Clinical Research and Regulatory Affairs最新文献

{"title":"The pharmacodynamic equivalence of Orlistat 60 mg capsule. An open label, balanced, randomized, multiple-dose, cross-over pharmacodynamic end-point bioequivalence study in healthy, adult, human Asian Indian subjects under fed conditions","authors":"Sudershan Kumar, T. Monif, R. Arora, A. Khuroo, Rakesh K. Jain, S. Reyar, P. Verma, Shireen Rao","doi":"10.3109/10601333.2013.840311","DOIUrl":"https://doi.org/10.3109/10601333.2013.840311","url":null,"abstract":"Abstract Orlistat is a non-systemic treatment for obesity. The drug inhibits lipase in the gastrointestinal track mainly in the lumen of the stomach and small intestine by binding reversibly with the active site of gastric and pancreatic lipases, preventing the absorption of ∼30–35% of dietary fat. The undigested triglycerides are not absorbed, resulting in a caloric deficit and positive effect in weight control. The objective of this study was to assess the bioequivalence of orlistat administered as a generic and reference capsule formulations using a pharmacodynamic end-point. A total of 60 healthy volunteers followed a 5-day run-in diet period to be accustomed to a low fat diet; subjects were then randomized to receive under fed conditions oral doses of orlistat (60 mg) 3-times daily for 10 days as the generic (Ranbaxy Laboratories) or reference (Alli™, GlaxoSmithKline) capsule formulations. Subjects followed a standardized diet (2500 kcal/day, ∼30% as fat) for the entire study. Feces were collected over the last 2 days of the run-in period (baseline) and over the last 5 days of the two treatment periods. The amount of fat in meals and feces were assayed using the validated FTIR method with a limit of detection of 1.00 g%, respectively. Fecal fat excretion over 24 h (FFE24SS, calculated as the amount of fat excreted in feces adjusted by the amount of fat ingested) was used as a pharmacodynamic end-point to assess the bioequivalence between the two orlistat formulations. An analyses of variance (ANOVA) was performed on the log-transformed FFE24SS parameter to establish bioequivalence of the generic product with respect to the innovator formulation. Mean FFE24SS values at baseline and after repeated oral administrations of the generic and innovator formulations of orlistat were 0.88%, 40.55% and 40.54%, respectively. The ratio of least-squares means (LSM) of FFE24SS of the generic to the innovator formulation was 101.90%, with 90% confidence intervals of 97.94–106.01%. Orlistat was well tolerated by subjects in both periods of study and no serious adverse events were observed during the study. In conclusion, mean FFE24SS values were used as pharmacodynamic end-points to assess bioequivalence between two formulations of orlistat. Results from this study suggest that the test formulation of Orlistat capsule is bioequivalent to the reference marketed Alli™ when administered to healthy volunteers as a multiple dose under fed conditions.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82962193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statement of Retraction","authors":"Juan F. Rivelli, V. Santander, Sofía O. Peretti, N. E. Monesterolo, Ayelén D Nigra, Gabriela Previtali, M. R. Amaiden, C. Arce","doi":"10.3109/10601333.2013.809988","DOIUrl":"https://doi.org/10.3109/10601333.2013.809988","url":null,"abstract":"Activation of Aldose Reductase by Interaction With Tubulin and Involvement of This Mechanism in Diabetic Cataract Formation. Diabetes. 10 April 2014 [Epub ahead of print]. DOI: 10.2337/db13-1265 DOI: 10.2337/db13-1265 Juan F. Rivelli, Verónica S. Santander, Sofía O. Peretti, Noelia E. Monesterolo, Ayelen D. Nigra, Gabriela Previtali, Marina R. Amaiden, Carlos A. Arce, Emiliano Primo, Angela T. Lisa, Juan Pie, and César H. Casale The corresponding author has formally requested to retract the above-titled paper, which was published ahead of print on 10 April 2014. The following image manipulations were included in the original version of the work: 1) Fig. 1A and B: Molecular weight markers from one blot were paired up with lanes from another blot. 2) Fig. 1A: Lanes 5 and 7 (aldose reductase revealed with anti-tubulin and tubulin revealed with anti–aldose reductase) were exchanged in from another immunoblot analysis. 3) Fig. 1D: Immunoblot images do not represent the original image as a portion of a doublet of the tubulin band (at elution volume 4). The original source image was erased to show a single band. 4) Fig. 2A: The molecular weight marker lane has been extracted from a different blot, and the tubulin band was spliced in from another source and digitally altered with the eraser tool to provide a better picture.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81130634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steady state bioequivalence study of dipyridamole ER and acetyl salicylic acid 200 mg + 25  mg capsules in adult healthy male and female volunteers under fasting condition","authors":"S. Tippabhotla, Sandeep Yergude, C. Gadiko, S. Thota, Sohel Md. Khan, R. Battula, V. Vobalaboina","doi":"10.3109/10601333.2013.803113","DOIUrl":"https://doi.org/10.3109/10601333.2013.803113","url":null,"abstract":"Abstract The aim of the study was to evaluate the steady state pharmacokinetics and establish bioequivalence between the test (dipyridamole ER and acetyl salicylic acid 200 mg + 25 mg capsules of Dr. Reddy’s Laboratories Limited, India) against equal doses of reference (AGGRENOX® retard capsule of Boehringer Ingelheim Pharma GmbH & Co., KG 55216 Ingelheim am Rhein, Germany) formulations in 72 healthy adult male and female volunteers under fasting conditions. This was an open-label, block randomized, multiple dose, two-period, two-sequence, cross-over study separated by a washout period of 8 days. On day 5 of each period, post-dose blood samples were collected up to 12 h and analyzed for dipyridamole, salicylic acid and acetyl salicylic acid using a validated LC-MS/MS method. The 90% CI for dipyridamole (AUC(0–τ).ss, Cmax.ss and Cmin.ss) and for salicylic acid (AUC(0–τ).ss, Cmax.ss and %ptf) lie within the accepted bioequivalence range of 80.00–125.00%, thus permitting one to conclude for bioequivalence. In conclusion, both the formulations were well tolerated and the test product was bioequivalent to the reference product in terms of the rate and extent of absorption at steady state.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84419672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blinded independent central reviews: The FDA weighs in","authors":"R. Walovitch","doi":"10.3109/10601333.2013.812109","DOIUrl":"https://doi.org/10.3109/10601333.2013.812109","url":null,"abstract":"Abstract The FDA has recently issued a draft Guidance Standard for Clinical Trial Imaging Endpoints, which focuses on how to perform registration trials with imaging as an end-point or using imaging to determine patient eligibility. Leading up to the release of the guidance document, a major question was how the FDA viewed the value proposition of a blinded independent central review (BICR) of imaging data. The FDA states that a BICR is recommended in situations where clinical site image interpretation is variable and results of image measurements are important for eligibility determination, safety and/or efficacy end-points. This recommendation is based on the agency’s assertion that the centralized process can better provide verifiable and uniform reader training, as well as ongoing management of reader performance, ensuring that the process is accurate and that bias and variability are minimized. In addition to a review of the guidance document, this article will discuss a decision tree algorithm for determining when and what type of BICR should be performed, the relationship between bias (accuracy), variability and blinding paradigms, along with criteria for using BICRs to interpret non-imaging subjective clinical trial data.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73311663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single dose pharmacokinetics and bioequivalence of conjugated estrogens (0.625 mg × 2) tablets in healthy post-menopausal female subjects in fasting and fed studies","authors":"S. Tippabhotla, Mukesh Nakkawar, C. Gadiko, Madhava Rao Betha, Sohel Md. Khan, Sandeep Yergude, S. Thota, Raju Cheerla, R. Battula, V. Vobalaboina","doi":"10.3109/10601333.2013.771643","DOIUrl":"https://doi.org/10.3109/10601333.2013.771643","url":null,"abstract":"Abstract Conjugated estrogens are sulfate esters of naturally occurring estrogens. The pharmacokinetics of various estrogen formulations is complex and varying due to its endogenous availability. The present studies were designed to evaluate pharmacokinetic parameters and bioequivalence between two formulations of conjugated estrogens (0.625 mg tablets). Both the studies were designed as two-treatment, four-period, replicate cross-over single dose studies in 60 healthy post-menopausal female subjects under fasting and fed conditions, respectively. Since estrone is present endogenously, for baseline correction three pre-dose samples were obtained for total and unconjugated estrone. Plasma samples were analyzed by validated LC-MS/MS method and pharmacokinetic parameters were estimated for total and unconjugated forms of both estrone and equilin. The least square mean ratios and its 90% confidence interval for primary pharmacokinetic parameters Cmax, AUC0–t and AUC0–inf were found to be within bioequivalence limits of 80.00–125.00% for total and unconjugated forms of baseline corrected estrone and baseline un-corrected equilin. In conclusion, both test and reference products were well-tolerated and the test product was bioequivalent with the reference product in terms of the rate and extent of absorption in both fasting and fed studies.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81281278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advance Oracle Clinical Software tool used in clinical research from patient data collection to data base lock","authors":"Vasanth kumar Kunithala, Ahamed Kabeer, Sateesh Kumar Vemula","doi":"10.3109/10601333.2013.773441","DOIUrl":"https://doi.org/10.3109/10601333.2013.773441","url":null,"abstract":"Abstract This article is based on how the Oracle Clinical Software tool is used in clinical research. It is known that conducting research is a costly and time consuming process as it requires extra human resources, many software tools, and thorough knowledge of software in clinical research. This particular software helps in improving the trial performance and reduces the cost to the company. This article mainly describes the process of patient enrollment, data entry, data validation, E-data & SAE reconciliation, coding, discrepancy management, quality control process and data lock. Pharma Industries follow different methods for collecting, transferring, and storing patients data. Providing the knowledge of software tools to the persons who are involved in the trails will help them in simplifying their work. The objective is to provide complete knowledge of the Oracle Clinical Software tool by using proper guidelines of clinical trials. This also gives a complete idea of responsibilities and the functionality of data operation as well as tools analysis which would also help in tackling the risk profiles. All the above-mentioned applications would make one extract appropriate and consistent data of a patient, while submitting FDA.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86738691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics of two formulations of alendronate sodium/cholecalciferol (vitamin D3) tablets 70 mg/5600 IU: An open-label, randomized, single-dose, two-treatment, two-period, two-sequence, cross-over, bioequivalence study","authors":"S. Tippabhotla, S. Thota, Sohel Md. Khan, C. Gadiko, Sandeep Yergude, Raju Cheerla, Mukesh Nakkawar, Madhava Rao Betha, R. Battula, V. Vobalaboina","doi":"10.3109/10601333.2012.759586","DOIUrl":"https://doi.org/10.3109/10601333.2012.759586","url":null,"abstract":"Abstract A fixed dose combination of alendronate and cholecalciferol (vitamin D3) 70 mg/5600 IU tablets has been indicated for the treatment of osteoporosis. This study was aimed to assess bioequivalence between test and reference formulations of alendronate sodium/cholecalciferol (vitamin D3) tablets 70 mg/5600 IU in 110 healthy adult male volunteers under fasting conditions. This was an open label, randomized, single dose, two way cross-over study, separated by a washout period of 14 days. All possible efforts were made to stabilize the baseline endogenous levels of cholecalciferol. Blood samples were collected from 96 h pre-dose to 96 h post-dose and 0–24 h for cholecalciferol and alendronate, respectively. Quantification of alendronate and cholecalciferol was done using distinct validated LC-MS/MS methods. Two baseline adjusted methods, method-I (subtraction of the average concentration from each post-dose concentration) and method-II (subtraction of the individual AUC from post-dose AUC) were applied for deriving the AUC0–t parameter of cholecalciferol, among which bioequivalence was concluded based on data obtained using method-I. The 90% CI of Cmax and AUC0–t for alendronate and baseline adjusted cholecalciferol were within the regulatory acceptance limit of 80.00–125.00% and considered as bioequivalent.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85834910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Research and Regulatory Affairs invites you to submit your research","authors":"D. Hunter","doi":"10.3109/10601333.2012.759702","DOIUrl":"https://doi.org/10.3109/10601333.2012.759702","url":null,"abstract":"","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76081495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative bioavailability study of capecitabine tablets of 500 mg in metastatic breast cancer and colorectal cancer patients under fed condition","authors":"C. Gadiko, S. Tippabhotla, S. Thota, R. Battula, Mukesh Nakkawar, Sandeep Yergude, Sohel Md. Khan, Raju Cheerla, Madhava Rao Betha, V. Vobalaboina","doi":"10.3109/10601333.2012.752496","DOIUrl":"https://doi.org/10.3109/10601333.2012.752496","url":null,"abstract":"Capecitabine (oral prodrug of 5-fluorouracil) is the first-line treatment for the metastatic breast and colorectal cancer. The objective of the study was to determine the bioequivalence between the test product (capecitabine tablets 500 mg) of Dr. Reddy’s Laboratories Limited relative to that of reference product XELODA® (capecitabine) 500 mg tablets of Roche Registration Inc. in patients of metastatic breast or colorectal cancer stabilized with twice daily dosing of capecitabine monotherapy. This was an open-label, randomized, single dose, two-way cross-over bioequivalence study under fed conditions. The subjects received either of the treatments (test or reference) 30 min after consumption of a high fat, high calorie breakfast as a single morning dose of 2000 mg on two separate days (days 1 and 2) based on their body surface area. Blood samples were collected up to 10 h post-dose and analyzed for capecitabine using the validated liquid chromatographic mass spectrometric (LC-MS/MS) method. The least square mean ratio and 90% confidence intervals of Cmax, AUC0–t and AUC0–∞ were within the regulatory acceptance criteria of 80.00–125.00% and considered as bioequivalent.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77505087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steady-state pharmacokinetics and bioequivalence study of quetiapine fumarate film-coated tablets 300 mg in adult schizophrenic patients","authors":"Madhava Rao Betha, S. Tippabhotla, Sandeep Yergude, Sohel Md. Khan, Mukesh Nakkawar, C. Gadiko, S. Thota, Raju Cheerla, R. Battula, V. Vobalaboina","doi":"10.3109/10601333.2012.740485","DOIUrl":"https://doi.org/10.3109/10601333.2012.740485","url":null,"abstract":"Quetiapine is a dibenzothiazepine derivative approved for the treatment of schizophrenia and related psychoses. The objective of the present study was to design and evaluate the bioequivalence between quetiapine fumarate film-coated tablets of Dr. Reddy’s Laboratories Ltd., Hyderabad, India (test) and Seroquel® tablets (containing quetiapine) of AstraZeneca Pharmaceuticals LP Wilmington, DE, USA (reference). It was a two-way crossover steady-state multiple dose study in 54 adult schizophrenic patients under fasting conditions. Quetiapine was analyzed in plasma samples by using a validated liquid chromatographic mass spectrometry (LC-MS/MS) method. The pharmacokinetic parameters were estimated by noncompartmental method and mean (±SD) of Cmax,ss (ng/mL) for test and reference products were 1436.5 (±810.2) and 1413.1 (±905.5), respectively. The mean (±SD) of AUCτ,ss (ng·h/mL) for test and reference products were 6949.8 (±3879.8) and 6532.2 (±4279.4), respectively. The ratio of least square means and its 90% confidence interval for Cmax,ss and AUCτ,ss were found to be within bioequivalence limits 80.00–125.00%. In conclusion, test product was bioequivalent to the reference product in terms of both rate and extent of absorption under steady-state conditions.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75249875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}