Linomide in the treatment of multiple sclerosis: MRI results from prematurely terminated phase-III trials

2000 ◽  
Vol 6 (2) ◽  
pp. 99-104 ◽  
Author(s):  
I L Tan ◽  
G J Lycklmaà Nijeholt ◽  
C H Polman ◽  
H J Adér ◽  
F Barkhof ◽  
...  
Keyword(s):  
Rebound Effect ◽  
Phase Iii ◽  
Outcome Parameter ◽  
Two Phase ◽  
Treatment Groups ◽  
Secondary Progressive ◽  
Significant Difference ◽  
Relapsing Remitting ◽  
Phase Iii Trials ◽  
Modest Effect

Due to an unexpected increase in serious cardiovascular event in MS patient treated with Linomide, a synthetic immunomodulator, two phase-III multinational relapsing remitting (RR) and secondary progressive (SP) MS trials had to be discontinued. MRI result of 413 patient who participated for at least 3 months were analysed. Patient received placebo, 2.5 or 5 mg Linomide. Scans were performed at pre-enrolment, month 3 and termination. The number and volume of enhancing lesions (ELV), and the number of active scans were evaluated At month 3, the decrease in the number of enhancing lesions in the placebo group was I I1%, compared with 15% in the 2.5 mg group (P=0.027) and 23% in the 5 mg group (P=0.057). Using the percentage of active scans as outcome parameter, the odds ratio for improvement between placebo and 2.5 mg group was 1.62 (P=0.14); between placebo and 5 mg Linomide group 3.58 (P=0.003). At termination, a rebound effect was noted in the 2.5 mg group (P=0.0 1). Analysis of the ELV showed no significant difference between placebo and treatment groups. Although Linomide has unacceptable side effect, it seems to have a modest effect on MS disease activity, as measured by MRI.

scholarly journals Comparative Susceptibilities to Fidaxomicin (OPT-80) of Isolates Collected at Baseline, Recurrence, and Failure from Patients in Two Phase III Trials of Fidaxomicin against Clostridium difficile Infection

2011 ◽  
Vol 55 (11) ◽  
pp. 5194-5199 ◽  
Author(s):  
Ellie J. C. Goldstein ◽  
Diane M. Citron ◽  
Pamela Sears ◽  
Farah Babakhani ◽  
Susan P. Sambol ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Restriction Endonuclease Analysis ◽  
Phase Iii ◽  
Two Phase ◽  
Double Blind ◽  
Single Strain ◽  
Content Type ◽  
Treatment Groups ◽  
Phase Iii Trials ◽  
Intent To Treat

ABSTRACTA 10-day course of oral fidaxomicin (200 mg twice a day [b.i.d.]), a potent new macrocyclic drug, was compared to vancomycin (125 mg four times a day [q.i.d.]) in 1,164 adults (1,105 in the modified intent-to-treat [mITT] population) withClostridium difficileinfection in two phase III randomized, double-blind trials at sites in North America and 7 European countries. Of 1,105 mITT patients, 792 (71.7%), including 719/999 (72.0%) in the per-protocol (PP) population, provided aC. difficilestrain at baseline, of whom 356 received fidaxomicin with 330 cures (92.7%) and 363 received vancomycin with 329 cures (90.6%). The susceptibilities (MIC90) of baseline isolates did not predict clinical cure, failure, or recurrence for fidaxomicin (MIC90, 0.25 μg/ml for both; range, ≤0.007 to 1 μg/ml), but there was a one-dilution difference in the MIC90(but not the MIC50) for vancomycin (MIC90, 2 μg/ml [range, 0.25 to 8 μg/ml] for cure and 4.0 μg/ml [range, 0.5 to 4 μg/ml] for failures). A total of 65 (7.9%) “rifaximin-resistant” (MIC > 256 μg/ml) strains were isolated in both treatment groups on enrollment, which increased to 25% for failures at the end of therapy. No resistance to either fidaxomicin or vancomycin developed during treatment in either of the phase III studies, although a single strain isolated from a cured patient had an elevated fidaxomicin MIC of 16 μg/ml at the time of recurrence. All isolates were susceptible to ≤4 μg/ml of metronidazole. When analyzed by restriction endonuclease analysis (REA) type, 247/719 (34.4%) isolates were BI group isolates, and the MICs were generally higher for all four drugs tested (MIC90s: fidaxomicin, 0.5; vancomycin, 2.0; metronidazole, 2.0; and rifaximin, >256 μg/ml) than for the other REA types. There was no correlation between the MIC of a baseline clinical isolate and clinical outcome. MIC90s were generally low for fidaxomicin and vancomycin, but BI isolates had higher MICs than other REA group isolates.

scholarly journals Long-term Outcomes of Ranibizumab Therapy for Diabetic Macular Edema: The 36-Month Results from Two Phase III Trials

Ophthalmology ◽  
2013 ◽  
Vol 120 (10) ◽  
pp. 2013-2022 ◽  
Author(s):  
David M. Brown ◽  
Quan Dong Nguyen ◽  
Dennis M. Marcus ◽  
David S. Boyer ◽  
Sunil Patel ◽  
...  
Keyword(s):  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Phase Iii ◽  
Long Term Outcomes ◽  
Two Phase ◽  
Phase Iii Trials

scholarly journals Pharmacotherapy Options for Multiple Sclerosis: Focus on Natalizumab

2010 ◽  
Vol 2 ◽  
pp. CMT.S2043 ◽  
Author(s):  
Martin Stangel ◽  
Bernd C. Kieseier
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
Safety Management ◽  
Jc Virus ◽  
Unmet Need ◽  
Neurological Impairment ◽  
Phase Iii ◽  
First Line ◽  
Two Phase ◽  
Phase Iii Trials

Multiple sclerosis (MS) is considered an autoimmune disease causing demyelination in the central nervous system (CNS) that subsequently leads to axonal damage and neurological impairment. Currently available first line therapies are based on immunomodulation with beta-interferons or glatirameracetate. However, these treatments are only partially effective, thus, more powerful therapies represent an unmet need in MS. Natalizumab is a monoclonal antibody targeting the α4β1 integrin that has been shown to be crucial in the process of transmigration of immunocompetent cells across the blood-brain-barrier (BBB) into the CNS. Two phase III trials have demonstrated clinical and paraclinical efficacy of natalizumab and recent data suggest that many patients that have failed on a first-line disease modifying drug (DMD) benefit from a treatment with natalizumab. Unfortunately, since the licensing of natalizumab in 2006 there have been 75 cases of progressive multifocal leukoencephalopathy (PML) reported. This rare, but potentially fatal infection of the brain by JC-virus restricts the use of natalizumab. Currently there are attempts to define algorithms based on the identification of risk factors for the development of PML to achieve a better safety management for MS patients treated with this monoclonal antibody.

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