Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials.

BACKGROUND: Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD). METHODS: TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300). FINDINGS: Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]). INTERPRETATION: Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD. FUNDING: F Hoffmann-La Roche.

Efficacy, durability, and safety of faricimab in patients from Asian countries with neovascular age-related macular degeneration: 1-Year subgroup analysis of the TENAYA and LUCERNE trials.

PURPOSE: To evaluate 1-year efficacy, durability, and safety of faricimab among patients from Asian countries in the TENAYA/LUCERNE trials of neovascular age-related macular degeneration (nAMD). METHODS: Treatment-naïve patients with nAMD were randomly assigned (1:1) to faricimab 6.0 mg up to every 16 weeks (Q16W), based on disease activity at weeks 20 and 24, or aflibercept 2.0 mg Q8W. The primary endpoint was change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48. RESULTS: In the pooled TENAYA/LUCERNE trials, there were 120 (9.0%) and 1209 (91.0%) patients in the Asian (faricimab n = 61; aflibercept n = 59) and non-Asian country (faricimab n = 604; aflibercept n = 605) subgroups, respectively. In the Asian country subgroup, mean BCVA change from baseline at the primary endpoint visits was 7.1 (95% CI, 4.3-9.8) letters with faricimab and 7.2 (4.4-10.0) letters with aflibercept. In non-Asian country patients, mean vision gains were 6.1 (5.2-7.1) and 5.7 (4.8-6.7) letters with faricimab and aflibercept, respectively. At week 48, 59.6% of Asian country patients in the faricimab group achieved Q16W dosing (vs. 43.9% non-Asian) and 91.2% achieved ≥ Q12W dosing (vs. 77.5% non-Asian). Central subfield thickness reductions were similar between the subgroups, with meaningful and similar reductions from baseline observed at the primary endpoint visits and over time. Faricimab was well tolerated in both subgroups, with an acceptable safety profile. CONCLUSION: Consistent with the global TENAYA/LUCERNE findings, faricimab up to Q16W showed sustained visual and anatomical benefits in patients with nAMD from Asian and non-Asian countries. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03823287 (TENAYA); NCT03823300 (LUCERNE). Date of registration: January 30, 2019.

Exploring novel and fast stability or sameness evaluation tool for different categories of injectable formulations.

The establishment of drug product stability and sameness is the heart of generic formulation development. For regulatory filing, various instrumental methods are used on a case basis to establish the generic and innovator product sameness in multiple aspects. Here in the present study, we explored the applicability of the Time-correlated single photon counting (TCS-PC) technique as a fast, reliable, and nondestructive method for establishing the sameness of three different categories of injectable formulations, namely, Amphotericin B liposome for injection, enoxaparin injection, and iron sucrose injection. All three category formulations were evaluated in their native and artificially induced post degradation state to identify the discrimination power of the used instrumental techniques. The degradation of materials were confirmed by high performance liquid chromatography (HPLC). Based on the product category, pre and post-degradation samples were evaluated by selective instrumental methods like differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), fluorescence spectroscopy, particle size analysis by dynamic light scattering (DLS), small angle X-ray scattering (SAXS), Raman spectroscopy, inductively coupled plasma optical-emission spectrometry (ICP-OES) and circular dichroism study. All pre and post-degradation samples were further analyzed by TCS-PC. We observed that, TCS-PC can identify the differences between the initial and post degradation samples in very less time with promising discrimination power across the different injectable formulation types. Thus TCS-PC can be used as a fast and promising stability or sameness evaluation tool for different injectable drug products.

Factors affecting sterilization operation among couples of a rural area in Ahmedabad: a record-based study.

INTRODUCTION: Various socio demographic factors play role in sterilization operation. MATERIALS AND METHODS: A record-based study was conducted in Jetalpur, rural area of Ahmedabad District. Records of all sterilization operation done between April 2010 to March 2011 were studied. RESULTS: A total of 180 sterilization operations were performed, of which 179 (99.4%) were female sterilization and one (0.6%) was vasectomy. The mean age of females was 28.27 years and that of their husbands was 31.72 years. Total 45% of females in the study population were illiterate, whereas 17% of their husbands were illiterate and their average family size was 2.8 members. Majority of females underwent sterilization operation when the age of last living child was between 1-5 years. In 67% cases, female health worker was the motivator. Only two couples had no living male child, whereas all other couples had at least one male child in the family. There was no significant relationship between the education of the mother and the age of the last living child, but education of mother was significantly related to the total number of living children in the family. Education of the father was significantly related with the age of last living child and the total number of living children in the family. CONCLUSION: The study reveals that education of both parents is an important driving factor in deciding the size of family. Majority of couple decide for permanent sterilization after having at least one male child. Thus, there is a strong preference for at least one male child in the family.

Comparative Study Of Efficacy Of Palonosetron With Dexamethasone Versus Granisetron With Dexamethosone In Laproscopic Abdominal Surgeries For Control Of Post Operative Nausea And Vomiting.

Background & Aim: This study was carried out to demonstrate the efficacy and compare a dose of Granisetron with Dexamethasone and Palonosetron with Dexamethasone for prophylaxis against postoperative nausea and vomiting. Aim is to study the effectiveness of palonosetron and granisetron with aims of evaluating the efficacy of palonosetron and granisetron with dexamethasone in prevention of postoperative nausea and vomiting and to study associated adverse effects. The study was carried out in Civil Hospital, Ahmedabad with prior permission of ethical committee of the hospital. Methodology: This study was designed to evaluate the efficacy and compare a dose of study drugs in 60 patients of either sex and age ranging from 18 to 60 years and physical status ASA risk I or II undergoing general anaesthesia for various laparoscopic surgical procedures. Patients were divided into 2 groups(n=30), assigned to receive granisetron 1mg plus dexamethasone 8mg i.v and palonosetron 0.075mg plus dexamethasone 8mg i.v. A standard general anaesthesia technique and post operative analgesia were used throughout our study. The groups were compared with regards to the incidence of complete response, mean PONV score, mean nausea VDS scores and requirement of rescue anti emetics drug at various intervals (0-6,6-24,24-72hrs). Differences in continuous variables (age and duration of anaesthesia) across two dosage groups were compared using analysis of variance (ANOVA) test which is a parametric statistical test. Differences in categorical variables (gender, presence of complete response, use of rescue anti-emetics) across two dosage groups were compared using chi square test. Differences in ordinal variables (PONV scores and 4-point verbal descriptive nausea scores) across two dosage groups were compared using non-parametric Kruskal Wallis one-way analysis of variance. Mann Whitney U test was used to conduct sub-group analyses for comparing PONV scores and 4-point verbal descriptive nausea scale scores between two given groups. McNemar's test was done to compare differences in rates of complete response in a given dosage group across different time periods of assessment. Results: Our study results shows clear superiority of palonosetron with dexamethasone as a prophylactic drug for the prevention of PONV than that of granisetron with dexamethasone. Conclusions: Due to its longer duration of action, a single dose of palonosetron with dexamethasone before induction is effective in preventing PONV for upto 72 hours and hence can be termed as a prophylactic drug for PDNV also. It’s optimal and effective dose is 0.075mg i.v. with minimal side effects.

Knowledge and prevalence of sexually transmitted infections among female sex workers in Ahmedabad city.

Background & objectives: Sexually transmitted infections (STIs) continue to present major health, social and economic problems especially amongst Female Sex Workers (FSWs). Objectives : 1. To assess the knowledge of STIs among FSWs. 2. To find the prevalence of STIs among them and correlate it with various variable. Study method: A cross sectional study was carried out in the two Targeted Intervention areas working in the Ahmedabad city covering 10% of their total registered population. Results: Total 353 FWSs were covered. The mean age was 32.85+ 7.6 years. Majority was married and either illiterate or educated up to primary standards. Most common symptom of STI known to FSWs was Genital ulcer (67%) and 170 (48%) of FSWs had suffered from STI in last one year, out of them 128(75%) had taken the treatment. Eighty percent FSWs had consistently used condom in last 1 year. Risk of getting STI in 30 to 35 years age group was more than the overall risk (OR>1). The risk of STI was 7.85 times and 2.87 times more amongst the FSWs having duration of sex work < 10 years and those not using condom consistently, respectively. The difference of treatment seeking behavior with duration of sex work and knowledge of STI was highly significant (p<0.001). Conclusions: Knowledge of symptoms of STI was high. Although the condom use was claimed by the respondents still half of them suffered from STIs in last one year.

Knowledge of HIV/AIDS and HIV testing among the high risk groups (HRGs) population.

Background: Several factors put India in danger of experiencing rapid spread of HIV if effective prevention and control measures are not scaled up throughout the country. Aims & Objective: (1) To assess the level of basic knowledge about HIV/AIDS among the study population; (2) To analyze the HIV testing among them. Material and Methods: It was a cross sectional study carried out during April –May, 2010 amongst 3125 subjects of high risk groups (HRGs) comprising of IDUs (Injectable Drug Users), Female Sex workers (FSWs), MSMs (Male having Sex with Males) and Single Male Migrants (SMMs) covered by 13 Targeted Interventions (TIs) of Ahmedabad city. Ten percent of registered HRGs were assessed by systematic sampling. Data was analyzed using Epi info version 3.5.1. Results: Mean age of HRGs was 28.69 years and about half of HRGs were educated up to primary standard. More than half of them were married.85% HRGs had heard of HIV and 51% correctly knew what HIV positive means. Knowledge about AIDS was 76% and understanding of AIDS was 66% among them .About 38% HRGs knew that HIV is infectious and 72.8% knew that HIV is incurable. About 65% HRGs knew that there is no effective vaccine for HIV. About 65% HRGs had been tested ever tested and in last 6 months about 52.2% of HRGs were tested for HIV. Age and education were statistically significantly associated with the knowledge about incurability of HIV, non-existence of vaccine, and ever testing of HIV and in last six months also with disclosure of HIV positive status. Additionally age was also statistically significantly associated with infectious nature of HIV. Conclusion: Young and literate HRGs are better aware about the disease and are more concerned about their HIV status. They are also more open about disclosing their HIV/AIDS status.

Factors affecting sterilization operation among couples of a rural area in Ahmedabad: A record-based study.

Introduction: Various socio demographic factors play role in sterilization operation. Materials and Methods: A record-based study was conducted in Jetalpur, rural area of Ahmedabad District. Records of all sterilization operation done between April 2010 to March 2011 were studied. Results: A total of 180 sterilization operations were performed, of which 179 (99.4%) were female sterilization and one (0.6%) was vasectomy. The mean age of females was 28.27 years and that of their husbands was 31.72 years. Total 45% of females in the study population were illiterate, whereas 17% of their husbands were illiterate and their average family size was 2.8 members. Majority of females underwent sterilization operation when the age of last living child was between 1-5 years. In 67% cases, female health worker was the motivator. Only two couples had no living male child, whereas all other couples had at least one male child in the family. There was no significant relationship between the education of the mother and the age of the last living child, but education of mother was significantly related to the total number of living children in the family. Education of the father was significantly related with the age of last living child and the total number of living children in the family. Conclusion: The study reveals that education of both parents is an important driving factor in deciding the size of family. Majority of couple decide for permanent sterilization after having at least one male child. Thus, there is a strong preference for at least one male child in the family.