A Retrospective Study to Evaluate Real-world Evidence of Azelnidipine in Indian Patients (REDEFINE Study).

INTRODUCTION: Azelnidipine, a selective calcium channel blocker, effectively lowers blood pressure (BP) and heart rate (HR) in hypertensive patients, as demonstrated in a retrospective real-world evidence (RWE) study in Indian patients. MATERIALS AND METHODS: This was a retrospective cohort study that included 882 patients aged 18 years or older who had been on azelnidipine treatment for the last 3 months for mild to moderate hypertension (HTN). A structured proforma was utilized to gather data from prescribing physicians to assess the efficacy of azelnidipine (8 and 16 mg) as monotherapy or in combination with other antihypertensive drugs. The primary endpoints of the study were to capture changes in systolic blood pressure (SBP) and diastolic BP (DBP) from baseline to the subsequent visits (4 and 12 weeks), while the secondary endpoints were to measure similar changes in the diabetic group and to estimate the proportion of patients achieving target BP of <130/80 mm Hg and <140/90 mm Hg, respectively. RESULTS: The overall mean reduction of systolic/diastolic BP from baseline to 12 weeks was 13.92/7.91 mm Hg (p-value < 0.0001). The mean reduction of systolic/diastolic BP from baseline to 12 weeks was 11.77/7.43 mm Hg (p-value < 0.0001) in newly diagnosed HTN patients, while in known cases of HTN, it was 16.50/8.48 mm Hg (p-value < 0.0001). In the diabetic group, the mean reduction was 15.35/8.69 mm Hg (p-value < 0.0001). Overall the study showed that in 44 (4.99%) and 408 (46.26%) patients, target BP of <130/80 mm Hg and <140/90 mm Hg, respectively was achieved. The mean change in HR from baseline was a reduction of 5.22 beats/minute. CONCLUSION: Azelnidipine can be an effective antihypertensive drug to treat mild to moderate HTN in Indian patients.

Correction: An Open-Label, Single-Arm, Multicenter, Observational Study Evaluating the Safety and Effectiveness of Akynzeo® in the Management of Chemotherapy-Induced Nausea and Vomiting in India.

[This corrects the article DOI: 10.7759/cureus.56447.].

An Open-Label, Single-Arm, Multicenter, Observational Study Evaluating the Safety and Effectiveness of Akynzeo® in the Management of Chemotherapy-Induced Nausea and Vomiting in India.

Background Chemotherapy-induced nausea and vomiting is a common and unpleasant treatment-related side effect reported by cancer patients receiving chemotherapy. Akynzeo® or NEPA (NEtupitant + PAlonosetron) is the first fixed combination of netupitant and palonosetron that targets both critical pathways involved in emesis while providing a convenient, single oral dose therapy. The current study aimed to assess the effectiveness and safety of NEPA in a real-world setting in India. Methodology This was an open-label, multicenter, prospective, single-arm study conducted at six different locations across India. The study included patients of either gender, aged ≥18 years, naive to chemotherapy, scheduled to receive highly or moderately emetogenic chemotherapy (HEC/MEC), and scheduled to receive oral NEPA, as determined by the investigator. Results A total of 360 people were screened and enrolled in the study. HEC was prescribed to 289 (81.64%) patients, while MEC was prescribed to 65 (18.36%) patients. Complete response was achieved in 94.92% of patients during the acute phase, 95.20% during the delayed phase, and 93.22% during the overall phase. During the overall phase, 92.73% and 95.38% of patients on the HEC and MEC regimens, respectively, achieved complete response. Adverse events were reported in 3.88% of patients. Conclusions Oral NEPA was found to be effective in the Indian real-world setting, eliciting a >90% complete response with HEC and MEC regimens across the acute, delayed, and overall phases.

Efficacy of Super-Bioavailable Itraconazole and Conventional Itraconazole at Different Dosing Regimens in Glabrous Tinea Infection - A Randomized Clinical Trial.

Introduction: Itraconazole follows non-linear pharmacokinetics and hence is recommended once daily, but in real-world practice, is commonly prescribed as twice daily. Hence, this study aimed to evaluate the efficacy and safety of super-bioavailable-itraconazole-130 mg (SB-130) and conventional-itraconazole-200 mg (CITZ-200) once daily compared with conventional-itraconazole-100 mg (CITZ-100) twice daily in glabrous tinea. Methods: A total of 261 eligible patients were enrolled in this prospective, randomized, clinical study from December-2021 to August-2022 at seven centers in India. Efficacy and safety assessments were done at week-3 and 6, with follow-up at week-10 for relapse. The primary objective was to assess the proportion of patients who achieved complete cure at week-6 following treatment in all itraconazole groups. The secondary outcomes were safety and clinical and mycological cure rates. Results: Of 261 patients, 240 were included in the analysis. At week-6, 140 patients were completely cured; thus, overall cure rate was 58.33%. Fifty-five patients (69%) in SB-130 while 47/77 (61%) and 38/83 (46%) patients were completely cured in CITZ-200 and CITZ-100 groups respectively (p<0.05; SB-130: CITZ-100, p=0.32; SB-130: CITZ-200, p=0.058; CITZ-200: CITZ-100). There was no statistical difference in the mycological cure rate and area clearance rate between any of the groups (p=0.14); however, a statistically significant difference was noted for OD dosing over BD dosing in achieving clinical cure rates (p<0.05). A total of 13/140 patients (9%) relapsed following complete cure, with no statistically significant difference between any of the groups (p=0.50). All treatments were safe and well-tolerated, with no discontinuation. Conclusion: In this clinical study, moderate efficacy with all doses of ITZ was reported but was better with OD dosing. Although there was no statistical difference between SB-130 and CITZ-200, SB-130 may be preferred over CITZ-200 owing to the advantage of SB over the conventional ITZ.

A Prospective, Randomized Open-Label Study for Assessment of Antihypertensive Effect of Telmisartan Versus Cilnidipine Using Ambulatory Blood Pressure Monitoring (START ABPM Study).

Background: The antihypertensive agent telmisartan is an angiotensin II receptor blocker with a terminal elimination half-life of 24 h and has a high lipophilicity, thereby enhancing its bioavailability. Another antihypertensive agent, cilnidipine is a calcium antagonist and has dual mode of action on the calcium channels. This study aimed at determining effect of these drugs on ambulatory blood pressure (BP) levels. Methods: A randomized, open-label, single-center study was conducted during 2021 - 2022 on newly diagnosed adult patients with stage-I hypertension, in a mega city of India. Forty eligible patients were randomized to telmisartan (40 mg) and cilnidipine (10 mg) groups, with once daily dose administered for 56 consecutive days. Ambulatory blood pressure monitoring (ABPM) (24 h) was performed pre- and post-treatment, and the ABPM-derived parameters were compared statistically. Results: Statistically significant mean reductions were observed in all BP endpoints in telmisartan group but only in 24-h systolic blood pressure (SBP), daytime and nighttime SBP, and manual SBP and diastolic blood pressure (DBP) in cilnidipine group. The mean change from baseline to day 56 between two treatment groups showed statistical significance in last 6-h SBP (P = 0.01) and DBP (P = 0.014), and morning SBP (P = 0.019) and DBP (P = 0.028). The percent nocturnal drop within and between groups was statistically nonsignificant. Also, the between group mean SBP and DBP smoothness index differed nonsignificantly. Conclusions: Telmisartan and cilnidipine once daily were effective and well tolerated in the treatment of newly diagnosed stage-I hypertension. Telmisartan provided sustained 24-h BP control and may offer advantages over cilnidipine in terms of BP reductions, particularly over the 18- to 24-h post-dose period or critical early morning hours.

Comparative Efficacy of Super Bioavailable Itraconazole Capsules 50 mg vs 65 mg Twice Daily in the Management of Glabrous Tinea.

Introduction: Owing to pharmacokinetic challenges of itraconazole, super-bioavailable itraconazole (SB) was developed and recently approved in strengths of 50mg and 65mg. But comparative study was lacking between these two strengths in glabrous tinea (dermatophytosis) management. Hence, this study was planned to compare the efficacy of both these strengths in dermatophytosis. Methods: One hundred eligible patients were enrolled in this prospective, randomized, clinical study during May-2022 to September-2022 at tertiary hospital in Ahmedabad in adults. Efficacy and safety assessments were done at week-3 and 6 with follow up at week-10 for relapse. Primary objective was to assess the proportion of patients achieving complete cure at week-6 following treatment in both the groups. Secondary outcomes compared safety, clinical and mycological cure rates. Results: Of the 100 patients enrolled, 98 patients (50 in SB-50mg and 48 in SB-65mg group) included in the final analysis. At week 6, 20 patients (40%) and 30 patients (62.5%) achieved complete cure (p < 0.05) in SB-50mg and SB-65mg groups, respectively. In completely cured patients, relapse was reported in 3 (15%) and 5 (17%) patients of SB-50mg and SB-65mg groups, respectively (p = 1). A significant difference was noted in clearance of symptoms and lesions in SB-65mg group (p < 0.05). Moreover, similar results were also obtained in sub-group analysis of recalcitrant dermatophytosis. Both the treatments were found to be safe and well tolerated with no discontinuation. Conclusion: Study result concluded the superiority of SB-65mg over SB-50mg in terms of cure rate and resolution of symptoms in dermatophytosis management.

The Indian REgistry on Current Patient PrOfiles and TReatment TrenDs in Hypertension (RECORD): Final Outcomes of the Real-world Observational Study.

Objectives: The Indian Registry on Current Patient Profiles and Treatment Trends in Hypertension (Record) evaluated the current trends and outcomes related to hypertension (HTN) management at 3, 6, 12, and 24 months in India. This study highlights and evaluates the outcomes and trends noted at 24 months. Materials and methods: The detailed study methodology is provided in the earlier publication (interim analysis at 12 months). Aspects such as changes in the quality of life (QOL), percentage of patients reaching target blood pressure (BP), treatment pattern among patients with comorbid conditions, and difference in treatment patterns between public and private healthcare settings, at 24 months, were evaluated in the current study. Results: The study population included 2,000 patients (55.7% males) with a mean age of 54.45 years. Telmisartan (43.7%) and amlodipine + telmisartan (16.4%) were the most prescribed monotherapy and combination therapy among patients with newly diagnosed HTN. A significant decrease in both systolic BP (SBP) and diastolic BP (DBP) was noted in the overall patient population at 24 months (p < 0.001). The mean change in SBP and DBP was slightly higher at 24 months compared to 12 months. This was more evident among patients on combination therapy. A significant improvement in QOL was noted at 24 months. Conclusion: Treatment strategies in HTN management are changing and are associated with effective HTN control and improvements in QOL. However, there is a further need for improved awareness regarding the optimal usage of combination therapy for better management of uncontrolled HTN. How to cite this article: Rajadhyaksha GC, Reddy H, Singh AK, et al. The Indian REgistry on Current Patient PrOfiles and TReatment TrenDs in Hypertension (RECORD): Final Outcomes of the Real-World Observational Study. J Assoc Physicians India 2023;71(11):43-49.

Safety and immunogenicity of a single dose, live-attenuated 'tetravalent dengue vaccine' in healthy Indian adults; a randomized, double-blind, placebo controlled phase I/II trial.

BACKGROUND: Dengue fever is the most prevalent mosquito-borne viral disease in the world, with 390 million dengue infections occurring every year. There is an unmet medical need to develop a safe, effective and affordable dengue vaccine against all four Dengue serotype viruses-DENV1, DENV-2, DENV-3 and DENV-4. Panacea Biotec Ltd (PBL) has developed a cell culture-derived, live-attenuated, lyophilized Tetravalent Dengue Vaccine (TDV). Here, in phase I/II study we assessed the safety and immunogenicity of single dose 'Dengue Tetravalent Vaccine' in healthy Indian adults. METHODS: In the study, 100 healthy adult volunteers aged 18-60 years were enrolled. The participants were allocated to TDV and placebo groups in 3:1 ratio, i.e. 75 participants to TDV group and 25 participants to the placebo group. Enrolled participants were administered a single dose of 0.5 ml of the test vaccine / placebo by subcutaneous route. Primary outcome for safety included all solicited AEs up to 21 days, unsolicited AEs up to 28 days and all AEs/serious adverse events (SAEs) till day 90 post-vaccination. For immunogenicity assessment the primary outcome was seroconversion & seropositivity rate by PRNT50 to all four serotype till 90 days. RESULTS: Overall, 100 subjects were vaccinated out of which 8 subjects (5 subjects in vaccine group and 3 subjects in placebo group) dropped out from the study. The most commonly reported solicited local AE was pain and most common solicited systemic AE was headache and fever. No SAE was reported during the study. There was no statistically significant difference between TDV and placebo groups in terms of AEs. Of the 92 subjects who completed all scheduled visits in the study, 59 (81.9%) achieved seroconversion for DENV-1, 56 (77.8%) for DENV-2; 59 (81.9%) for DENV-3 and 57 (79.2%) for DENV-4 in TDV group. The seroconversion rate in the TDV group was statistically significant (p < 0.001) compared to placebo.Clinical trial registration: CTRI/2017/02/007923.

Bioequivalence of two tacrolimus 1-mg formulations under fasting conditions in healthy subjects: A randomized, two-period crossover trial
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OBJECTIVE: The present study compared the pharmacokinetics of two (1 mg) tacrolimus formulations (test (generic from Panacea) and reference (innovator from Astellas)) after a single-dose administration as per the European Medicine Agency (EMA) guidelines to grant marketing authorization. MATERIALS AND METHODS: This study was a randomized, open-label, balanced, two-treatment, two-period, two-sequences, single-dose, truncated-area, crossover design with a washout period of 19 days between the phases. Healthy subjects aged 18 - 45 years (both inclusive) were included. Eligible subjects received a single oral dose of 5 × 1-mg capsule of tacrolimus either test or reference formulation. Blood samples were collected until 72.00 hours postdose, and peak concentration (Cmax) and area under the curve (AUC0-72) were evaluated in whole blood using validated LC-MS/MS. Safety was also assessed in each period. RESULTS: Of 56 subjects enrolled, 52 completed both study periods. The arithmetic mean (SD) Cmax for the reference and test formulations was 40.62 (11.30) and 46.20 (10.73) ng/mL, and AUC0-72 was 348.34 (156.41) and 361.04 (158.71) ng×h/mL, respectively. The geometric least square mean ratio (90% confidence interval (CI)) was 115.07% (90% CI: 109.81, 120.59) for Cmax and 103.78 (90% CI: 97.40, 110.58) for AUC0-72, which fell within the acceptance range as per EMA guidelines for narrow therapeutic index drugs (Cmax: 80.00 - 125.00%; AUC: 90.00 - 111.11%). No serious adverse event was observed. CONCLUSION: The generic tacrolimus was bioequivalent to the reference formulation, was well tolerated, and provides a well-acceptable alternative to the reference drug. Switching treatment to generic tacrolimus medication may reduce the cost and economic burden of treating transplanted patients.

Theoretical design for generation of slow light in a two-dimensional magneto optical trap using electromagnetically induced transparency.

In this paper, we propose a novel technique for slow light experiments using electromagnetically induced transparency using a two-dimensional magneto optical trap (2D-MOT). A compact 2D-MOT design efficient for quantum memory applications with adjustable optical depth (OD) is proposed. We estimated the OD for our 2D-MOT setup and found that light group velocities as low as 1.4 m/s can be attained. Our design for 2D-MOT allows precise control and optimization of the OD such that high storage efficiencies could also be achieved. With our design, it is possible to obtain a delay bandwidth product of 163, which is very high in comparison to previously obtained values.