Efficacy and safety of 0.05% micellar nano-particulate (MNP) cyclosporine ophthalmic emulsion in the treatment of moderate-to-severe keratoconjunctivitis sicca: a 12-week, multicenter, randomized, active-controlled trial.

BACKGROUND: Keratoconjunctivitis sicca or dry eye disease (DED) is a multifactorial disorder underpinned by a complex inflammatory cycle. Introduction of topical cyclosporine has been a significant advance in the management of DED. In recent years advancements in formulation technology have led to development of micellar nano-particulate (MNP) cyclosporine formulations that promise better penetration into ocular target tissues and potential for reduced ocular surface irritation. METHODS: We compared two dosing regimes of a proprietary MNP cyclosporine emulsion with the widely marketed topical cyclosporine formulation Restasis™ in a multicenter parallel-group randomised trial in patients with DED. Patients were randomised to one of 3 treatment groups with 90 patients eligible for the per protocol analysis: 30 in the higher dose test arm A; 32 in the lower dose test arm B; and 28 in the Restasis™ control arm C. All scored efficacy endpoints were tested for significance by comparing the mean change in scores from baseline in the test groups with that in the control group at 12 weeks, using the Student's t test. Wilcoxon's rank sum test was used to test individual symptom scores and clinician's global evaluation of treatment grades. RESULTS: Corneal fluorescein staining score, the primary efficacy endpoint, decreased by 6.8 ± 4.0, 5.7 ± 3.9, and 4.6 ± 3.6 points in the 3 groups respectively, indicating superior efficacy in test arm A in comparison to control arm C (p = 0.0026). Schirmer's tear test, conjunctival lissamine staining score, ocular surface disease index, and individual dry eye symptom scores also favoured higher dose MNP cyclosporine over Restasis™. The study failed to differentiate the treatment arms in terms of clinician's global evaluation of treatment, use of tear substitutes, best corrected visual acuity or safety and toleration. CONCLUSION: The results indicate that the dose of 1 drop of a 0.05% w/v ophthalmic emulsion of MNP cyclosporine administered topically twice daily yields better outcomes at 12 weeks than the lower dose tested in the study, and is more efficacious than an equivalent dose of Restasis™, the active control used in the study. TRIAL REGISTRATION: This trial was registered in the Clinical Trials Registry of India on 29/03/2019, and was assigned registration number CTRI/2019/03/018319.

A review of clinical trials registered in India from 2008 to 2022 to describe the first-in-human trials.

Aim: This analysis was conducted to review the number, and describe the characteristics of first-in-human (FIH) Phase 1 clinical trials registered in India from 2008 to 2022. Materials and Methods: The data were extracted from the Clinical Trials Registry - India database for all FIH Phase 1 clinical trials registered between 2008 and 2022. Early-phase trials that were not FIH trials (e.g., pharmacokinetic studies and drug-drug interaction studies) were excluded from the study. Results: A total of 1891 trials were retrieved and 220 were included in the analysis. Most of the investigational products were drugs (55%) followed by vaccines (38.2%). The most common therapeutic class of drugs was cancer chemotherapy (19.8%), followed by antimicrobial chemotherapy and endocrinology (18.2% each). The most common vaccine was the influenza vaccine (21.4%), followed by the measles-mumps-rubella vaccine (15.5%). The pharmaceutical industry was the predominant sponsor for most (91%) of the Phase 1 trials. Of the top five sites where most of the Phase 1 trials were conducted, three were private nonacademic centers (cumulatively 31%) and two were tertiary care medical colleges (cumulatively 9%). Conclusion: Phase 1 clinical trials seem to be conducted in India predominantly with industry sponsorship. There is a need to have an alternate ecosystem to take forward molecules that do not receive adequate attention from the industry and molecules that are of national health priority other than areas such as chemotherapy, antimicrobials, and endocrinology. The Indian Council of Medical Research is setting up Phase 1 clinical trial capacity for molecules that predominantly may arise from nonindustry channels.

Pharmacovigilance Symposium ISCR Annual Conference Jan 5, 2013: Safety aspects of hard endpoint or outcome trials.

The articles describes some highlights of the Pharmacovigilance Symposium held during Annual conference.

Compensation conundrum.

Pressured by questions tabled in parliament that point to a lack of adequate enforcement of regulations, the DCG(I) has abruptly initiated action to ensure payment of compensation for trial-related injuries. While it is astounding that non-compliance to the existing regulations could have gone unnoticed by quality assurance staff as well as by the ethics committees and the regulator, for over six years, sudden enforcement of the regulation has thrown up issues and challenges that are difficult to resolve in the absence of an adequately debated and thought-through guidance. In implementing regulations for suo moto compensation, India is seeking to establish a practice not previously tested elsewhere in the world. There is no doubt that industry must support the idea of putting patients first, but procedural considerations in fixing causality and determining the quantum of compensation promise to raise questions of morality, ethics, and jurisprudence that will not be easy to answer.

Clinical trials and contract research organizations in India.

Economics and demography are driving drug development to the developing world. India needs this opportunity to build research skills required to combat its enormous disease burden. A variety of global and local contract research organizations (CROs) that specialize in the execution of research to develop health care products operate in India today. CROs assure quality and compliance to regulations while coordinating with tertiary providers such as a site management organization and the central laboratory. Back room operations to manage, analyze, and report data form a bulk of the employment generated by clinical research, absorbing programmers, data managers, biostatisticians,and medical writers. Despite rapid growth and strong potential, India remains a minor contributor to global pharmaceutical research because of policy stagnation, regulatory gaps, and misinformed controversies in the media.

Microdosing: concept, application and relevance.

The use of microdose pharmacokinetic studies as an essential tool in drug development is still to catch on. While this approach promises potential cost savings and a quantum leap in efficiencies of the drug development process, major hurdles still need to be overcome before the technique becomes commonplace and part of routine practice. Clear regulations in Europe and the USA have had an enabling effect. The lack of enabling provisions for microdosing studies in Indian regulation, despite low risk and manifest relevance for the local drug development industry, is inconsistent with the country's aspirations to be among the leaders in pharmaceutical research.