Pharmacokinetics, Pharmacodynamics, Efficacy and Safety of a Romiplostim Biosimilar in Chronic Refractory Immune Thrombocytopenic Purpura (ITP) Patients.

Unlabelled: Romiplostim (Nplate®, Amgen Inc.) is an orphan drug approved for the treatment of chronic refractory immune thrombolytic purpura (ITP) in adult and pediatric patients. Limited availability of pharmacokinetic (PK) data and large inter- and intra-subject variability in PK and platelet response is a challenge in the clinical development of a romiplostim biosimilar.

A review of use errors reported in human factor validation studies of biological combination products.

Drug-device combination products should be safe and effective for intended uses by intended users under intended use environment during human factor (HF) studies. All known use errors and use-related problems should be considered during design of device and use-related risk analysis. Availability of such information in a compiled manner is scarce.

Denosumab biosimilar in postmenopausal osteoporotic women: A randomized, assessor-blind, active-controlled clinical trial.

Objective: The study assessed the efficacy, safety, pharmacokinetic (PK), and immunogenicity profiles of denosumab-biosimilar and denosumab-reference in postmenopausal osteoporotic women from India.

Materials And Methods: In this randomized, assessor-blind, active-control, multicenter trial, 114 patients were randomly allocated to receive denosumab-biosimilar (n = 58) or denosumab-reference (n = 56) at a subcutaneous dose of 60 mg every 6 months, for a year. Vitamin D and oral calcium were given daily.

Safety and efficacy of Razumab™ (world's first biosimilar ranibizumab) in wet age-related macular degeneration: a post-marketing, prospective ASSET study.

Background: Razumab™ (world's first biosimilar ranibizumab) is approved for several macular disorders including wet age-related macular degeneration (AMD). We evaluated the safety and efficacy of biosimilar ranibizumab in wet AMD.

Methods: This prospective, multicentre, rAnibizumab bioSimilar Safety Efficacy postmarkeTing (ASSET) study enrolled patients aged ≥ 50 years with wet AMD having best-corrected visual acuity (BCVA) between 20/40 and 20/320.

Regulatory Approval Scenario of Biosimilars in Pediatric Patients in the United States and European Union.

Regulatory agencies of the USA and European Union (EU) have introduced multiple guidelines in the last decade to standardize and accelerate biosimilar development. As a result, a large number of biosimilars are being approved in the USA and EU. In the present review, we identified the biosimilars and their corresponding reference biologics approved for pediatrics in the USA and EU, and then assessed their approval details.

Single-Dose Pharmacokinetics, Pharmacodynamics and Immunogenicity, and Multiple-Dose Immunogenicity of INTP5 (Pegfilgrastim Biosimilar) Versus Reference Pegfilgrastim in Healthy Subjects.

Unlabelled: BACKGROUND AND OBJECTIVE: INTP5 has been developed as a pegfilgrastim biosimilar. Single-dose, crossover study compared the pharmacokinetics and pharmacodynamics (PK/PD) of INTP5 (pegfilgrastim biosimilar) with reference pegfilgrastim (Neulasta, pegfilgrastim-ref) and a multiple-dose, parallel-group study compared the immunogenicity of INTP5 with pegfilgrastim-ref in healthy subjects as part of a complete clinical development plan.

Methods: In the PK/PD study, subjects received a single subcutaneous 6 mg dose of INTP5 and pegfilgrastim-ref (N = 142) separated by a 6-week washout period.

A randomized, double-blind, parallel-group, single‑dose, pharmacokinetic bioequivalence study of INTP24 and bevacizumab in healthy adult men.

Purpose: To demonstrate pharmacokinetic (PK) equivalence and to compare safety of INTP24 (bevacizumab biosimilar) with that of US-bevacizumab and EU-bevacizumab in healthy male subjects.

Methods: In this randomized, parallel-group, double-blind study, male subjects were randomized (1:1:1) to receive a single 1 mg/kg intravenous infusion of either INTP24, US-bevacizumab, or EU-bevacizumab. The primary endpoint was area under serum concentration (AUC) from time zero to infinity (AUC).

Bevacizumab for eye diseases - Legal, regulatory, and ethical overview.

Vascular endothelial growth factor (VEGF) inhibitors, ranibizumab, aflibercept, and pegaptanib are approved treatments for certain eye diseases that occurs especially in the elderly. These drugs are mostly inaccessible due to their high cost. Bevacizumab is a VEGF inhibitor, approved for cancer treatment.

Insights into human factor studies conducted for US FDA-approved biological combination products.

: With increasing use of biological products and devices, importance of human factor (HF) studies is increasing. The HF study ensures safe and effective use of the device by intended users, for intended uses, under intended use environments.: This review compiles information of HF studies conducted for biological combination products (biological products plus device) approved by US FDA's Center for Drug Evaluation and Research between 21 June 2011 and 31 December 2018.

Pharmacokinetics and Pharmacodynamics of Insulin Tregopil in Relation to Premeal Dosing Time, Between Meal Interval, and Meal Composition in Patients With Type 2 Diabetes Mellitus.

We evaluated the pharmacokinetics and pharmacodynamics of oral insulin tregopil in relation to premeal dosing time, between-meal interval, and meal composition type in type 2 diabetes mellitus patients in a randomized, placebo-controlled, crossover study consisting of 3 sequential cohorts. In Cohort 1, insulin tregopil administered 10 to 20 minutes before a meal resulted in optimal postmeal exposure and demonstrated better postprandial glucose-lowering effect (glucose area under concentration-time curve [AUC]) compared to the 30-minute group. In Cohort 2, insulin tregopil pharmacokinetic exposure (plasma AUC) showed a progressive increase through 4, 5, and 6 hours of between-meal interval.

An update on the animal studies conducted for biosimilar approvals - Regulatory requirement vs actual scenario.

Nonclinical animal studies are considered as an integral part of biosimilar development program to demonstrate similarity and safety. We have compiled, reviewed and summarized animal studies conducted for European Medicines Agency (EMA) and United States Food and Drug Administration (US FDA) submission from 2006 till December 2018. The commonest animal studies conducted included repeat-dose toxicity study along with toxicokinetic, local tolerance and immunogenicity assessments, while the least common included primary pharmacodynamic, pharmacokinetic, safety pharmacology and single-dose toxicity studies.

Impact of Insulin Tregopil and Its Permeation Enhancer on Pharmacokinetics of Metformin in Healthy Volunteers: Randomized, Open-Label, Placebo-Controlled, Crossover Study.

Oral insulin tregopil (IN-105; a new drug under development) may be coadministered with oral antidiabetic drugs, such as metformin in patients with type 2 diabetes mellitus for optimal glycemic control. IN-105 has sodium caprate excipient, a permeation enhancer, for enhancing absorption in the stomach and increasing bioavailability via an oral route. Sodium caprate may increase bioavailability of metformin by a similar mechanism.

FOXP1 negatively regulates tumor infiltrating lymphocyte migration in human breast cancer.

Background: FOXP1, a transcriptional regulator of lymphocyte development, is abnormally expressed in some human tumors. This study investigated FOXP1-mediated regulation of tumor infiltrating lymphocytes (TIL) in untreated primary breast cancer (BC).

Methods: FOXP1 expression was analyzed in tissues from primary untreated breast tumors, BC cell lines and the METABRIC gene expression BC dataset.

Pharmacokinetic and pharmacodynamic bioequivalence study of a pegfilgrastim biosimilar INTP5 in healthy subjects.

Purpose: This study compared pharmacokinetics, pharmacodynamics, safety and immunogenicity profiles of INTP5 (a potential pegfilgrastim biosimilar) with that of Neulasta.

Methods: In this randomised, assessor-blind, crossover study, 344 healthy subjects received single subcutaneous dose of both INTP5 and Neulasta at 3 mg/0.3 ml (n = 172) or 6 mg/0.

CD73 Promotes Resistance to HER2/ErbB2 Antibody Therapy.

Expression of the ectonucleotidase CD73 by tumor cells, stromal cells, and immune cells is associated in cancer with immune suppression. In this study, we investigated the role of CD73 on the activity of the anti-HER2/ErbB2 monoclonal antibody (mAb) trastuzumab. In a prospective, randomized phase III clinical trial evaluating the activity of trastuzumab, high levels of CD73 gene expression were associated significantly with poor clinical outcome.

Biology of breast cancer during pregnancy using genomic profiling.

Breast cancer during pregnancy is rare and is associated with relatively poor prognosis. No information is available on its biological features at the genomic level. Using a dataset of 54 pregnant and 113 non-pregnant breast cancer patients, we evaluated the pattern of hot spot somatic mutations and did transcriptomic profiling using Sequenom and Affymetrix respectively.

Treatment failure with disease-modifying antirheumatic drugs in rheumatoid arthritis patients.

Introduction: Rheumatoid arthritis (RA) patients taking disease-modifying antirheumatic drugs (DMARDs) may experience treatment failure due to adverse effects or a lack of efficacy/resistance. The purpose of this study was to evaluate the prescription patterns, the incidence and reasons for failure, and the time to treatment failure of DMARDs in RA patients.

Methods: The medical records of patients visiting the Rheumatology Clinic were scrutinised retrospectively in order to extract the relevant data, including demographics, clinical and laboratory investigations and drug usage, for analysis.

Causes of DMARD withdrawal following ADR within 6 months of initiation among Indian rheumatoid arthritis patients.

The present study was conducted in Indian rheumatoid arthritis (RA) patients prescribed disease-modifying anti-rheumatic drugs (DMARDs) to determine the incidence and type of adverse drug reactions (ADRs) leading to their withdrawal in the initial 6 months of therapy. This was considered important as pharmacogenetic variations in the pattern of RA in different populations and genetic differences in efficacy and safety to drugs demand separate studies to be conducted in different populations. Hospital records were used to identify 1,000 consecutive patients with RA fulfilling the American College of Rheumatology criteria and having at least 6-month follow-up.

Changing chronobiology of cardiovascular outcome following prophylaxis.

Cardiovascular events like angina, myocardial infarction and stroke have shown an increasing occurrence in the morning hours. We did this pilot nested case control study to see for any change in the time pattern of occurrence of cardiovascular events among patients on prophylaxis. A pilot study was done and the demographic characters, history of cardiovascular diseases, time of occurrence of cardiovascular event, history of drug intake and compliance were noted.

Antiepileptic TDM pattern at a tertiary care hospital in India.

Therapeutic drug monitoring, a comparatively new investigational procedure in clinical pharmacology, is considered very beneficial to epilepsy patients though it increase the health care cost. Aim of this study was to determine the pattern of use of antiepileptic drug level monitoring over the last 7 years in our tertiary care centre and to critically comment on its utility. Retrospective data audit of archived data from 1998 to 2004 and age, sex, estimated levels of phenytoin, carbamazepine and phenobarbitone by HPLC were noted down, tabulated and compared.

Effect of potassium channel modulators on toxicity of Cleistanthus collinus.

The study was conducted to determine the effects of boiled extract of Cleistanthus collinus on rats by observing ECG changes and electrolyte levels in serum and urine. Influence of minoxidil and glibenclamide on Cleistanthus collinus induced toxicity was determined. ED50 for arrhythmia, changes in contractility and heart rate were recorded using the isolated frog heart.