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

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