PAREXEL International is a multinational contract research organization , based in Waltham, Massachusetts and founded in 1982 by Josef H. von Rickenbach and Anne Sayigh. It provides services for companies in the pharmaceutical, biotechnology and medical device industries, including consulting, clinical studies and market launch. The name PAREXEL comes from Paracelsus, a Swiss physician considered as the father of modern toxicology. PAREXEL employs more than 15,000 people worldwide in over 50 countries and has supported leading biotechnology companies and several large pharmaceutical companies to bring new drugs to the market.The company has been ranked to FlexJobs' list of 100 Top Companies for Remote Jobs in 2014.The company provides services during all phases of the development of a drug, from planning to commercialization. It includes strategy development, clinical trials management, data management, biostatistical analysis, regulatory affairs, drug development consulting, medical marketing, training, publishing and advanced eClinical technology solutions. Wikipedia.
Heelan B.T.,Parexel International
Human Vaccines and Immunotherapeutics | Year: 2014
Cancer vaccines are aimed at stimulating an immune response to tumor tissue. There is a high level of clinical activity in this rapidly advancing field with over 1,400 trials registered on Clincaltrials.gov. The recent approval of Sipuleucel-T which is the first cancer vaccine approved in the US and EU has encouraged developers in this field. In contrast to more established approaches for treating cancer such as chemotherapy, regulatory guidelines have been developed relatively recently for cancer vaccines. These guidelines advise on general clinical requirements. As there is an increase in innovative strategies with novel products, a 2-way dialog with regulators is recommended on a case-by-case basis to justify the clinical development plan, taking into account specific quality issues related to the product(s) in development. It is important that the rationale, background and justification for the planned development is convincing when interacting with the regulatory authorities, to enable drug developers and regulators to reach agreement. © 2014 Taylor & Francis Group, LLC.
A placebo-and midazolam-controlled phase i single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part I. safety, efficacy, and basic pharmacokinetics
Antonik L.J.,Johns Hopkins University |
Goldwater D.R.,Parexel International |
Kilpatrick G.J.,PAION UK Ltd. |
Tilbrook G.S.,PAION UK Ltd. |
Borkett K.M.,PAION UK Ltd.
Anesthesia and Analgesia | Year: 2012
BACKGROUND: A new benzodiazepine, remimazolam, metabolized by tissue esterases to an inactive compound, CNS 7054, has been developed to permit a fast onset, a short and more predictable duration of sedative action, and a more rapid recovery profile than with currently available benzodiazepines. We report on the safety and efficacy of the first human study. METHODS: A phase I, single-center, double-blind, placebo-and active-controlled, randomized, single-dose escalation study was conducted. Up to 10 cohorts of healthy subjects were scheduled to receive a single 1-minute IV infusion of remimazolam, midazolam, or placebo. In the 10 possible cohorts, remimazolam doses were from 0.01 to 0.35 mg/kg. In cohorts 1 to 3, 6 subjects received remimazolam and 1 placebo. From cohort 4 onward, an additional 3 subjects in each cohort received midazolam (0.075 mg/kg). Safety, pharmacokinetics, and pharmacodynamics were measured. A stop criterion of loss of consciousness for >5 minutes in >50% of subjects was predefined. RESULTS: The stop criterion was reached in cohort 9 (0.30 mg/kg remimazolam) so that 81 subjects were enrolled. Remimazolam was well tolerated in all dose cohorts, and no serious adverse events (AEs) were reported. Three AEs of mild (SpO2 85%-88%) hemoglobin desaturation (2 in the remimazolam groups and 1 in the midazolam group) resolved spontaneously, and 1 AE of moderate hemoglobin desaturation (SpO2 75%) resolved with a chin lift in the highest remimazolam dose group. No supplemental oxygen or manual ventilation was required. Vital signs remained stable throughout, although there was an increase in heart rate 2 minutes postdose for both remimazolam and midazolam. There were no reports of hypo-or hypertension. The pharmacokinetic behavior of remimazolam was linear and its systemic clearance approximately 3 times that of midazolam. Clearance was essentially independent of body weight. A rapid onset and dose-dependent sedation was observed after administration of remimazolam at 0.05 mg/kg and higher. Remimazolam (0.075 to 0.20 mg/kg) induced peak sedation levels similar to or higher than those achieved with midazolam (0.075 mg/kg). Median recovery times after approximately equieffective doses of remimazolam (0.10 and 0.15 mg/kg) and midazolam (0.075 mg/kg) were 10 and 40 minutes, respectively. CONCLUSIONS: Remimazolam provided sedation with rapid onset and offset, and was well tolerated. There was no supplemental oxygen or ventilation required. On the basis of these data, further studies on the potential utility of remimazolam for sedation/anesthesia are warranted. Copyright © 2012 International Anesthesia Research Society.
Butters D.J.,Parexel International
Cochrane database of systematic reviews (Online) | Year: 2010
The addition of a chemotherapy drug or drugs to an established regimen is one method used to increase the dose and intensity of treatment for metastatic breast cancer. To assess the effects of adding one or more chemotherapy drugs to an established regimen in women with metastatic breast cancer. We searched the Cochrane Breast Cancer Group's Specialised Register (to August 2009) using the codes for "advanced breast cancer" and "chemotherapy". This review is an update of the original Cochrane Review (Issue 3, 2006). Randomised trials with a first line regimen of at least two chemotherapy drugs compared to the same regimen plus the addition of one or more chemotherapy drugs in women with metastatic breast cancer. Two authors extracted data independently from published trials. We derived hazard ratios (HR) from time-to-event outcomes where possible, and used a fixed-effect model for meta-analysis. We analysed response rates as dichotomous variables and extracted toxicity data where available. We identified 17 trials reporting on 22 treatment comparisons (2674 patients randomised). Fifteen trials (20 treatment comparisons) reported results for tumour response and 11 trials (14 treatment comparisons) published time-to-event data for overall survival. There were 1532 deaths in 2116 women randomised to trials of the addition of a drug to the regimen and control (the regimen alone). There was no detectable difference in overall survival between these patients, with an overall HR of 0.96 (95% confidence interval (CI) 0.87 to 1.07, P = 0.47) and no significant heterogeneity. We found no difference in time to progression between these regimens, with an overall HR of 0.93 (95% CI 0.81 to 1.07, P = 0.31) and no significant heterogeneity. Addition of a drug to the regimen was favourably associated with overall tumour response rates (odds ratio 1.21, 95% CI 1.01 to 1.44, P = 0.04) although we observed significant heterogeneity for this outcome across the trials. Where measured, acute toxicities such as alopecia, nausea and vomiting and leucopenia were more common with the addition of a drug. The addition of one or more drugs to the regimen shows a statistically significant advantage for tumour response in women with metastatic breast cancer but the results suggest no difference in survival time or time to progression. The positive effect on tumour response was also associated with increased toxicity.
Rice J.B.,Analysis Group Inc. |
White A.G.,Analysis Group Inc. |
Birnbaum H.G.,Analysis Group Inc. |
Schiller M.,Analysis Group Inc. |
And 2 more authors.
Pain Medicine (United States) | Year: 2012
Objective. The objective of this study was to use administrative claims data to identify and analyze patient characteristics and behavior associated with diagnosed opioid abuse. Design. Patients, aged 12-64 years, with at least one prescription opioid claim during 2007-2009 (n=821,916) were selected from a de-identified administrative claims database of privately insured members (n=8,316,665). Patients were divided into two mutually exclusive groups: those diagnosed with opioid abuse during 1999-2009 (n=6,380) and those without a diagnosis for opioid abuse (n= 815,536). A logistic regression model was developed to estimate the association between an opioid abuse diagnosis and patient characteristics, including patient demographics, prescription drug use and filling behavior, comorbidities, medical resource use, and family member characteristics. Sensitivity analyses were conducted on the model's predictive power. Results. In addition to demographic factors associated with abuse (e.g., male gender), the following were identified as "key characteristics" (i.e., odds ratio [OR]>2): prior opioid prescriptions (OR=2.23 for 1-5 prior Rxs; OR=6.85 for 6+ prior Rxs); at least one prior prescription of buprenorphine (OR=51.75) or methadone (OR=2.97); at least one diagnosis of non-opioid drug abuse (OR=9.89), mental illness (OR=2.45), or hepatitis (OR=2.36); and having a family member diagnosed with opioid abuse (OR=3.01). Conclusions. Using medical as well as drug claims data, it is feasible to develop models that could assist payers in identifying patients who exhibit characteristics associated with increased risk for opioid abuse. These models incorporate medical information beyond that available to prescription drug monitoring programs that are reliant on drug claims data and can be an important tool to identify potentially inappropriate opioid use. © Wiley Periodicals, Inc.
Edan G.,University of Rennes 1 |
Edan G.,University of Basel |
Edan G.,Ottawa Hospital Research Institute |
Edan G.,Heinrich Heine University Dusseldorf |
And 2 more authors.
Journal of neurology, neurosurgery, and psychiatry | Year: 2014
OBJECTIVE: To examine the long-term impact of early treatment initiation of interferon beta-1b (IFNB1b, Betaferon/Betaseron) in patients with a first event suggestive of multiple sclerosis (MS).METHODS: In the original placebo-controlled phase of BENEFIT, patients were randomised to IFNB1b 250 μg or placebo subcutaneously every other day. After 2 years or diagnosis of clinically definite MS (CDMS), all patients were offered open-label IFNB1b treatment for a maximum duration of 5 years. Thereafter, patients were enrolled in an observational extension study for up to 8.7 years.RESULTS: Of the initial 468 patients, 284 (60.7%; IFNB1b: 178 (61.0% of the original arm), placebo: 106 (60.2% of original arm)) were enrolled in the extension study. 94.2% of patients were receiving IFNB1b. Patients originally randomised to IFNB1b had a reduced risk of developing CDMS by 32.2% over the 8-year observation period (HR 0.678; 95% CI 0.525 to 0.875; p=0.0030), a longer median time to CDMS by 1345 days (95% CI 389 to 2301), and a lower annualised relapse rate (0.196 (95% CI 0.176 to 0.218) versus 0.255 (95% CI 0.226 to 0.287), p=0.0012), with differences mainly emerging in the first year of the study. Cognitive outcomes remained higher in the early treated patients. EDSS remained low over time with a median of 1.5 in both arms.CONCLUSIONS: These 8-year results provide further evidence supporting early initiation of treatment with IFNB1b in patients with a first event suggestive of MS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.