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Objective Presentation of pooled analysis of safety data for fremanezumab in patients with chronic (CM) or episodic migraine (EM) from 4 placebo‐controlled phase 2b and phase 3 studies. Background There is a need for an effective...
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Objective Presentation of pooled analysis of safety data for fremanezumab in patients with chronic (CM) or episodic migraine (EM) from 4 placebo‐controlled phase 2b and phase 3 studies. Background There is a need for an effective, safe, and well‐tolerated preventive therapy that specifically targets the pathophysiology of migraine to reduce the frequency and severity of migraine attacks in patients with CM or EM who experience 4 or more migraine days per month. Fremanezumab is a fully humanized monoclonal antibody that targets calcitonin gene‐related peptide, a neuropeptide involved in the pathophysiology of migraine. Design/Methods The 4 placebo‐controlled phases 2b and 3 studies included in this analysis were 16‐week, multicenter, randomized, double‐blind, placebo‐controlled, and parallel‐group studies consisting of a screening visit, a 28‐day pretreatment baseline period, and a 12‐week treatment period with a final evaluation 4?weeks after the final dose of the study drug. Safety endpoints included adverse events (AEs) and immunogenicity. Results A total of 2566 patients were randomized across all studies (fremanezumab, n?=?1704; placebo, n?=?862), and 2563 patients were treated. Common reasons for study discontinuation were withdrawal by patient (n?=?78), patient lost to follow‐up (n?=?60), and AE (n?=?50). The mean (standard deviation) duration of exposure was 83.8 (13.6) days for the patients who received fremanezumab, with a total exposure of 390.4 patient years and maximum exposure of 181?days. AEs were mostly mild to moderate in severity and were reported among 48‐69% of patients in all treatment groups, and most were injection site reactions (pain, induration, and erythema). Two deaths occurred (chronic obstructive pulmonary disease and intentional overdose of diphenhydramine), both of which were deemed unrelated to study drug by the investigators and sponsor. Cardiovascular adverse events, abnormal liver function tests, and hypersensitivity were uncommon and occurred at similar rates between the placebo and fremanezumab groups. Conclusions Fremanezumab is a generally safe and well‐tolerated preventive therapy for migraine in adults.
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Clobazam is a commonly used long-acting benzodiazepine approved by the US Food and Drug Administration (FDA) to treat seizures associated with Lennox Gastaut syndrome. The FDA approved maximum dosage of clobazam is 1 mg/kg/d or a ...
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Clobazam is a commonly used long-acting benzodiazepine approved by the US Food and Drug Administration (FDA) to treat seizures associated with Lennox Gastaut syndrome. The FDA approved maximum dosage of clobazam is 1 mg/kg/d or a total of 40 mg a day. Many providers exceed this dosage but there is limited data on the safety, tolerability, and efficacy of supratherapeutic doses. We reviewed retrospective data at our institution and compared patients on supratherapeutic doses to patients on therapeutic doses. A total of 133 patients met inclusion criteria (65 supratherapeutic, 67 therapeutic). There was no statistically significant difference in terms of seizure control, health care utilization, or side effects between patients on supratherapeutic doses and those on therapeutic doses. This study lends further support to the safety and tolerability of supratherapuetic doses of clobazam.
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Some strains of species belonging to the genera Bifidobacterium and Lactobacillus are used in order to maintain health. Although these organisms have a long record of safe use, it is important to assess their safety and tolerance ...
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Some strains of species belonging to the genera Bifidobacterium and Lactobacillus are used in order to maintain health. Although these organisms have a long record of safe use, it is important to assess their safety and tolerance in potentially vulnerable populations, such as infants. The objective of this study was to evaluate the safety and tolerance of three probiotic strains (Bifidobacterium longum subsp. infantis R0033, Bifidobacterium bifidum R0071 and Lactobacillus helveticus R0052) in healthy infants aged 3 to 12 months. A multi-centre randomized, double-blind, placebo-controlled intervention study with 221 healthy full-term infants was conducted. Infants received either a placebo or one of the 3 probiotic strains (3x10(9) cfu) daily during an 8 week intervention period. Growth (weight, height and head circumference), adverse events (AEs)/serious adverse events (SAEs), concentrations of D-lactic acid in urine samples, characteristics of the stools and use of medication were collected for safety evaluation. All 4 groups were homogeneous with respect to age, gender, feeding type, ethnicity, height, weight and head circumference at the start of the study. The results showed that changes in growth (weight, height and head circumference) were equivalent in all 4 groups. No SAEs were reported. Total number of AEs recorded was equivalent in all groups. Thus, the use of B. infantis R0033, L. helveticus R0052 and B. bifidum R0071 in infancy is safe, and well tolerated.
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Some strains of species belonging to the genera Bifidobacterium and Lactobacillus are used in order to maintain health. Although these organisms have a long record of safe use, it is important to assess their safety and tolerance ...
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Some strains of species belonging to the genera Bifidobacterium and Lactobacillus are used in order to maintain health. Although these organisms have a long record of safe use, it is important to assess their safety and tolerance in potentially vulnerable populations, such as infants. The objective of this study was to evaluate the safety and tolerance of three probiotic strains (Bifidobacterium longum subsp. infantis R0033, Bifidobacterium bifidum R0071 and Lactobacillus helveticus R0052) in healthy infants aged 3 to 12 months. A multi-centre randomized, double-blind, placebo-controlled intervention study with 221 healthy full-term infants was conducted. Infants received either a placebo or one of the 3 probiotic strains (3x10(9) cfu) daily during an 8 week intervention period. Growth (weight, height and head circumference), adverse events (AEs)/serious adverse events (SAEs), concentrations of D-lactic acid in urine samples, characteristics of the stools and use of medication were collected for safety evaluation. All 4 groups were homogeneous with respect to age, gender, feeding type, ethnicity, height, weight and head circumference at the start of the study. The results showed that changes in growth (weight, height and head circumference) were equivalent in all 4 groups. No SAEs were reported. Total number of AEs recorded was equivalent in all groups. Thus, the use of B. infantis R0033, L. helveticus R0052 and B. bifidum R0071 in infancy is safe, and well tolerated.
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Abstract Ergot is a fungal disease of many plants but is perhaps most commonly associated with domesticated grasses or cereals, such as rye, wheat, barley, oat, sorghum, millet, maize and rice. Ergot is of historical significance,...
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Abstract Ergot is a fungal disease of many plants but is perhaps most commonly associated with domesticated grasses or cereals, such as rye, wheat, barley, oat, sorghum, millet, maize and rice. Ergot is of historical significance, having been reported for several millennia, but is also of concern in modern agricultural production systems. Caused by many different species within the genus Claviceps, the fungi cause the production of sclerotia, which are typically dark in colour, in place of healthy grain. The sclerotia contain toxins that can make the grain unsafe for consumption by humans or livestock. Ergot can be managed both preharvest as well as postharvest to minimize the presence of sclerotia and their associated toxins in food and feed systems. In this review, we provide a detailed update on our current knowledge of ergot on cereals, with a focus on recent advances in our understanding of fungal toxins and their regulation, pathogen biology and disease management.
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Purpose: The aim of this study was to evaluate the safety, tolerability, and pharmacokinetic parameters of up to 15 dose levels of ONO-4232, a selective agonist for the EP4 subtype of the prostaglandin E-2 receptor, with a dual le...
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Purpose: The aim of this study was to evaluate the safety, tolerability, and pharmacokinetic parameters of up to 15 dose levels of ONO-4232, a selective agonist for the EP4 subtype of the prostaglandin E-2 receptor, with a dual left ventricular lusitropic and venodilatory action, in healthy, adult, male and female volunteers.
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Abstract This study investigated ethnic differences in the safety, tolerability, pharmacokinetics, and pharmacodynamics of GSK2831781, an anti–lymphocyte activation gene 3 (LAG3) monoclonal antibody, in healthy participants, and ...
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Abstract This study investigated ethnic differences in the safety, tolerability, pharmacokinetics, and pharmacodynamics of GSK2831781, an anti–lymphocyte activation gene 3 (LAG3) monoclonal antibody, in healthy participants, and determined local tolerability and bioavailability following subcutaneous (SC) administration. A double‐blind, randomized study of (A) single intravenous (IV) doses of GSK2831781 450?mg or placebo in Japanese and White participants; and (B) single SC doses of GSK2831781 150 or 450?mg, or placebo in White participants, was conducted. Blood samples for analyses were collected before dosing and over 112 days after dosing. GSK2831781 was well tolerated in Japanese and White participants after both IV and SC doses, with the adverse event profile in Japanese being consistent with other populations. There were no injection site adverse events. There was no evidence of differences in systemic exposure among Japanese and White participants. Systemic exposure did not vary with body weight. SC bioavailability was 76.5%, as estimated using population pharmacokinetic modeling. Full and sustained target engagement and evidence of LAG3+ cell depletion (≈53%–66%) were observed in both populations and after both administration routes. No evidence of reduced circulating regulatory T cells (CD4+CD25+CD127lowFoxP3+) was observed. Following IV and SC administration, GSK2831781 depleted circulating LAG3+ T cells with no interethnic difference observed. There were no major impacts on circulating regulatory T cells.
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Abstract Objective A novel topical cream was developed to address the appearance of aging periorbital skin. The goal of this study was to evaluate the efficacy and tolerability of this product (Total Eye? Firm & Repair Cream; Colorescience, Inc...
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Abstract Objective A novel topical cream was developed to address the appearance of aging periorbital skin. The goal of this study was to evaluate the efficacy and tolerability of this product (Total Eye? Firm & Repair Cream; Colorescience, Inc., Carlsbad, CA) for improving periorbital wrinkles, dryness, laxity, and dark circles. Methods This 8‐week open‐label trial enrolled subjects 35–65?years old seeking periocular rejuvenation (N?=?25; 22 female, 3 male). The product was applied each morning and evening after facial cleansing. Study endpoints were changes in Investigator Clinical Grading and Eye Appearance Assessments, Subject Self‐assessment Questionnaires, and tolerability after 4 and 8?weeks of treatment. Results Among subjects completing the study (n?=?23), all (100%) showed some global improvement at Weeks 4 and 8 and almost half (48%) achieved moderate or marked improvement. Improvements were observed for all parameters and were most pronounced for wrinkles, laxity, and dark circles. Improvements for laxity and dryness were significant by Week 4 and for dark circles by Week 8. At Week 8, subjects agreed or strongly agreed that the product made their eyes feel more hydrated (100%), look and feel healthier (95%), and increased confidence in their eye appearance (91%). The product was well‐tolerated. Limitations Modest number of subjects and open‐label study design. Conclusion Twice‐daily Total Eye? Firm & Repair Cream improved the overall appearance of the periorbital area. The product was well‐tolerated and most treated subjects were satisfied with their results. The product is a viable option for treating periorbital wrinkles and laxity and should be considered a safe and effective skincare option.
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Background: A 12-month, open-label extension study assessed the long-term safety and tolerability of lisdexamfetamine dimesylate (LDX) in adults with binge eating disorder (BED).
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Angiotensin receptor blocker and a neprilysin inhibitor (ARNI) has emerged as an innovative therapy for patients of heart failure with reduced ejection fraction (HFrEF). The purpose of this study was to assess the safety and toler...
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Angiotensin receptor blocker and a neprilysin inhibitor (ARNI) has emerged as an innovative therapy for patients of heart failure with reduced ejection fraction (HFrEF). The purpose of this study was to assess the safety and tolerability of Sacubitril/Valsartan in patient with HFrEF in Pakistani population.This proof-of-concept, open label non-randomized clinical trial was conducted at a tertiary care cardiac center of Karachi, Pakistan. Patients with HFrEF were prescribed with Sacubitril/Valsartan and followed for 12 weeks for the assessment of safety and tolerability. Safety measures included incidence of hypotension, renal dysfunction, hyperkalemia, and angioedema.Among the 120 HFrEF patients, majority were male (79.2%) with means age of 52.73 ± 12.23 years. At the end of 12 weeks, four (3.3%) patients died and eight (6.7%) dropped out of the study. In the remaining 108 patients, 80.6% (87) of the patients were tolerant to the prescribed dose. Functional class improved gradually with 75.0% (81) in class I and 24.1% (26) in class II, and only one (0.9%) patient in class III at the end of 12 weeks. Hyperkalemia remains the main safety concern with incidence rate of 21.3% (23) followed by hypotension in 19.4% (21), and renal dysfunction in 3.7% (4) of the patients.Sacubitril/Valsartan therapy in HFrEF patients is safe and moderately tolerated among the Pakistani population. It can be used as first line of treatment for these patients.NCT05387967. Registered 24 May 2022—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05387967
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