Kendle International Inc.

Durham, NC, United States

Kendle International Inc.

Durham, NC, United States
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Cunnington M.C.,Glaxosmithkline | Weil J.G.,Glaxosmithkline | Messenheimer J.A.,Glaxosmithkline | Ferber S.,Kendle International Inc. | And 2 more authors.
Neurology | Year: 2011

Objective: To monitor for a signal for major teratogenicity following in utero lamotrigine exposure. Methods: Health care providers reported lamotrigine exposure during pregnancy, and subsequent outcomes, on a voluntary basis. Prospective reporting early in pregnancy was encouraged. Major congenital malformations (MCMs) were classified according to the Centers for Disease Control and Prevention (CDC) criteria and were reviewed by a pediatrician on the Registry's Scientific Advisory Committee. The proportion of infants with MCMs was calculated by trimester and therapy type and descriptively compared to population-based reference estimates. Results: Over an 18-year period, 35 infants with MCMs were observed among 1,558 first-trimester monotherapy exposures: 2.2% (95% confidence interval [CI] 1.6%-3.1%). This was similar to estimates from general population-based cohorts. The observed proportion of infants with MCMs among 150 lamotrigine/valproate polytherapy exposures was 10.7% (95% CI 6.4%-17.0%) and was 2.8% (95% CI 1.5%-5.0%) among 430 infants exposed to lamotrigine polytherapy without valproate. No consistent pattern of malformation type, or malformation frequency by dose, was observed. DISCUSSION:: The Registry did not detect an appreciable increase in MCM frequency following first-trimester lamotrigine monotherapy exposure. With over 1,500 first-trimester monotherapy exposures, the Registry was powered to detect major teratogenicity. The proportion of infants with MCMs following lamotrigine/valproate polytherapy exposure was high, but similar to that previously reported with valproate monotherapy. The Registry failed to observe an increased MCM frequency with increasing lamotrigine dose. Monitoring of specific malformations among lamotrigine-exposed pregnancies will continue through case-control surveillance in the European Congenital Anomalies and Twins Registers network. © 2011 by AAN Enterprises, Inc. All rights reserved.

News Article | February 19, 2017

File Photo: Former Perella Weinberg investment banker Sean Stewart exits the Manhattan federal court house in New York City, U.S. on July 27, 2016. REUTERS/Brendan McDermid/File Photo NEW YORK (Reuters) - A former Wall Street investment banker was sentenced to three years in prison on Friday after he was convicted of engaging in insider trading by repeatedly tipping his father off to unannounced healthcare mergers. Sean Stewart, who worked at Perella Weinberg Partners and JPMorgan Chase & Co, was sentenced by U.S. District Judge Laura Taylor Swain in Manhattan, who called his conduct "outrageous." "He chose personal convenience, appearances and family benefits over the ethical obligations he had to his employers," Swain said. Stewart, who at trial contended his father, Robert Stewart, traded without his knowledge based on their discussions about his work, in court acknowledged breaching his employers' trust to keep details about deals secret. "In my heart and in my mind, though, I know I did not commit a crime," Stewart said. "I know that to be true. I do know, however, that I made very serious mistakes." Swain also sentenced Stewart, 35, to serve one year of home detention following his release from prison, and she ordered him to pay a $7,500 fine. Stewart is expected to appeal. Jurors had found Stewart guilty last August of securities fraud and other charges, making him one of 85 people to be convicted in a wave of insider trading cases by Manhattan U.S. Attorney Preet Bharara's office since 2009. Prosecutors said that from 2011 to 2014, Stewart tipped his father about five mergers, including INC Research LLC's [INCRR.UL] acquisition of Kendle International Inc. [nL1N1AY0Q9] "This was protracted and brazen conduct propped up by lies," Assistant U.S. Attorney Sarah Eddy said in court. Robert Stewart, a Long Island accountant, in some instances arranged for a friend, Richard Cunniffe, to conduct trades in his own accounts because of concern he was too close to the source, prosecutors said. The trading enabled the elder Stewart and Cunniffe to make $1.16 million, prosecutors said. At trial, Sean Stewart's lawyers acknowledged he spoke with his father about companies involved in mergers. But they said he did so while talking about his work, and that Robert Stewart betrayed his son by trading on the information. Robert Stewart was sentenced in May 2016 to a year of home detention after pleading guilty in August 2015. [nL2N1801TM] Cunniffe pleaded guilty in May 2015 and became a cooperating government witness. He is scheduled to be sentenced in July. The case is U.S. v. Stewart, U.S. District Court, Southern District of New York, No. 15-cr-00287.

Roberts S.S.,University of North Carolina at Wilmington | Roberts S.S.,Kendle International Inc. | Miller R.K.,University of Rochester | Jones J.K.,Degge Group Ltd. | And 7 more authors.
Birth Defects Research Part A - Clinical and Molecular Teratology | Year: 2010

INTRODUCTION: Ribavirin, with interferons or pegylated interferons, is used to treat chronic hepatitis C. Ribavirin is contraindicated in pregnancy (FDA Pregnancy Category X) and in men whose partners may become pregnant. In 2003, the Ribavirin Pregnancy Registry was established to monitor pregnancy exposures to ribavirin and to evaluate the potential human teratogenicity of prenatal exposure. METHODS: This voluntary registry enrolls pregnant women who have been exposed to ribavirin during pregnancy or during the six months prior to conception either directly, by taking ribavirin, or indirectly through sexual contact with a man taking ribavirin. Women are followed until delivery; live born infants are followed for one year. The Registry aims to enroll 131 live births following direct (maternal) exposure to ribavirin and 131 live births following indirect (male) exposures. RESULTS: After more than five years of operation, the Registry has enrolled 49 live births with direct exposure and 69 live births following indirect exposure. Six outcomes with birth defects have been reported. All were among live born infants: torticollis (2), hypospadias (1), polydactyly and a neonatal tooth (1), glucose-6-phosphate dehydrogenase deficiency (1), ventricular septal defect and cyst of 4th ventricle of the brain (1). Three received direct exposures ([6.1% (95% CI: 1.2, 16.9)], three were exposed indirectly [4.3% (95% CI: 0.9, 12.2)]. CONCLUSIONS: Although current enrollment is far short of the required sample size, preliminary findings have not detected a signal indicating human teratogenicity for ribavirin. However, findings must be interpreted with caution concerning direct or indirect prenatal ribavirin exposures. © 2010 Wiley-Liss, Inc.

Abulkhair O.,King Saud bin Abdulaziz University for Health Sciences | Al Tahan F.,King Saud bin Abdulaziz University for Health Sciences | Young S.,King Saud bin Abdulaziz University for Health Sciences | Musaad S.,Kendle International Inc. | Jazieh A.-R.,King Saud bin Abdulaziz University for Health Sciences
Annals of Saudi Medicine | Year: 2010

Background and Objectives: Despite its relatively low incidence in Saudi Arabia, breast cancer has been the most common cancer among Saudi females for the past 12 consecutive years. The objective of this study was to report the results of the first national public breast cancer screening program in Saudi Arabia. Methods: Women 40 years of age or older underwent breast cancer screening. Mammograms were scored using the Breast Imaging-Reporting and Data System (BI-RADS). Correlations between imaging findings, risk factors and pathological findings were analyzed. Results: Between September 2007 and April 2008, 1215 women were enrolled. The median age was 45 years, and median body mass index was 31.6 kg/m 2. Sixteen cases of cancer were diagnosed. No cancer was diagnosed in 942 women with R1/R2 scores, and only 1 case of cancer was diagnosed in 228 women with R0/R3 scores. However, among 26 women with R4/R5 scores, 50% had malignant disease and 35% had benign lesions. No correlation was found between known risk factors and imaging score or cancer diagnosis. Conclusions: Public acceptance of the breast cancer screening program was encouraging. Longitudinal follow-up will help in better determining the risk factors relevant to our patient population.

Guo J.J.,University of Cincinnati | Pandey S.,Kendle International Inc. | Doyle J.,Columbia University | Doyle J.,Center for Socioeconomic Research | And 3 more authors.
Value in Health | Year: 2010

Objective: Although regulatory authorities evaluate the risks and benefits of any new drug therapy during the new drug-approval process, quantitative risk-benefit assessment (RBA) is not typically performed, nor is it presented in a consistent and integrated framework when it is used. Our purpose is to identify and describe published quantitative RBA methods for pharmaceuticals. Methods: Using MEDLINE and other Internet-based search engines, a systematic literature review was performed to identify quantitative methodologies for RBA. These distinct RBA approaches were summarized to highlight the implications of their differences for the pharmaceutical industry and regulatory agencies. Results: Theoretical models, parameters, and key features were reviewed and compared for the 12 quantitative RBA methods identified in the literature, including the Quantitative Framework for Risk and Benefit Assessment, benefit-less-risk analysis, the quality-adjusted time without symptoms and toxicity, number needed to treat (NNT), and number needed to harm and their relative-value-adjusted versions, minimum clinical efficacy, incremental net health benefit, the risk-benefit plane (RBP), the probabilistic simulation method, multicriteria decision analysis (MCDA), the risk-benefit contour (RBC), and the stated preference method (SPM). Whereas some approaches (e.g., NNT) rely on subjective weighting schemes or nonstatistical assessments, other methods (e.g., RBP, MCDA, RBC, and SPM) assess joint distributions of benefit and risk. Conclusions: Several quantitative RBA methods are available that could be used to help lessen concern over subjective drug assessments and to help guide authorities toward more objective and transparent decision-making. When evaluating a new drug therapy, we recommend the use of multiple RBA approaches across different therapeutic indications and treatment populations in order to bound the risk-benefit profile. © 2010, International Society for Pharmacoeconomics and Outcomes Research (ISPOR).

Lu K.,Merck And Co. | Jiang L.,Kendle International Inc. | Tsiatis A.A.,North Carolina State University
Biometrics | Year: 2010

Often a binary variable is generated by dichotomizing an underlying continuous variable measured at a specific time point according to a prespecified threshold value. In the event that the underlying continuous measurements are from a longitudinal study, one can use the repeated-measures model to impute missing data on responder status as a result of subject dropout and apply the logistic regression model on the observed or otherwise imputed responder status. Standard Bayesian multiple imputation techniques (Rubin, 1987, in Multiple Imputation for Nonresponse in Surveys) that draw the parameters for the imputation model from the posterior distribution and construct the variance of parameter estimates for the analysis model as a combination of within- and between-imputation variances are found to be conservative. The frequentist multiple imputation approach that fixes the parameters for the imputation model at the maximum likelihood estimates and construct the variance of parameter estimates for the analysis model using the results of Robins and Wang (2000, Biometrika 87, 113-124) is shown to be more efficient. We propose to apply (Kenward and Roger, 1997, Biometrics 53, 983-997) degrees of freedom to account for the uncertainty associated with variance-covariance parameter estimates for the repeated measures model. © 2010, The International Biometric Society.

Sietsema W.K.,Kendle International Inc.
Methods in molecular biology (Clifton, N.J.) | Year: 2010

Standardization of the measurement of pain in clinical trials will reduce variability, thus improving the quality of the data and reducing the number of patients needed to conduct pain trials. Standardization applies to the physical and psychosocial environment surrounding the patient, and there are many elements within this environment that can be effectively controlled. For example, the appearance of the examination room can be selected for neutrality and influences from visitors and staff can be minimized. Training is an important aspect of the standardization process and should be provided to all study staff. Staff training should first provide orientation on the protocol objectives and procedures and then a thorough discussion of the pain measures being used and how assessments will be conducted. Furthermore, as the patient is ultimately responsible for assessing his or her level of pain, it is important to train the patient to make reliable and accurate assessments of pain.

Kendle International Inc. | Date: 2010-01-05

Computer program for identifying and selecting medical investigators in clinical trials.

PubMed | Kendle International Inc.
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

6598 Background: Talabostat (TAL) is an orally administered small molecule inhibitor of dipeptidyl peptidases such as CD26 and fibroblast activation protein (FAP) in bone marrow, lymph nodes, and stroma of solid tumors, and TAL induces cytokine and chemokines in lymph nodes and spleen. TAL enhances the activity of rituximab (RTX) in a mouse model of lymphoma. This study evaluates the efficacy of TAL + RTX in patients with advanced CLL who failed fludarabine (FLU) and/or RTX.Single-arm, open-label study of RTX 375mg/m40 patients (32 men, 8 women), median age 64.0 (range 42-83) have entered the study. Most (85%) are caucasian, and 78% of patients are Rai Stage IV. Mean serum B2 microglobulin is 6.5mg/L. The median number of prior regimens is 4 (range 1 to 10); 78% of patients received prior RTX and 33% prior alemtuzumab. Partial response (PR) has been reported in 8/36 evaluable patients (22%), 6 of whom had failed RTX; 3 of these patients had also failed alemtuzumab. Response duration currently ranges from 2 to 10 months (median 5.0 months). Most toxicities are Grade 1 or 2, and include nausea, fever (28% each), and edema (25%). Fever with associated Grade 3 or 4 neutropenia is reported in 2 and 1 patient, respectively. Other Grade 3 AEs include dyspnea (n=3), fatigue (n=2), and aspergillus pneumonia and a dermal fungal infection in 1 patient each. Grade 4 AEs are thrombocytopenia, hypoglycemia, and pulmonary embolism in 1 patient each. 4 patients died due to CLL (2 due to PD) or related complications (PE or MRSA pneumonia, 1 each).TAL + RTX shows promising activity in CLL patients with advanced disease who failed FLU and/or RTX. AEs are similar to those seen with RTX, with the exception of edema in 25% of patients. Updated results, including median PFS and survival will be presented at the annual meeting. [Table: see text].

PubMed | Kendle International Inc.
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

8040 Background: Talabostat (TAL) is an oral inhibitor of dipeptidyl peptidases such as fibroblast activation protein found on the stroma of tumors, draining lymph nodes, and in melanomas. TAL up-regulates cytokines and chemokines, leading to specific T-cell immunity and T-cell independent activity. TAL significantly enhances the activity of cisplatin (C) in mice, and reduces tumor size >60% in melanoma xenografts (A375, A2058). This trial evaluated the activity of TAL and C in patients with Stage IV melanoma.Open-label, single-arm, Phase 2 study of 4 x 3-week cycles of C-75mg/m74 patients (50 men, 24 women) entered the study; median age was 58 years (range 27 to 79); 94.6% were caucasian. Most patients (71.4%) were M1c, and the majority (64.3%) had received at least 1 prior regimen; 72.9% of these had received prior cytokine treatment. A PR was reported in 5/42 evaluable patients (11.9%), and SD for at least 4 cycles in an additional 21/42 (50%). Median PFS and survival are currently estimated at 2.6 months (95% CI 2.1, 3.4) and 8.5 months (95% CI 5.4, infinity), respectively in the ITT population. Most frequent AEs were nausea (46%), fatigue (35%), and vomiting (34%); the high unevaluability rate patients was due to non-compliance related to C-associated N/V (thus the dose of C was reduced mid-study from 100 to 75mg/mThe combination of TAL and C is active in patients with Stage IV melanoma. Most AEs were related to C-associated nausea and vomiting, limiting the oral delivery of TAL. Additional studies of TAL in melanoma with other drug combinations are warranted. [Table: see text].

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