Abstract

Background

Trelagliptin and vildagliptin are oral dipeptidyl peptidase-4 (DPP-4) inhibitors used in the treatment of type 2 diabetes mellitus. The administration of vildagliptin is twice daily, whereas trelagliptin provides the convenience of once-weekly dosing, which may enhance patient adherence. A phase 3 clinical trial was conducted to assess the non-inferiority of trelagliptin compared to vildagliptin.

Methods

This multicenter, randomized, open-label, parallel-group, active-controlled non-inferiority clinical trial was conducted at 10 geographically distinct sites across India. A total of 240 treatment-naive patients with type 2 diabetes mellitus were randomized in a 1:1 ratio to receive either trelagliptin (100 mg once weekly) or vildagliptin (50 mg twice daily) for 16 weeks. The primary endpoint was non-inferiority of trelagliptin to vildagliptin in reducing glycated hemoglobin (HbA1c) levels from baseline to week 16. Secondary efficacy measures included changes in fasting and postprandial blood glucose, fasting insulin, glucagon, C-peptide, and glucagon-like peptide-1 (GLP-1) levels. Safety was assessed based on the incidence of adverse events.

Results

At week 16, the mean HbA1c levels were 7.18 ± 1.47% and 7.21 ± 1.49% in trelagliptin and vildagliptin groups, respectively (Δ -0.89% vs. Δ -1.00%, p < 0.0001). The difference between groups was 0.11% (95% CI: -0.28 to 0.50; p = 0.5899), showing non-inferiority of trelagliptin. A total of 48.57% of patients in the trelagliptin group and 47.57% in the vildagliptin group achieved the target HbA1c level of <7% (p = 0.8850). No statistically significant differences were observed between the groups for glycemic parameters, including fasting blood glucose (Δ 1.11; 95% CI: -16.79 to 19.02; p = 0.9025), 2-hr postprandial glucose (Δ 3.33; 95% CI: -30.55 to 23.88; p = 0.8093), fasting serum insulin (Δ 5.22; 95% CI: -15.01 to 25.45; p = 0.6113), fasting glucagon (Δ 0.72; 95% CI: -96.34 to 94.90; p = 0.9882), C-peptide (Δ 0.36; 95% CI: -0.31 to 1.03; p = 0.2912), and GLP-1 levels (Δ -0.02; 95% CI: -0.06 to 0.02; p = 0.3995). All reported adverse events were mild in nature and resolved without any lasting effects. Adverse events occurred in 6.67% (8/120) of patients in the trelagliptin group and 9.17% (11/120) in the vildagliptin group.

Conclusions

Trelagliptin showed a significant reduction in HbA1c, fasting, and postprandial glucose levels, indicating effective glycemic control in patients with type 2 diabetes mellitus. The study drug exhibited a favorable safety profile, with no major adverse events reported. Overall, trelagliptin proved to be both efficacious and well-tolerated, demonstrating non-inferiority to vildagliptin.

Background: Catechins and epicatechins are monomers of naturally occurring proanthocyanidins, which have been reported with free radical scavenging, antioxidant, antiinfl ammatory, antiallergic, and vasodilatory properties. Plant parts rich in proanthocyanidins have been used for years in treatment of various ano-rectal diseases. This study compares the effi cacy of two herbal preparations, Dafl on® 500 mg and Roidosanal® , in ameliorating the signs and symptoms associated with hemorrhoids.

Objective: To evaluate the safety and to compare the effi cacy of a herbal preparation, Roidosanal® versus Dafl on® 500 mg, on signs and symptoms of hemorrhoidal disease.

Materials and Methods: In this pilot, active controlled, open-labeled multicentre study, 73 patients with proctoscopy proven hemorrhoids (Grade I to III) were randomly assigned to receive either Roidosanal® (Gr R; n = 37) or Dafl on® 500 mg (Gr D; n = 36), for 15 days, at three centers in India. Assessment of hemorrhoidal symptoms was carried out in all patients at different time points. Intent-to-treat analysis was performed for both primary and secondary endpoints.

Results: Baseline characteristics were comparable between the two groups. Both products were found to be equally effective in improving the ano-rectal conditions in Grade I and Grade II hemorrhoids; however, Roidosanal® demonstrated better effi cacy in patients with Grade III hemorrhoids. Hemorrhoids associated symptoms like bleeding, pain, etc., improved in both groups, although intergroup comparisons were comparable. Conclusion: Both Roidosanal® and Dafl on® 500 mg were equally effective in resolving signs and symptoms of hemorrhoids. Roidosanal® can be tried as a safe and effective treatment option for treatment of hemorrhoids. Further randomized, double-blind and large multicentre studies are recommended

Aim and background: To assess the efficacy and safety of Ibutilide infusion for cardioversion of atrial fibrillation (AF) or flutter (AFL) to sinus rhythm. Materials and methods: This open-label, multicenter phase IV study was conducted at six sites across India. The study enrolled 120 patients (108 with AF, 12 with AFL), each receiving up to two, 10-minute intravenous doses of 1.0 mg Ibutilide. The primary endpoints were the proportion of patients achieving cardioversion and the mean time taken to achieve cardioversion. Secondary endpoints included the proportion of patients maintaining sinus rhythm at 24 hours and the incidence of adverse events.

Results: The cardioversion rate at 4 hours post-Ibutilide infusion among 120 patients was 65.83% (n = 79), with an average conversion time of 35.12 ± 36.71 minutes. At 24 hours, 85 patients (70.8%) had successful cardioversion, with a mean time of 107.24 minutes. The majority of patients (71.76%) had achieved cardioversion within 30 minutes. Of the 85 patients who achieved successful conversion, 82 (68.3%) maintained sinus rhythm at 24 hours. A total of 66 patients (55%) achieved cardioversion with the first bolus whereas 19 (15.8%) needed a second bolus. Atrial fibrillation patients had a higher conversion rate (75%) compared to AFL patients (33%). A total of 10 adverse events were recorded in eight patients (6.67%), including nausea, headache, palpitations, and bradycardia. Three severe cardiac events, one case of ventricular tachycardia, and two of tachycardia necessitated discontinuation of Ibutilide. No fatalities or serious adverse events (SAE) were reported.

Conclusion: Ibutilide was found to be effective and well-tolerated for rapid restoration of sinus rhythm in patients with AF or AFL.

Clinical Trial Registry of India: CTRI/2018/01/011248.

Keywords: Atrial fibrillation, Atrial flutter, Cardioversion, Ibutilide

Preterm birth (PTB) continues to be a leading cause of neonatal mortality and long-term complications globally, reinforcing the need for effective and safe tocolytic treatments. Atosiban, an oxytocin receptor antagonist, has emerged as a pivotal intervention for managing spontaneous preterm labour (sPTL) due to its targeted mechanism and favourable safety profile. This is especially critical in regions like India, where there is a significant therapeutic gap in the availability of effective, safe, and cost-efficient tocolytic agents.

Dosing regimens for Atosiban include a full course (48 hours), a brief course (14 hours), and a single bolus dose. The brief and bolus regimens are particularly advantageous in settings that prioritize shorter hospital stays or outpatient management, offering a more convenient and cost-effective approach. These regimens also provide the flexibility of repeat treatments if necessary, enhancing patient care adaptability. Extensive clinical studies have validated Atosiban's efficacy and safety across its various dosing regimens.

Although Atosiban has a high initial cost compared to its alternatives, such as β2-agonists and calcium channel blockers, its superior safety profile and targeted action result in fewer maternal and fetal side effects, thereby reducing overall healthcare costs. The ability to manage sPTL with shorter regimens alleviates the strain on healthcare resources and minimizes the need for intensive neonatal care, with significant cost savings.

Overall, Atosiban represents a valuable therapeutic option for managing preterm labour. Its proven efficacy, safety, and cost-effectiveness make it a preferred choice for tocolysis, particularly in high-risk pregnancies like those with diabetes or cardiac issues.

Abstract

Background:

The global burden of respiratory diseases in India has drawn attention due to their high prevalence, socioeconomic impact, and lack of effective prevention measures.

Objective:

This study aimed to evaluate the safety and efficacy of a fixed-dose combination (FDC) of Paracetamol, Phenylephrine and Chlorpheniramine tablet in adults with common cold.

Methods: This study was conducted at four different locations across India and involved the participation of 200 individuals exhibiting common cold symptoms of recent onset. They were administered Maxtra®P tablets [FDC of Paracetamol 500mg, Phenylephrine Hydrochloride 10mg, and Chlorpheniramine Maleate 4mg] every 4 to 6 hours for a duration of 5 days. The primary endpoint focused on assessing the safety and tolerability of the investigational drug. This evaluation relied on the identification of adverse events (AEs) experienced by the patients and global assessment reported by both the Investigator and the patients. Secondary endpoint, aimed at analyzing efficacy, the proportion of patients achieving complete resolution and a reduction in the severity of symptoms.

Results:

Adverse events such as nausea and dizziness, mild in severity, were experienced by two patients. However, they were resolved without any sequelae and were found not related to the study drug. Patients and investigators rated the treatment as “good to excellent” in alleviating symptoms associated with common cold in 92.5% (n = 185) and 99.5% (n = 199) of adults respectively, suggesting a positive response. A comprehensive assessment of 11 symptoms of common cold was conducted to evaluate the efficacy of the study drug. Complete resolution from the symptoms was achieved in 75% of patients and a statistically significant (p< 0.0001) reduction was observed in individual symptom severity score on day 5 as compared to baseline. A notable reduction in TSS (Total Symptom Score) was demonstrated where mean TSS at baseline was 16.05 which was reduced to 0.41 at day 5 (mean diff: 15.64, CI: 14.61 to 16.67, p< 0.0001).

Conclusion: Paracetamol, Phenylephrine Hydrochloride and Chlorpheniramine Maleate FDC was well tolerated and efficacious in the symptomatic treatment of common cold in adults.

Abstract:

Introduction: The common cold affects children frequently, with 7-10 episodes annually, imposing significant economic and social burdens. Early management to reduce symptom severity and duration is crucial.

Objective: To evaluate the safety and efficacy of a fixed dose combination (FDC) syrup containing paracetamol, phenylephrine, and chlorpheniramine, for treating common cold symptoms in children aged 6- 18 years.

Methods: The study was conducted in India from March 2021 to December 2022, included 200 children aged 6 to <18 years with cold symptoms lasting 6-72 hours. They received paracetamol 250 mg, phenylephrine hydrochloride 5 mg, and chlorpheniramine maleate 2 mg per 5mL syrup for 5 days. For safety evaluation, the incidence of adverse events and the tolerability of study treatment were assessed, while improvement in common cold symptoms and complete resolution were assessed to evaluate the efficacy of the study treatment.

Results: One patient reported mild drowsiness unrelated to the study drugs. Treatment was well-tolerated, with "good to excellent" responses reported by 94% (parents) and 95% (investigators). Symptom severity significantly decreased by day 5 (p<0.001), with total symptom scores reducing from 9.12 to 0.13 (mean diff: 8.99, 95%CI: 7.86-10.12; p<0.001). 92% of patients showed complete symptom resolution by study end, with no symptom worsening.

Conclusion: The FDC of paracetamol, phenylephrine, and chlorpheniramine syrup effectively managed common cold symptoms in children aged 6 years and older, demonstrating good tolerability.

ABSTRACT

Background: Common cold often accompanied by mild fever and systemic symptoms in children, poses a significant social burden. Scientific evidence suggests that the pathogenesis of colds involves the activation of multiple inflammatory pathways, rendering single-molecule treatment ineffective against the symptoms. This active post-marketing surveillance study evaluated the safety and efficacy of a fixed-dose combination containing paracetamol, phenylephrine hydrochloride, and chlorpheniramine malate in treating common cold in children aged 2 to 5 years.

Methods: In this clinical study, 200 children with common cold symptoms were enrolled. Maxtra^® P oral drops, a fixed-dose combination containing paracetamol (125 mg), phenylephrine hydrochloride (2.5 mg), and chlorpheniramine maleate (1 mg) per ml drops, were administered as 1 ml every 4 to 6 hours for 5 days. Safety was assessed using the global tolerability assessment based on responses from parents and investigators. Efficacy was evaluated based on symptom severity scores categorised as absent, mild, moderate, severe, or very severe.

Results: Complete remission from common cold symptoms was achieved in 82% (164 patients) of 200 patients. Statistically significant reductions (p<0.001) in symptom severity scores were observed for all common cold symptoms from day 1 to day 5. No adverse events were observed. Maxtra^® P oral drops were regarded as good to excellent for treating common cold symptoms by 92.5% of parents and 97.5% of investigators.

Conclusions: The observations of study indicate that Maxtra^® P oral drops are efficacious and well- tolerated for treating common cold in children aged 2 to 5 years.

Abstract

Background: The common cold ranks as the most frequently encountered respiratory illness in pediatric medical practice. Although not considered serious, the common cold is widespread and can be debilitating, leading to school absenteeism, disturbed sleep, redduced food intake, and interference with daily routines. It impacts not only a child’s general well-being but also family life as it may require parents to stay home to care for sick children. The main goals of common cold management are the reduction of symptom duration and severity. Effective treatments for common cold include over-the-counter analgesics, nasal saline irrigation, decongestants, and with or without antihistamines.

Aims: To evaluate the safety and symptomatic efficacy of a fixed dose combination of Paracetamol 125mg, Phenylephrine 5mg, and Chlorpheniramine maleate 1mg per 5 ml (Maxtra®P) syrup in Indian children with common cold.

Method: This active post-marketing surveillance study was carried out from February 2021 to November 2022. A total number of 200 children with common cold were prescribed Maxtra®P syrup for patients of age 6 to 18 years for 5 days. Safety assessment was done by analysing adverse events during the trial and assessment of treatment response. Efficacy assessment was based on a reduction in the severity of symptoms and the number of patients achieving complete remission at the end of the study.

Results: Out of 200 children, 93% achieved complete relief from common cold symptoms on day 5. At the end of the study, symptoms such as sneezing, headache, hoarseness, wheezing, difficulty in breathing, and malaise completely disappeared in all children. A statistically significant reduction (p < 0.0001) in symptom score was observed for all the symptoms from baseline to day 5. Maxtra®P syrup was well-tolerated and the results suggest no new safety concerns. Mild adverse events such as drowsiness and dizziness were reported in two children. Patients and investigators rated Maxtra®P syrup treatment as ‘good’ and ‘excellent’ in providing symptomatic relief in 94% and 96.5% of children respectively, suggesting a positive global response to treatment.

Conclusion: Maxtra®P syrup was found to be well tolerated and efficacious in the symptomatic relief of the common cold in the Indian pediatric population.