No abstract

ClinicalTrials.gov identifier NCT00362050.

The available data support the evaluation of a drug combination in a larger population as a fixed-dose combination. Clinical Trials Registration. CTRI/2007/091/000031.

With the ever increasing demand for screening millions of prospective "novel coronavirus" or COVID-19 cases, and due to the emergence of high false negatives in the commonly used PCR tests, the necessity for probing an alternative simple screening mechanism of COVID-19 using radiological images (like chest X-Rays) assumes importance. In this scenario, machine learning (ML) and deep learning (DL) offer fast, automated, effective strategies to detect abnormalities and extract key features of the altered lung parenchyma, which may be related to specific signatures of the COVID-19 virus. However, the available COVID-19 datasets are inadequate to train deep neural networks. Therefore, we propose a new concept called domain extension transfer learning (DETL). We employ DETL, with pre-trained deep convolutional neural network, on a related large chest X-Ray dataset that is tuned for classifying between four classes viz. normal, other disease, pneumonia and Covid − 19. A 5fold cross validation is performed to estimate the feasibility of using chest X-Rays to diagnose COVID-19. The initial results show promise, with the possibility of replication on bigger and more diverse data sets. The overall accuracy was measured as 95.3% ± 0.02. In order to get an idea about the COVID-19 detection transparency, we employed the concept of Gradient Class Activation Map (Grad-CAM) for detecting the regions where the model paid more attention during the classification. This was found to strongly correlate with clinical findings, as validated by experts.

Arterolane (RBx 11160) maleate is a novel, rapidly acting synthetic trioxolane antimalarial compound being developed by Ranbaxy Research Laboratories (Haryana, India). It is presently under phase III in combination with piperaquine phosphate. The present work reports the relationship between pharmacokinetic (PK) parameter (AUC(0-8h) on day 0/day 6) and indices of pharmacodynamic (PD) response (50% parasite clearance [PC(50)], 90% parasite clearance [PC(90)], parasite clearance time [PCT], recrudescence) from a phase II, double-blind, multicenter, randomized, parallel-group, dose-ranging trial. Patients with acute uncomplicated P. falciparum malaria were randomized to 1 of 3 arterolane maleate (50, 100, and 200 mg) doses for 7 consecutive days. Plasma concentration data were available from 78, 76, and 75 patients receiving a 50-, 100-, and 200-mg dose, respectively. Based on PD modeling, its limitations and assumptions, minimum 150-mg dose arterolane maleate was recommended to optimize the probability of maximum therapeutic benefits for an adult. Doses higher than 100 mg are unlikely to reduce the probability of recrudescence. This study re-stresses the need of combining short and long-acting drugs to prevent resistance development and minimize recrudescence.

Piperaquine phosphate is an orally active bisquinolone antimalarial drug that has been used for the past 3 decades. The authors report the safety, tolerability, and pharmacokinetics of piperaquine from a classical controlled phase I study. It was a double-blind, randomized, parallel-group, placebo-controlled, and single- and multiple-dose study. During the rising single-dose study, single ascending oral doses of 500, 750, 1000, 1250, and 1500 mg of piperaquine phosphate were administered, whereas in rising multiple-dose study, once-daily ascending oral doses of 500, 750, 1000, and 1500 mg were administered for 3 consecutive days. Pharmacokinetic analysis for both the rising single- and multiple-dose studies was done using the noncompartmental approach. The mean apparent terminal half-life ranged from 11 to 23 days. Increase in exposure was less than dose proportional and linear. Piperaquine concentrations were measurable up to 60 days postdose. Multiple peaks were observed in the plasma piperaquine concentration-time profiles and exhibited 3- to 7-fold accumulation following multiple dosing. Piperaquine was well tolerated following single and multiple doses.

Arterolane (RBx11160, OZ277) maleate is a rapidly acting synthetic trioxolane anti-malarial. This randomized, placebo controlled study was a phase I study to evaluate the clinical safety and tolerability as well as pharmacokinetics (PKs) of arterolane maleate including food effect. Eight single rising oral doses of arterolane (25, 50, 100, 150, 200, 300, 400, 600 mg), food effect under fed and fasting conditions at 100 mg dose and four multiple oral dose regimens (25, 50, 100, 200 mg) were administered once daily for 7 days in 64 healthy young males (Caucasian). A randomized, placebo-controlled study was also conducted in healthy elderly males and females (Caucasian) to investigate PKs, safety and tolerability of single oral dose (100 mg) of arterolane. All doses were well tolerated after oral administration. The initial peak of arterolane was apparent at 2-3 hours post-dose followed by a secondary peak at approximately 5 hours post-dose. Thereafter, plasma arterolane concentration declined with a geometric mean t1/2 of approximately 2-4 hours. The PKs of arterolane appeared to be time-invariant after repeated once-daily dosing. The incidence of adverse events was similar for placebo and active treatments. Arterolane had similar PKs and tolerability in elderly and younger subjects and between elderly males and females.

India. CTRI/2009/091/000101.