Estudio primario

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A MULTI-CENTRE,RANDOMISED,DOUBLE BLIND,PLACEBO CONTROLLED,PARALLEL GROUP STUDY TO INVESTIGATE EFFICACY AND SAFETY OF ONO-2506PO COMPARED TO PLACEBO,IN THE PRESENCE OF RILUZOLE,TO PATIENTS DIAGNOSED WITH AMYOTROPHIC LATERAL SCLEROSIS(ALS), WHO HAVE HAD ONSET OF MUSCLE WEAKNESS WITHIN 14 MONTHS OF RANDOMISATION

Año 2006
Autores [No se listan los autores]
Registro de estudios EU Clinical Trials Register
Enlaces EUCTR

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INTERVENTION:

Product Name: ONO‐2506PO Product Code: ONO‐2506PO Pharmaceutical Form: Capsule, soft INN or Proposed

INN:

Arundic Acid CAS Number: 185517‐21‐9 Current Sponsor code: ONO‐2506 Other descriptive name: (2R)‐2‐Propyloctanoic acid Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 300‐ Pharmaceutical form of the placebo: Capsule, soft Route of administration of the placebo: Oral use

CONDITION:

Amyotrophic Lateral Sclerosis ; MedDRA version: 8.1 Level: LLT Classification code 10002026 Term: Amyotrophic lateral sclerosis

PRIMARY OUTCOME:

Main Objective: The primary objective of this trial will be to evaluate the effect of ONO‐2506PO(1200 mg once daily) on the slope of respiratory function (slow vital capacity (SVC) expressed as a percentage of the predicted value) over 12 months compared with placebo group. Primary end point(s): The primary efficacy endpoint is defined as the slope of respiratory function (SVC expressed as a percentage of the predicted value) over 12 months. Secondary Objective: The secondary objectives of this trial will be to evaluate the effect of ONO‐2506PO(1200mg once daily) on:; Respiratory Function:; The slope of respiratory function(SVC expressed as a percentage of the predicted value) over 18 months; Time to SVC reaching below 50% of the predicted value over 12 and 18 months; Survival:; Survival (defined as death) over 12 and 18 months ; Death, tracheotomy or permanent assisted ventilation over 12 and 18 months; Functional status:; The slope of functional status using the ALS Functional Rating Scale(ALSFRS‐R)over 12 and 18 months; Time to loss of function using ALSFRS‐R over 12 and 18 months; Muscle Strength:; The slope of muscle strength using MRC muscle score over 12 and 18 months; Quality of life:; Quality of life (QoL) using EuroQoL (EQ‐5D) over 12 and 18 months; Safety and Tolerability:; Vital signs,Physical examination,weight,12‐Lead ECG, clinical laboratory tests and adverse events monitoring;

INCLUSION CRITERIA:

1)Adult males and females aged 18 to 75 years 2)Diagnosis of clinically possible, clinically probable laboratory‐supported, clinically probable,or clinically definite ALS(according to WNF EL Escorial diagnostic criteria, revised according to the Airlie House Conference 1998) 3)Onset of muscle weakness within 14 months of randomisation 4)Baseline SVC greater than or equal to 70% of predicted normal at Visit 1 (screening visit) 5)Concomitant standard Riluzole therapy (50mg twice daily) for at least 2 weeks prior to Visit 1 (screening visit),with liver function test(LFT) results within two times the upper limit of the normal range 6)Ability to swallow without the requirement for nasogastric or percutaneous endoscopic gastrostomy(PEG) feeding as evidenced by a score of = 3 on ALSFRS‐R question# c (swallowing) at Visit 1 (screening visit) 7)Agreement for themselves or their partner to use an adequate method of contraception throughout the study and

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Lithium for treatment of amyotrophic lateral sclerosis: much ado about nothing

Año 2016
Revista Neurologia (Barcelona, Spain)
Enlaces Pubmed , Virtual Health Library , DOI

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Introduction: Lithium was proposed in 2008 as an effective candidate in the treatment of ALS after a report claimed that it was able to delay functional deterioration by 40% and that none of the 16 patients treated with a combination of lithium plus riluzole had died during a 15-month follow-up period. The excellent results of this pilot study engendered considerable optimism among patients, their families, patients’ associations, and the scientific community. This report sparked numerous phase ii clinical trials. Many patients who were not included in these studies used all resources at their disposal to access the drug as treatment under a compassionate use programme. Objectives: To evaluate the effectiveness of lithium in ALS using a meta-analysis of the information reported in 12 studies which were examined for methodological quality. Material and methods: Searches were performed using MEDLINE, EMBASE, the Cochrane Neuromuscular Disease Group Trials Register, ClinicalTrials.gov, and EudraCT (January 1996-August 2012). Results: To date, we have information on more 1100 patients treated with lithium. Unfortunately, the results do not confirm the positive effect described in the pilot study, which suggests that this drug is not effective at slowing disease progression. Two trials had to be suspended before the scheduled completion date due to the ineffectiveness of the drug as well as numerous adverse effects. A recently published study also ruled out any possible modest effect. Conclusions: There is evidence to suggest that lithium has no short-term benefits in ALS. A comparison of the group of patients treated with lithium + riluzole and the control group treated with riluzole alone showed no statistically significant differences in rates of functional decline, deterioration of respiratory function, or survival time. Furthermore, there was no evidence that it was more effective than the placebo

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Drug repurposing: a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis.

Año 2015
Revista PloS one
Enlaces Pubmed , PMC , DOI

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OBJECTIVE:

To develop and implement an evidence based framework to select, from drugs already licenced, candidate oral neuroprotective drugs to be tested in secondary progressive multiple sclerosis.

DESIGN:

Systematic review of clinical studies of oral putative neuroprotective therapies in MS and four other neurodegenerative diseases with shared pathological features, followed by systematic review and meta-analyses of the in vivo experimental data for those interventions. We presented summary data to an international multi-disciplinary committee, which assessed each drug in turn using pre-specified criteria including consideration of mechanism of action.

RESULTS:

We identified a short list of fifty-two candidate interventions. After review of all clinical and pre-clinical evidence we identified ibudilast, riluzole, amiloride, pirfenidone, fluoxetine, oxcarbazepine, and the polyunsaturated fatty-acid class (Linoleic Acid, Lipoic acid; Omega-3 fatty acid, Max EPA oil) as lead candidates for clinical evaluation.

CONCLUSIONS:

We demonstrate a standardised and systematic approach to candidate identification for drug rescue and repurposing trials that can be applied widely to neurodegenerative disorders.

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