scholarly journals Rosiglitazone Monotherapy in Mild-to-Moderate Alzheimer’s Disease: Results from a Randomized, Double-Blind, Placebo-Controlled Phase III Study

2010 ◽  
Vol 30 (2) ◽  
pp. 131-146 ◽  
Author(s):  
Michael Gold ◽  
Claire Alderton ◽  
Marina Zvartau-Hind ◽  
Sally Egginton ◽  
Ann M. Saunders ◽  
...  
2021 ◽  
Author(s):  
Letícia Escorse Requião ◽  
Giulia Freitas ◽  
Mayanna Macedo ◽  
Hanny Gondim ◽  
Blenda Antunes ◽  
...  

Introduction: Alzheimer’s disease (AD) is the main form of senile dementia. Most of the supposedly disease-modifying treatments in development are directed against the β-amyloid peptide, the administration of exogenous anti-Aβ monoclonal antibodies is a passive immunization strategy aimed at resolving the aggregation of this substance. Objective: Analyze the effectiveness of monoclonal antibodies in the treatment of Alzheimer’s disease. Methods: This is a literature review, based on randomized clinical trials published between 2014 and 2021. The search was conducted in the PubMed database. Results: According to the eligibility criteria, 10 articles were selected. Two of the randomized, double-blind, placebo-controlled phase III studies, one published in 2018 and the other published in 2016, evaluated the intervention with Solanezumab and Bapineuzumab, respectively. Both were not shown to be statistically significant (P = 0.10) for the outcome improvement of the score in the cognitive subscale of 14 and 11 items “Alzheimer’s Disease Assessment Scale” (ADAS-cog14 / 11). However, in a phase II randomized placebo-controlled clinical trial, published in 2021, the use of Donanemab in patients with early Alzheimer’s disease resulted in statistically significant cognitive and functional improvement (P = 0.04) for the outcome change in the scale “Integrated Alzheimer’s Disease Rating” (iADR). Conclusion: Although the use of Donanemab has resulted in cognitive and functional improvement, randomized, double-blind, placebo-controlled, phase III clinical trials need to be conducted to prove the efficacy and safety of its use in clinical practice. Other monoclonal antibodies evaluated did not demonstrate evidence of benefit.


BMJ Open ◽  
2014 ◽  
Vol 4 (10) ◽  
pp. e006364 ◽  
Author(s):  
Brian Lawlor ◽  
Sean Kennelly ◽  
Sarah O'Dwyer ◽  
Fiona Cregg ◽  
Cathal Walsh ◽  
...  

IntroductionThis study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82 weeks with a treatment period of 78 weeks.Methods and analysisAdult patients, males and females over 50 years with mild-to-moderate AD as defined by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease and Related Disorders Association (NINCDS-ADRDA) criteria, will be included in the study. It aims to recruit a total of 500 patients with AD; 250 in the nilvadipine group and 250 in the placebo group. Participants will be randomised to receive nilvadipine, an 8 mg overencapsulated, sustained release capsule, or a matching overencapsulated placebo (sugar pill) for a period of 78 weeks of treatment. The primary efficacy outcome measure in this study is the change in cognitive function as assessed by the Alzheimer's disease Assessment Scale (ADAS-Cog 12) from baseline to the end of treatment duration (78 weeks). There are two key secondary outcome measures, the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb) and the Disability Assessment for Dementia (DAD). If a statistically significant effect is seen in the primary outcome, CDR-sb will be considered to be a coprimary end point and only the DAD will contribute to the secondary outcome analysis.Ethics and disseminationThe study and all subsequent amendments have received ethical approval within each participating country according to national regulations. Each participant will provide written consent to participate in the study. All participants will remain anonymised throughout and the results of the study will be published in an international peer-reviewed journal.Trial registration numberEUDRACT Reference Number: 2012-002764-27.


2012 ◽  
Vol 4 (5) ◽  
pp. 43 ◽  
Author(s):  
John M Ringman ◽  
Sally A Frautschy ◽  
Edmond Teng ◽  
Aynun N Begum ◽  
Jenny Bardens ◽  
...  

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Shifu Xiao ◽  
Piu Chan ◽  
Tao Wang ◽  
Zhen Hong ◽  
Shuzhen Wang ◽  
...  

Abstract Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. Conclusions GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. Trial registration ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014


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