone area on magnetic resonance imaging (MRI). Other secondary end points included cartilage thickness on quantitative MRI and type I and II collagen C-telopeptide biomarkers. Outcomes were assessed over 26 weeks.Results: Changes in NRS pain scores with MIV-711 were not statistically significant (placebo, -1.4; MIV-711, 100 mg/d, -1.7; MIV-711, 200 mg/d, -1.5). MIV-711 significantly reduced medial femoral bone area progression (P = 0.002 for 100 mg/d and 0.004 for 200 mg/d) and medial femoral cartilage thinning (P = 0.023 for 100 mg/d and 0.125 for 200 mg/d) versus placebo and substantially reduced bone and cartilage biomarker levels. Nine serious adverse events occurred in 6 participants (1 in the placebo group, 3 in the 100 mg group, and 2 in the 200 mg group); none were considered to be treatment-related.Limitation: The trial was relatively short.Conclusion: MIV-711 was not more effective than placebo for pain, but it significantly reduced bone and cartilage progression with a reassuring safety profile. This treatment may merit further evaluation as a disease-modifying osteoarthritis drug.Primary Funding Source: Medivir. [ABSTRACT FROM AUTHOR]

Published
2020
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5. Predictors of severe pain in a cohort of 5271 individuals with self-reported neuropathic pain

Author

Butler, Stephen H., Jonzon, Bror, Branting-Ekenback, Christina, Wadell, Cecilia, Farahmand, Bahman, Butler, Stephen H., Jonzon, Bror, Branting-Ekenback, Christina, Wadell, Cecilia, and Farahmand, Bahman

Abstract

The influence of pain descriptors and mechanical hypersensitivity on pain severity in neuropathic pain has not been well researched and is poorly understood. The aim of this study was to determine the relationship between pain severity and other factors describing chronic neuropathic pain in a large cohort of patients with self-reported neuropathic pain potentially recruited as subjects for a Phase IIa study. A questionnaire specific to the study parameters covering demographics and pain characteristics was sent to potential participants. Overall, 9185 questionnaires were returned from potential subjects who self-reported neuropathic pain. Adjusted odds ratios with 95% confidence intervals were used as a measure of association. These were estimated by unconditional logistic regression. Pain descriptors in the questionnaire were: burning, shooting, shocking, and aching. The presence of self-reported allodynia and hyperalgesia was strongly indicative of both moderate and severe pain, with a significant interaction of both factors in moderate and severe pain. Having 3 or 4 pain descriptors was also strongly indicative of both moderate and severe pain. Female gender, age, and history of serious mental disorders were found to be weaker indicators of both moderate and severe pain. Given the large and varied population with many neuropathic pain diagnoses in the study, the findings are not likely to be merely chance, but are likely to reflect important relationships between pain severity and other factors in those who suffer from chronic neuropathic pain.

Published
2013
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6. Nasal Drug Delivery : In Vitro Studies on Factors Influencing Permeability and Implications on Absorption

Author

Wadell, Cecilia

Subjects
FARMACI, Pharmaceutical Sciences, otorhinolaryngologic diseases, Pharmacy, respiratory system, Farmaceutiska vetenskaper
Abstract

Nasal delivery is a feasible alternative to oral or parenteral administration for some drugs because of the high permeability of the nasal epithelium, rapid drug absorption across this membrane and avoidance of hepatic first-pass metabolism. The main objective of this thesis was to investigate factors influencing the permeability of the nasal mucosa to various compounds and to evaluate implications for drug absorption via the nasal route. Porcine nasal mucosa mounted in an Ussing chamber system was established as an in vitro model, and glucose, insulin, lidocaine, mannitol, melagatran, nicotine, PEG 4000, propranolol, sumatriptan, verapamil, vinblastine and an aminodiether were used as model compounds. The pharmacokinetics of melagatran and propiomazine were investigated in absorption studies in rats, and the influence of the enhancers SDS and EDTA on melagatran absorption was evaluated and compared with in vitro permeability data. The expression of P-glycoprotein in porcine nasal mucosa was investigated and compared with that in human nasal epithelial biopsies using the Western Blot technique. The results demonstrated that the Ussing chamber model using porcine nasal mucosa has potential as a tool for evaluating mechanisms of nasal absorption and predicting the in vivo effects of absorption enhancers. Moreover, porcine nasal mucosa is comparable to human nasal mucosa in its morphology and P-glycoprotein expression. The in vitro permeability data were found to weakly correlate with literature data on human absorption after nasal administration of the corresponding compounds. In vivo absorption studies of the sedative propiomazine demonstrated that nasal administration of this drug offers an interesting alternative to the oral formulation currently on the market, since the absorption was rapid and the bioavailability was promising. The bioavailability of melagatran in rats was moderate but variable, and responded to the addition of enhancers. Finally, the establishment and characterisation of an in vitro method for prediction of nasal drug absorption, and the investigation of factors influencing nasal membrane permeability and absorption offer substantial contributions for nasal drug delivery.

Published
2002

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