Background: Desidustat (ZYAN1) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that stimulates erythropoiesis. Stabilizing HIF via PHI is developing as a new therapeutic approach to treat anemia secondary to chronic kidney disease (CKD). This trial evaluated the safety, tolerability, and efficacy of Desidustat in adult CKD patients with anemia, who were not on dialysis. Methods: This was a Phase 2, randomized, double-blind, 6-week, placebo-controlled, dose-ranging, safety and efficacy study. A total of 117 eligible patients were randomized to 4 arms: 100, 150, 200 mg, or placebo. The investigational product was administered every alternate day for 6 weeks in fasting conditions. The primary endpoint was change in hemoglobin (Hb) from baseline to week 6. Results: Baseline demographics were well balanced among all the treatment arms. In the modified intent-to-treat (mITT) population, a mean Hb increase of 1.57, 2.22, and 2.92 g/dL in Desidustat 100, 150, and 200 mg arms, respectively, was observed post 6 weeks treatment. The responder rate (≥1 g/dL increase) was 66% in 100 mg, 75% in 150 mg, and 83% in 200 mg treatment arms, in the mITT population. Eighteen patients had at least one treatment emergent adverse event (TEAE), and 5 patients reported at least one drug-related mild TEAE. No death or serious adverse event was reported during the trial. Conclusion: There was dose-related increase in Hb across all doses compared to placebo in mITT and per-protocol populations. Desidustat also increased pharmacokinetic parameters Cmax and AUC in dose-related manner. There was no significant change in vital signs, electrocardiographic parameters, or safety laboratory values. Clinical Trial Registration Number CTRI/2017/05/008534 (registered on May 11, 2017).

Background Limited supply, cost and potential for severe adverse effects observed with the blood derived rabies immunoglobulin products has led to search for alternative therapies. This issue has been addressed by developing an antirabies monoclonal antibody cocktail. Methods This is a phase 3, randomized, open-label, noninferiority trial conducted in patients with WHO category III exposure with suspected rabid animal. Eligible patients were assigned to either the test arm, TwinrabTM (docaravimab and miromavimab) or the reference arm, Human rabies immunoglobulin (HRIG; Imogam® Rabies-HT), in a ratio of 1:1. The primary endpoint was the comparison of responder rates between the two arms assessed as percentage of those with rabies virus neutralizing antibodies titers ≥ 0.5 IU/mL on day 14. Results A total of 308 patients were equally randomized into the two arms. In the per-protocol (PP) population, there were 90.21% responders in the TwinrabTM arm and, 94.37% in the HRIG arm. The Geometric Mean of RFFIT titres in the PP on day 14 were 4.38 and 4.85 IU/mL, for the TwinrabTM and HRIG arms, respectively. There were no deaths or serious adverse events reported. Conclusions This study confirmed that TwinrabTM is non-inferior to HRIG in terms of providing an unbroken window of protection up to day 84. This trial in healthy adults with WHO category III exposure from suspected rabid animal also establishes the safety of TwinrabTM in patients with one WHO approved vaccine regimen (Essen). Trials Registration CTRI/2017/07/009038

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Background: Frail, old patients with and without cognitive impairment are at high risk of falls and associated medical and psychosocial issues. The Modified Falls Efficacy Scale (MFES) was developed to assess fear of falling and it is shown to be a reliable and valid measure of falls self-efficacy in western countries. The lack of adequate, validated instruments has partly hindered research in this field. Methodology: The 'forward-backward' translation procedure was applied to translate the MFES into Hindi and Gujarati. Harmonization was done by expert panel review and pilot testing over 10 subjects. The questionnaires were then finalized.98 participants (70-Gujarati MFES; 28-Hindi MFES), meeting inclusion-exclusion criteria and willing to participate were included in the study. Interview regarding general health and fall history was taken. Gujarati MFES and Hindi MFES data were collected and Berg Balance Scale was performed. Results: The analysis of internal validity of the Gujarati and Hindi MFES revealed that the scale items presented adequate internal consistency (Cronbach's alpha: Gujarati MFES-0.993, Hindi MFES-0.992).The Gujarati MFES showed strong positive correlation with BBS (r=0.820, P value=0.000) and a strong negative correlation with age (r=-0.351, P value=0.003). The Hindi MFES showed a moderate positive correlation with BBS (r=0.565, P value=0.002) and a weak negative correlation with age (r=-0.297, P value= 0.125). Conclusion: The Gujarati version of MFES is a valid and measure to estimate fall-related efficacy in older adults who have Gujarati as their first language. The Hindi version of MFES shall have its validity established with a larger sample size.

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