Therapeutic Efficacy of Nootropic Drugs — A Discussion of Clinical Phase III Studies with Nimodipine as a Model

AbstractAnticoagulation with oral antagonists without vitamin K (NOACs) is the preferred therapy for stroke prevention in atrial fibrillation. Vitamin K antagonists (VKA) should only be prescribed if there are contraindications to NOAC (e. g. mechanical heart valves, rheumatic mitral stenosis). The guideline recommendations are based on dedicated NOAC development programs with large randomized clinical phase III studies. Data from observational studies on the efficacy and safety of NOACs compared to VKA are in general complementary to data stemming from the phase III studies. Due to their pharmacokinetic and dynamic properties, NOACs are much easier to handle than VKA. Amongst other advantages, this implies that in case of short interruptions in anticoagulation therapy (e. g. for surgical procedures), bridging therapy with heparin is no longer required. This will reduce bleeding complications dramatically.

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1066-P: Comparison of Efficacy of Lixisenatide Combined with Basal Insulin with or without Metformin in Asian and Caucasian Patients with Type 2 Diabetes: A Pooled Analysis of Phase-III Studies

Diabetes ◽

10.2337/db20-1066-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 1066-P

Author(s):

REN YUEZHONG ◽

MINZHI LIU ◽

GUANGYU WU ◽

XIA ZHANG ◽

NAN CUI

Keyword(s):

Type 2 Diabetes ◽

Basal Insulin ◽

Pooled Analysis ◽

Phase Iii ◽

Caucasian Patients ◽

Phase Iii Studies

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Faculty Opinions recommendation of Safety and immunogenicity of a quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine in infants and toddlers: three multicenter phase III studies.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717953011.793458560 ◽

2012 ◽

Author(s):

Glenn Tillotson

Keyword(s):

Conjugate Vaccine ◽

Diphtheria Toxoid ◽

Phase Iii ◽

Infants And Toddlers ◽

Multicenter Phase ◽

Phase Iii Studies

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Comparative Efficacy Trials (Phase III Studies)

Wiley StatsRef: Statistics Reference Online ◽

10.1002/9781118445112.stat03694 ◽

2014 ◽

Author(s):

Judith D. Goldberg ◽

Yongzhao Shao

Keyword(s):

Phase Iii ◽

Comparative Efficacy ◽

Efficacy Trials ◽

Phase Iii Studies

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Matching comparisons of therapeutic efficacy suggest better clinical outcomes for patients treated with peginterferon beta-1a than with glatiramer acetate

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286420975916 ◽

2021 ◽

Vol 14 ◽

pp. 175628642097591

Author(s):

Thomas F. Scott ◽

Ray Su ◽

Kuangnan Xiong ◽

Arman Altincatal ◽

Carmen Castrillo-Viguera ◽

...

Keyword(s):

Clinical Trials ◽

Propensity Score ◽

Clinical Outcomes ◽

Glatiramer Acetate ◽

Therapeutic Efficacy ◽

Individual Patient Data ◽

Patient Data ◽

Phase Iii ◽

Lower Probability ◽

Phase Iii Clinical Trials

Background: Peginterferon beta-1a and glatiramer acetate (GA) are approved first-line therapies for the treatment of relapsing forms of multiple sclerosis, but their therapeutic efficacy has not been compared directly. Methods: Clinical outcomes at 2 years, including no evidence of disease activity (NEDA), for patients receiving peginterferon beta-1a 125 mcg every 2 weeks (Q2W) or GA 20 mg/ml once daily (QD) were compared by propensity score matching analysis using individual patient data from ADVANCE and CONFIRM phase III clinical trials. In addition, clinical outcomes at 1–3 years for patients receiving peginterferon beta-1a Q2W or GA 40 mg/ml three times a week (TIW) were evaluated using a matching-adjusted comparison analysis of individual patient data from ADVANCE and the ADVANCE extension study, ATTAIN, and aggregate patient data from the phase III GALA and the GALA extension studies. Results: Propensity-score-matched peginterferon beta-1a patients ( n = 336) had a significantly lower annualized relapse rate [ARR (0.204 versus 0.282); rate ratio = 0.724; p = 0.045], a significantly lower probability of 12-week confirmed disability worsening (10.0% versus 14.6%; hazard ratio = 0.625; p = 0.048), and a significantly higher rate of NEDA (20.3% versus 11.5%; p = 0.047) compared with GA 20 mg/ml QD patients after 2 years of treatment. Matching-adjusted peginterferon beta-1a patients (effective n = 276) demonstrated a similar ARR at 1 year (0.278 versus 0.318; p = 0.375) and significantly lower ARR at 2 years (0.0901 versus 0.203; p = 0.032) and 3 years (0.109 versus 0.209; p = 0.047) compared with GA 40 mg/ml TIW patients ( n = 834). Conclusion: Results from separate matching comparisons of phase III clinical trials and extension studies suggest that peginterferon beta-1a 125 mcg Q2W may provide better clinical outcomes than GA (20 mg/ml QD or 40 mg/ml TIW).

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Calcipotriene foam for the treatment of plaque-type psoriasis: Results of two phase III studies

Journal of the American Academy of Dermatology ◽

10.1016/j.jaad.2009.11.531 ◽

2010 ◽

Vol 62 (3) ◽

pp. AB138

Keyword(s):

Phase Iii ◽

Two Phase ◽

Plaque Type ◽

Phase Iii Studies

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Clinical and bacteriological efficacy of the ketolide telithromycin against isolates of key respiratory pathogens: a pooled analysis of phase III studies

Clinical Microbiology and Infection ◽

10.1111/j.1469-0691.2004.00752.x ◽

2004 ◽

Vol 10 (1) ◽

pp. 27-36 ◽

Cited By ~ 6

Author(s):

D.E. Low ◽

S. Brown ◽

D. Felmingham

Keyword(s):

Pooled Analysis ◽

Phase Iii ◽

Respiratory Pathogens ◽

Phase Iii Studies

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Bevacizumab and Breast Cancer: A Meta-Analysis of First-Line Phase III Studies and a Critical Reappraisal of Available Evidence

Journal of Oncology ◽

10.1155/2012/417673 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 50

Author(s):

José R. Rossari ◽

Otto Metzger-Filho ◽

Marianne Paesmans ◽

Kamal S. Saini ◽

Alessandra Gennari ◽

...

Keyword(s):

Breast Cancer ◽

Fixed Effects ◽

Meta Analysis ◽

Metastatic Breast ◽

Progression Free Survival ◽

Phase Iii ◽

First Line ◽

Statistical Estimates ◽

Treatment Indications ◽

Phase Iii Studies

Background. Randomized studies have shown different magnitude of bevacizumab benefit in the treatment of advanced breast cancer. Regulatory agencies have modified bevacizumab treatment indications across different regions. In this study, we perform a meta-analysis of phase III studies aiming to interrogate the magnitude of bevacizumab benefit for the treatment of first-line HER2-negative metastatic breast cancer (MBC).Methods. Data from studies E2100, AVADO and RIBBON-1 were used to calculate the benefit of bevacizumab in terms of tumor overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicities. Combined statistical estimates of hazard ratios (HR) and odds ratios were calculated using fixed-effects or random-effects models.Results. A total of 2,695 patients were evaluated. Combining bevacizumab with different chemotherapy backbones resulted in a 30% risk reduction of PFS events (HR = 0.70; 95% confidence interval [CI], 0.57–0.86) and increased ORR (odds ratio 1.81; 95% CI, 1.53–2.14). No OS benefit could be demonstrated (HR = 0.95; 95% CI, 0.85–1.06). Bevacizumab significantly increased the incidence of adverse events such as proteinuria, hypertension and cardiovascular events.Conclusions. Bevacizumab combined with chemotherapy in the first-line treatment of MBC significantly improved ORR and PFS, but also increased grade 3-4 toxicities. No significant OS advantage was observed.

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