E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Amyotrophic Lateral Sclerosis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002026 |
E.1.2 | Term | Amyotrophic lateral sclerosis |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal 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 See section 11.2.1.1 for details 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 8805; 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 for 2 weeks after post study visit. Adequate methods of contraception for themselves or their partner include but are not limited to barrier method i.e. condoms, diaphragm with spermicide gel , surgical sterilisation, vasectomy and abstinence 8. Able and willing to give written informed consent, personally or via their legally authorised representative See 7.2.2. |
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E.4 | Principal exclusion criteria |
1. Presence of a tracheotomy, mechanical ventilation or non-invasive ventilation as evidenced by a score of 8804; 3 on ALSFRS-R question i respiratory insufficiency at Visit 1 screening visit 2. Requirement for prescription drugs used for potential neuroprotective benefit listed in section 10.5.3.1, for one month prior to Visit 1 screening visit 3. Requirement for prescription drugs that are metabolised via the cytochrome P450 2C9 listed in section 10.5.3.2, for one week prior to Visit 1 screening visit 4. A clinically relevant medical history or presence of respiratory diseases or disorders such as moderate-to-severe asthma and chronic obstructive pulmonary disease that, in the opinion of the Investigator, may pose an unwarranted risk to the subject or confound the results of the study 5. A history or presence of malignancy within the past 3 years 6. A history or presence of other life threatening diseases within the past 3 years 7. A clinically relevant medical history or presence of cardiovascular, gastrointestinal, renal, hepatic, endocrine/metabolic, neurologic, lymphatic, haematologic, immunologic, musculoskeletal, connective tissue, dermatologic, genito/urinary, psychiatric diseases or disorders that, in the opinion of the investigator, may pose an unwarranted risk to the subject or confound the results of the study 8. Presence or intention of pregnancy and breast feeding female subjects only 9. Males with the intention of fathering a child during the study period 10. A history of drug or alcohol abuse alcoholic subjects who are recovered for at least 2 years will be allowed to enrol in the study 11. Subjects who have used any investigational drug and /or participated in any clinical trial within 3 months of entry to this study 12. Subjects who have previously received ONO-2506PO |
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E.5 End points |
E.5.1 | Primary end point(s) |
Slope of respiratory function, SVC expressed as a percentage of the predicted value, over the treatment period. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Inclusione soggetti bulbari e non bulbari |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |