The Bioequivalence of Tafamidis 61 ‐mg Free Acid Capsules and Tafamidis Meglumine 4 × 20‐mg Capsules in Healthy Volunteers

AbstractTafamidis, a non ‐nonsteroidal anti‐inflammatory benzoxazole derivative, acts as a transthyretin (TTR) stabilizer to slow progression of TTR amyloidosis (ATTR). Tafamidis meglumine, available as 20‐mg capsules, is approved in more than 40 countries worldwide for the treatment of adults with early‐stage sympt omatic ATTR polyneuropathy. This agent, administered as an 80‐mg, once‐daily dose (4 × 20‐mg capsules), is approved in the United States, Japan, Canada, and Brazil for the treatment of hereditary and wild‐type ATTR cardiomyopathy in adults. An alternative single solid oral dosage formulatio n (tafamidis 61‐mg free acid capsules) was developed and introduced for patient convenience (approved in the United States, United Arab Emirates, and European Union). In this single‐center, open‐label, randomized, 2‐period, 2‐sequence, crossover, multiple‐dose phase 1 study, the rate and extent of absorption were compared between tafamidis 61‐mg free acid capsules (test) and tafamidis meglumine 80‐mg (4 × 20‐mg) capsules (reference) after 7 days of repeated oral dosing under fasted conditions in 30 healthy volunteers. Ratios of adjusted geometric means (90%CI) for the test/r eference formulations were 102.3 (98.0‐106.8) for area under the concentration‐time profile over the dosing interval and 94.1 (89.1‐99.4) for the maximum observed concentration, satisfying prespecified bioequivalence acceptance criteria (90%CI, 80‐125). ...
Source: Clinical Pharmacology in Drug Development - Category: Drugs & Pharmacology Authors: Tags: Original Manuscript Source Type: research

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Contributors : Gian L Vita ; M'Hammed Aguennouz ; Francesca Polito ; Rosaria Oteri ; Massimo Russo ; Luca Gentile ; Cristina Barbagallo ; Marco Ragusa ; Carmelo Rodolico ; Rosa M Di Giorgio ; Antonio Toscano ; Giuseppe Vita ; Anna MazzeoSeries Type : Non-coding RNA profiling by arrayOrganism : Homo sapiensTransthyretin variant amyloidosis (ATTRv) is a rare autosomal dominant disease characterized by the accumulation of amyloid in many organs, mostly causing a sensory-motor neuropathy, cardiomyopathy, and dysautonomia. The aim of the study was to report microRNAs (miRNAs) expression profile identified in the blood of ATTRv ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Non-coding RNA profiling by array Homo sapiens Source Type: research
Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized infiltrative cardiomyopathy in which conduction system disease is common. The aim of our study was to define the incidence and prevalence of high-grade atrioventricular (AV) block requiring pacemaker implantation in our quaternary referral center. This was a single-center retrospective cohort study of 369 consecutive patients with ATTR-CA who underwent 12-lead electrocardiogram (ECG) at the time of ATTR-CA diagnosis. During a mean follow-up of 28 months, serial ECGs and the electronic medical record were examined for the development of high-grade AV ...
Source: The American Journal of Cardiology - Category: Cardiology Authors: Source Type: research
Abstract Cardiac amyloidosis, the majority of cases of which are due to immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR), affects different aspects of the heart and cardiovascular system. Amyloid-induced cardiomyopathy, clinically manifesting with heart failure and electrophysiological abnormalities, has distinct characteristics compared to non-amyloid cardiomyopathies. Accordingly, specific management strategies are required. This paper will review the cardiovascular manifestations of patients with cardiac amyloidosis and their suggested treatment strategies, emphasizing the import...
Source: Acta Haematologica - Category: Hematology Authors: Tags: Acta Haematol Source Type: research
A new study investigates echocardiographic phenotypes of transthyretin cardiac amyloidosis, the most common etiology of restrictive cardiomyopathy, identifying parameters predictive of survival.European Heart Journal
Source: Medscape Today Headlines - Category: Consumer Health News Tags: Cardiology Journal Article Source Type: news
This study evaluated the diagnostic value of the novel cardiovascular magnetic resonance (CMR) parameter “myocardial transit-time” (MyoTT) in distinguishing cardiac amyloidosis from other hypertrophic cardiomyopathies.MethodsN  = 20 patients with biopsy-proven cardiac amyloidosis (CA),N  = 20 patients with known hypertrophic cardiomyopathy (HCM), andN  = 20 control patients without relevant cardiac disease underwent dedicated CMR studies on a 1.5-T MR scanner. The CMR protocol comprised cine and late-gadolinium-enhancement (LGE) imaging as well as first-pass perfusion a...
Source: Clinical Research in Cardiology - Category: Cardiology Source Type: research
AbstractPurpose of ReviewTransthyretin amyloidosis is an increasingly recognized cause of restrictive cardiomyopathy related to amyloid fibril deposition in cardiac tissues. As treatment therapies have emerged for transthyretin amyloidosis (ATTR), so has interest in using biomarkers to identify disease prior to advanced presentation.Recent FindingsLower levels of transthyretin and retinol binding protein-4 have been demonstrated in patients with pathogenic mutations of transthyretin either with or without clinical disease. Levels associate with the severity of mutations as well as response to treatment with transthyretin s...
Source: Current Heart Failure Reports - Category: Cardiology Source Type: research
Opinion statementCardiac amyloidosis is associated with a high mortality rate, a long delay between the first signs and the diagnosis but a short interval between diagnosis and death. This scenario has changed recently due to improved disease awareness among doctors and significant progress in diagnosis thanks to multimodal imaging and a multidisciplinary approach. Therefore, during the last few years, we have had access to specific therapies for those patients. Those therapies are quite different depending on the type of amyloidosis, but there has been real progress. Systemic light chain amyloidosis (AL) with cardiac invo...
Source: Current Treatment Options in Oncology - Category: Cancer & Oncology Source Type: research
Amyloid transthyretin (ATTR) cardiac amyloidosis (CA) is an increasingly recognized cause of restrictive cardiomyopathy and associated heart failure with preserved ejection fraction (HFpEF). Despite improved diagnostic techniques to identify this condition, many patients experience delayed diagnosis. Interpretation of routine cardiac biomarkers (i.e. troponins and brain natriuretic peptide (BNP)) and echocardiography in ATTR-CA is limited, particularly in relation to pyrophosphate (PYP) scintigraphy.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: (64) Source Type: research
Advanced amyloid cardiomyopathy (ACM) patients have high waitlist (WL) mortality. Given the greater emphasis and clarity for status exceptions for ACM patients in the new allocation system, we sought to assess whether this change in the allocation policy would affect the WL and post-transplant outcomes in ACM pts.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: (660) Source Type: research
Publication date: March–April 2020Source: Heart &Lung, Volume 49, Issue 2Author(s): Spencer Guthrie
Source: Heart and Lung: The Journal of Acute and Critical Care - Category: Respiratory Medicine Source Type: research
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