Patara Pharma (United States)

Topical use of antibacterial drugs as part of complex therapy for purulent-inflammatory infections of the skin and oropharynx can not only eliminate the symptoms but also influence the cause of the disease. Dioxidine® is a broad-spectrum antibacterial drug, active against both gram-positive and gram-negative bacteria. The aim of this study was to investigate the bioavailability, pharmacokinetic parameters, and safety profile of Dioxidine®, solution for topical and external use, 0.25 mg/ml, in cutaneous and topical application. Another dosage form of Dioxidine® — a solution for infusion and external use, 5 mg/ml — was used as a comparison drug. The study consisted of 4 stages reflecting different routes of drug administration: rinsing the oropharynx (path A), a single irrigation of the oropharynx using a spray nozzle (path B), back skin irrigation (path C), and intravenous administration (path D — for the reference drug). The results of the study made it possible to determine the absolute dose-normalized bioavailability of the study drug in the indicated routes of administration, as well as to evaluate its safety profile.

The cyclin‐dependent kinase (CDK)4/6‐cyclin D1‐Rb‐p16/ink4a pathway is responsible for regulating cell progression past the G1 restriction point during the cell cycle. The development of a majority of human tumors is associated with dysregulation of this pathway, resulting in increased cancer cell proliferation. Both CDK4 and CDK6, well‐validated cancer drug targets, function primarily as catalytic enzymes that mediate the phosphorylation of retinoblastoma protein (Rb). Here, we determined that SPH3643 is a novel potent antiproliferative agent that inhibits CDK4/6 kinase activity. In biochemical assays, SPH3643 showed more potent inhibition of both CDK4 and CDK6 than did 2 published CDK4/6 inhibitors, LY2835219 and palbociclib, and had better selectivity than LY2835219. Further in vitro study revealed that SPH3643 blocked Cdk/Rb signaling by inhibiting the phosphorylation of RbSer780 and arrested the MCF‐7 cancer cells at G0/G1 phase, resulting in marked inhibition of the proliferation of Rb‐positive cancer cell lines. In vivo SPH3643 treatment in mice bearing xenograft tumor models of breast cancer, colon cancer, acute myelocytic leukemia, and glioblastoma resulted in significant decreases in tumor growth. SPH3643 was able to particularly strongly inhibit glioblastoma (U87‐MG) cell growth in the brains of orthotopic carcinoma xenograft mice due to its high degree of intracerebral penetration and significant persistence in this setting. Together these results revealed that SPH3643 is a potent, orally active small‐molecule inhibitor of CDK4/6 with robust anticancer efficacy and a high degree of blood‐brain barrier permeability.

Patient adherence to the protocol in clinical trials is a critical factor in determining the outcome of the trial. An investigational eFlow nebulizer was used with an eTrack controller featuring adherence-monitoring capability (PARI Pharma, Germany) to deliver drug to the lungs via inhalation and to objectively monitor adherence. The inhalation data were available via the PARItrack web portal and allowed evaluation and graphical visualization of each patient's adherence. The clinical trial involved 10 patients who self-administered drug in their homes twice a day for 6 weeks. The eTrack controller automatically transferred data of each nebulization via a Bluetooth connection to a 2netHub (Qualcomm) and via GSM to a server. The data could be accessed through the PARItrack web portal. The clinical trial nurses, investigators and CRO could remotely monitor adherence and an alert system was established for information on missed inhalations. This allowed individual adherence issues to be addressed immediately and corrective actions to be implemented to ensure ongoing adherence. This setup resulted in a high adherence rate over the duration of the clinical trial. The overall mean adherence rate was 96 %. Seven out of ten patients had an adherence rate of 100 %, two had 95 %, and one had 64 %. This compares with a reported adherence rate of 78 % in the first 4 weeks of another clinical trial using a monitoring nebulizer without remote data access and intervention [Fuchs et al. ECFC 2011]. The high adherence rates achieved in this study demonstrate the utility of remote monitoring and immediate intervention to achieve good adherence in a clinical trial.

BackgroundThe prevalence of type 2 diabetes mellitus (T2DM) and obesity is increasing in Korea. Clinical studies in patients with T2DM have shown that combining the glucagon-like peptide-1 receptor agonist exenatide twice daily with basal insulin is an effective glucose-lowering strategy. However, these studies were predominantly conducted in non-Asian populations.MethodsWe conducted a subgroup analysis of data from a multinational, 30-week, randomized, open-label trial to compare the effects of exenatide twice daily (n=10) or three times daily mealtime insulin lispro (n=13) among Korean patients with T2DM inadequately controlled (glycosylated hemoglobin [HbA1c] >7.0%) on metformin plus optimized insulin glargine.ResultsExenatide twice daily and insulin lispro both reduced HbA1c (mean −1.5% and −1.0%, respectively; P<0.01 vs. baseline). Fasting glucose and weight numerically decreased with exenatide twice daily (−0.7 mmol/L and −0.7 kg, respectively) and numerically increased with insulin lispro (0.9 mmol/L and 1.0 kg, respectively). Minor hypoglycemia occurred in four patients receiving exenatide twice daily and three patients receiving insulin lispro. Gastrointestinal adverse events were the most common with exenatide twice daily treatment.ConclusionThis analysis found treatment with exenatide twice daily improved glycemic control without weight gain in Korean patients with T2DM unable to achieve glycemic control on metformin plus basal insulin.