Search

Background Widespread antibiotic resistance has sparked interest in the identification of nonantibiotic strategies, particularly probiotics for the prevention of recurrent urinary tract infections (UTIs). We evaluated the effectiveness of prophylactic probiotic supplementation through oral and intravaginal routes in the prevention of recurrent UTIs. Methods This double-blind, placebo-controlled study enrolled 174 premenopausal women with a history of recurrent UTIs and randomized them to 1 of the 4 treatment groups: placebo (G1, oral placebo + vaginal placebo), oral probiotic (G2, oral lactic acid bacteria and bifidobacteria + vaginal placebo), vaginal probiotic (G3, oral placebo + vaginal lactobacilli), and probiotic combination (oral lactic acid bacteria and bifidobacteria + vaginal lactobacilli), for 4 months. Participants were followed up for symptomatic UTIs for 1 year. The primary end points were the number of symptomatic UTIs at 4 months, the proportion of participants with at least 1 symptomatic UTI, and the time to the first symptomatic UTI. Results The incidence of UTI at 4 months in G1, G2, G3, and G4 was 70.4%, 61.3%, 40.9%, and 31.8%, respectively. The mean number of symptomatic UTI recurrences at 4 months was significantly lower (P <.05) in G3 (1.06) and G4 (1.07) compared with G1 (2.1) and G2 (1.63). Further, the time to first symptomatic UTI (days) was significantly longer (P <.05) in G3 (123.8) and G4 (141.8) compared with G1 (69.3) and G2 (71.9). Probiotic supplementations were well tolerated with no serious adverse events. Conclusions Prophylactic supplementation with either vaginal probiotics or in combination with oral probiotics demonstrated effectiveness in preventing recurrent symptomatic UTI episodes. Clinical Trials Registration Registered at Clinical Trials Registry India (CTRI): CTRI/2014/02/004425 (https://ctri.nic.in). [ABSTRACT FROM AUTHOR]

Background: Obesity is one of the critical public health problems in our society. It leads to various health conditions, such as type 2 diabetes mellitus, cardiovascular disease, hypertension, dyslipidaemia, and non-alcoholic fatty liver disease. With the rising incidence of obesity, there is a growing demand for new therapies which can effectively manage body weight and improve health. Current evidence: Currently under development, multi-receptor agonist drugs may offer a promising solution to meet this unmet medical need. Retatrutide is a novel triple receptor agonist peptide that targets the glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon-like peptide-1 receptor (GLP-1R). This novel drug has the potential to treat metabolic abnormalities associated with obesity as well as diseases resulting from it due to its distinct mechanism of action. The Phase III trial of this pipeline drug for treating type 2 diabetes mellitus, non-alcoholic fatty liver disease, and obesity started on August 28, 2023. The results of a Phase II clinical trial have demonstrated significant weight reduction in overweight and obese adults. Specifically, the trial reported an average weight loss of 17.5% and 24.4% at 24 and 48 weeks, respectively. Conclusions: These findings hold promise for the development of effective weight loss interventions in this population group. There is a need for more phase III studies to provide sufficient clinical evidence for the effectiveness of retatrutide, as current evidence is limited to phase II studies and has yet to prove its worth in a larger population. Here, we aimed to provide an overview of retatrutide's safety and effectiveness in treating obesity. [ABSTRACT FROM AUTHOR]

Through the New Drugs and Clinical Trials Rules, 2019 (2019 Rules), India has developed the rules governing post-trial access (PTA) to new drugs or investigational new drugs. However, inconsistencies and interpretational challenges exist in the application of the 2019 Rules and the Indian Council of Medical Research Guidelines 2017. This conflation poses a real harm to the trial participants, specifically the ones with limited access to healthcare facilities. Since drug laws in India do not expressly deal with other forms of access like the 'Compassionate Use' or 'Expanded Access' mechanism, demarcating the scope and describing the strategies for PTA are the need of the hour. We propose possible strategies to address inadequacies in the regulatory regime and establish 'win–win' situations among all stakeholders. We further argue that India is well positioned to provide leadership by developing detailed PTA provisions and may set a potential path for the other clinical trial host countries. [ABSTRACT FROM AUTHOR]

The article focuses on the reasons for the prevalence of Multidrug Resistant Tuberculosis (MDR TB) and the impact of COVID-19 on Tuberculosis. Topics include the spread of MDR TB due to irregular treatment and poor adherence to medications, the importance of early diagnosis using molecular tests, and the challenges faced in managing TB during the COVID-19 pandemic.

Background: Under the New Drugs and Clinical Trials Rules -2019 that came into force on 14th September 2019, all Ethics Committees (ECs) reviewing biomedical and health research should register with the authority designated by the Central Government of India. Study Objective: We investigated the status of registration of ECs in the Department of Health Research (DHR) to date. Materials and Methods: The data collection was started on 1 April, 2021 and was last updated on 10 April, 2022. The ECs registered with DHR were extracted from NAITIK online portal. The ECs were segregated according to the state and Union territories, medical colleges, dental colleges, and hospital and research institutes. Results: Total of 836 registered ECs were uploaded on the DHR website to date. Out of which, 822 (98.32%) were Institutional and 14 (1.67%) were independent. Among total ECs, 518 (61.96%) were in hospitals and research institutes, 231 (27.63%) in medical colleges, and 73 (8.73%) in dental colleges. 76 (9.09%) got the final certificate after completion of a provisional period of two years. Among 606 medical colleges and 316 dental colleges, 38.11% and 23.10% of colleges had registered ECs respectively. Maharashtra has the highest number with 129 (15.43%) registered ECs whereas Gujarat is number one (53.33%) in terms of percent registered ECs in medical colleges of particular states. Conclusions: Timely registration of ECs should be encouraged by the concerned stakeholders and try to make a robust mechanism for bringing transparency, uniformity, and accountability to the ECs across the states. [ABSTRACT FROM AUTHOR]

Introduction: The Investigational New Drug (IND) committee advises the Drug Controller General of India on matters pertaining to clinical trials (CTs) of IND for clinical development. An audit of the minutes of this committee's meetings would shed light on the drug discovery in India. Methods: Minutes of the IND committee meetings available in the public domain (2-year period) were evaluated. The applications which were postponed were excluded from the study. Outcome measures were therapeutic areas of IND, purpose of the applications, status of registration with the CT Registry of India (CTRI), and the innovator country. Results: The minutes of N = 7 meetings were available in the public domain for the period January 2017–December 2018 with N = 45 agenda items. One agenda item was excluded, and n = 44 agenda items were finally analyzed. The total number of therapeutic agents discussed was N = 29, of which n = 7/29 and n = 6/29 belonged to infectious diseases (ID) and oncology, respectively. The total number of purposes of these applications was N = 46, of which n = 35/46 (76%) were to seek permission to conduct a CT, and n = 31/35 (88.6%) were found registered with CTRI as on April 01, 2019. Of the N = 46 purposes, n = 33/46 (71.7%) were approved. Of the n = 29 INDs discussed, n = 19/29 (65.52%) were of the Indian origin. Conclusions: Although a majority (65%) of INDs discussed in the meetings were of the Indian origin, the drug discovery was not in line to tackle the top ten causes of years of life lost prematurely (barring ID). [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) presenting with pulmonary and extra-pulmonary manifestations. The first case was reported in Wuhan, China in December 2019 and it has rapidly progressed to the form of a pandemic. The presentation is mild in about 80 percent of the cases but the disease can also progress to a severe form of respiratory illness leading to acute respiratory distress syndrome (ARDS) and sometimes multi-organ failure, especially in people with other co-morbidities. Pregnant women also appear to be at a greater risk of acquiring a severe infection due to physiological changes during pregnancy. Many drugs with in vitro activity against the virus or an immunomodulatory effect have been considered for repurposing or have been tried as off-label drugs. The safety data regarding the use of newly approved or off-label or investigational drugs in pregnant women is limited and this poses a great challenge for clinicians. Therefore, it is important to know the utility and safety of the medications to avoid untoward adverse effects on pregnant women and fetuses. In this review, we aim to provide an overview of the approved, off-label, unlicensed, new and some promising pharmacological options for their use in the treatment of COVID-19 and the safety profile in pregnancy in an Indian scenario. [ABSTRACT FROM AUTHOR]

Cocaine addiction continues to impose major burdens on affected individuals and broader society but is highly resistant to medical treatment or psychotherapy. This study was undertaken with the goal of Food and Drug Administration (FDA) permission for a first-in-human clinical trial of a gene therapy for treatment-seeking cocaine users to become and remain abstinent. The approach was based on intravenous administration of AAV8-hCocH, an adeno-associated viral vector encoding a modified plasma enzyme that metabolizes cocaine into harmless by-products. To assess systemic safety, we conducted "Good Laboratory Practice" (GLP) studies in cocaine-experienced and cocaine-naive mice at doses of 5E12 and 5E13 vector genomes/kg. Results showed total lack of viral vector-related adverse effects in all tests performed. Instead, mice given one injection of AAV8-hCocH and regular daily injections of cocaine had far less tissue pathology than cocaine-injected mice with no vector treatment. Biodistribution analysis showed the vector located almost exclusively in the liver. These results indicate that a liver-directed AAV8-hCocH gene transfer at reasonable dosage is safe, well tolerated, and effective. Thus, gene transfer therapy emerges as a radically new approach to treat compulsive cocaine abuse. In fact, based on these positive findings, the FDA recently accepted our latest request for investigational new drug application (IND 18579). [ABSTRACT FROM AUTHOR]

Background: To fulfil the objective of fast-tracking the accessibility of new drugs and promoting clinical research in India, the Union Ministry of Health and Family Welfare, India has notified the "New Drugs and Clinical trials Rules, 2019" on 25th March 2019. The prime objective of the new rule is to initiate unambiguous, foreseeable and effective regulations for the clinical trials in India. Drugs Controller General of India (DCGI) affirmed that the new rules would apply to all new drugs, investigational new drugs, bioequivalence and bioavailability study (BA/BE) and ethics committees. The new rules would replace part XA and schedule Y of drugs; however, the existing rules (Drugs and Cosmetics Act, 1940; Drug and Cosmetics Rules, 1945) and licenses, orders or directions will remain valid. Purpose: This brief review aims at presenting the key highlights of the "New Drugs and Clinical Trials Rules, 2019" of India. Methods: Literature review in existing and new clinical trials rules in India was conducted by referring the articles published in the indexed journals and official websites and compared. Conclusion: The clinical trials approval timeline has moved down to 30 days for the domestic trials and 90 days for the approval of global clinical trials. This faster approval timelines in the newly amended rules have enabled approval of more number of clinical trials and as a result, India may again turn out to be the preferred centre for conducting the trials. [ABSTRACT FROM AUTHOR]

Background. Pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. In highly regulated markets, there are currently no approved biosimilars of pegfilgrastim. Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2) was a confirmatory efficacy and safety study designed to compare proposed biosimilar LA-EP2006 with reference pegfilgrastim (Neulasta, Amgen) in early-stage breast cancer patients receiving adjuvant or neoadjuvant myelosuppressive chemotherapy. Methods. A total of 308 patients were randomized to LA-EP2006 or reference pegfilgrastim. Each patient received TAC (intravenous docetaxel 75 mg/m², doxorubicin 50 mg/m², and cyclophosphamide 500 mg/m²) on day 1 of each cycle, for sixor more cycles. Pegfilgrastim (LA-EP2006 or reference) was given subcutaneously (6 mg in 0.6 mL) on day 2 of each cycle. The primary endpoint was duration of severe neutropenia (DSN) during cycle 1 (number of consecutive days with an absolute neutrophil count <0.5 3 109/L), with equivalence confirmed if 90% and 95% confidence intervals (CIs) were within a 1-day margin. Results. Baseline characteristics were well balanced. DSN was equivalent between groups at mean ± SD 1.36 ± 1.13 (LA-EP2006, n = 155) and 1.19 ± 0.98 (reference, n = 153) in cycle 1. With a treatment difference (reference minus LA-EP2006) of -0.16 days (90% Cl -0.36 to 0.04; 95% CI -0.40 to 0.08), LA-EP2006 was equivalent to reference pegfilgrastim. Secondary efficacy parameters were similar between groups during cycle 1 and across cycles. Safety profiles were also similar between groups. No neutralizing antibodies against pegfilgrastim, filgrastim, or polyethylene glycol were detected. Conclusion. LA-EP2006 and reference pegfilgrastim were therapeutically equivalent and comparable regarding efficacy and safety in the prevention of neutropenia in patients with early-stage breast cancer receiving TAC. [ABSTRACT FROM AUTHOR]

The $90 billion Indian pharma industry has been unable to develop a new drug for the US market despite spending millions in research, even though Indian generics constitutes 40 per cent of US generic drug imports. Ranbaxy and Zydus have been able to launch indigenously developed new drugs in domestic market, but none of the Indian pharmaceutical companies have launched a new drug approved by USFDA. Until a few years ago (2005–2012), Para IV filing opportunities in the US had engaged the Indian firms quiet significantly. Today, that option is no longer is attractive due to limited Para IV opportunities being targeted by numerous firms. Of late, super generics have emerged as the industry’s hope for the future. They have caught the attention of branded players as some categories enjoy a measure of patent protection (3–5 years) in US under Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act (FFDCA). This article is aimed at studying the concept of incremental research in pharmaceutical industry, development cycle and regulatory pathway for super generics, profitability estimates and possibilities in future for Indian firms. [ABSTRACT FROM AUTHOR]

To streamline and give impetus to drug discovery and development in the country, the Government of India in early part of the previous decade set up Investigational New Drugs (INDs) Committee under the chairmanship of Director General, ICMR, for the evaluation of clinical trials for INDs. When an applicant raises a CT application in the regulatory system, there is no prediction as to which pathway the application would take - i.e., whether it would be considered under the IND committee or the SEC committee. [Extracted from the article]

Newer management options are needed for leprosy control even at present, as it is predicted that new cases of leprosy will continue to appear for many more years in future. This article detail newer methods of clinical grading of peripheral nerve involvement (thickening, tenderness and nerve pain which are subjective in nature) and the advances made in the use of Ultrasonography and Colour Doppler as an objective imaging tool for nerves in leprosy. It also briefly discusses the newer drugs and alternative regimens as therapeutic management options which hold promise for leprosy in future. [ABSTRACT FROM AUTHOR]

The article offers information on regulations related to clinical trials in India. The Drug Technical Advisory Board (DTAB) has proposed to delete the clause which requires compensation for failure of investigational drug. The Indian Ministry of Health and Family Welfare has asked for changes in the Drugs and Cosmetic Act of 1940 to include audio-video (AV) recording of consent.

The article discusses the issue of Road traffic accident (RTA) and drivers. The lack of awareness of the effects of anti‑histamines on safe driving is a real issue for truck drivers and a challenge for prevention of accidents. It presents a study conducted in Navi Mumbai, India from June 15 to 20, 2011. Alcohol can potentiate the sedative effects of anti‑histamines. A physician should be sensitized about sedating potential of older anti‑histamines.