E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Progressive neurodegenerative disease of the nervous system that affects movement. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061536 |
E.1.2 | Term | Parkinson's disease |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061536 |
E.1.2 | Term | Parkinson's disease |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effects of the study drug EPI-589 on safety as assessed by occurrence of drug-related adverse events in subjects with Parkinson's disease. |
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E.2.2 | Secondary objectives of the trial |
Secondary research objectives for this study are to evaluate whether the study drug, EPI-589, affects the following in subjects with Parkinson's disease: 1. Markers of energy production and protection from oxidative stress in nerve cells (fasting glutathione cycle biomarkers) as measured in blood, cerebral spinal fluid (CSF - the fluid that surrounds the brain and spinal cord), and urine. A biomarker is something we can measure that helps us to better understand a disease. Glutathione is an important antioxidant, which prevents damage to important cellular components caused by the accumulation of “bad” molecules called free radicals. Free radical damage within cells has been linked to a range of disorders including cancer, arthritis, atherosclerosis, Alzheimer's disease, Parkinson’s disease and diabetes. Glutathione levels are directly related to disease severity in patients with Parkinson's disease. Biomarkers in blood will be measured at run-in, baseline, month 1 and month 3 timepoin |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Hoehn and Yahr stage ≤ 3.0 2. Ambulatory with or without assistance 3. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., hormonal methods, including oral, subcutaneous, and intrauterine; barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 3 months after the last dose of study treatment. 4. Willingness and ability to comply with study procedures 5. If on medications and supplements for Parkinson's disease, then regimen must be stable for 60 days prior to enrollment 6. Abstention from use of other investigative or non-approved drugs for the duration of the trial 7. For idiopathic subjects: a diagnosis of idiopathic Parkinson's disease confirmed by the presence of bradykinesia plus one or both of the following symptoms: rigidity or resting tremor; and with an abnormal DaTscan consistent with a dopaminergic deficit 8. For idiopathic subjects: age 40 to 75 years 9. For idiopathic subjects: within 5 years of diagnosis of Parkinson’s disease 10. For genetic subtype subjects: a confirmed diagnosis of Parkinson's disease plus a genetic diagnosis consistent with Parkinson's disease, specifically PINK1, parkin, LRRK2 or other mitochondrial genetic subtype 11. For genetic subtype subjects: age 21 to 75 years |
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E.4 | Principal exclusion criteria |
1. Allergy to EPI-589 or other components of the EPI-589 tablet formulation 2. Vitamins E and C beyond the recommended daily allowance. 3. Other Parkinsonian disorders 4. MoCA score of < 24 5. Revised Hamilton Rating Scale for Depression ≥ 11 6. Parkinsonism due to drugs or toxins 7. Diagnosis of any other clinically significant neurologic disease that will confound the assessment of effect of study drug on disease progression 8. Malignancy within past two years 9. Pregnant or plans to become pregnant or breast feeding 10. History of stroke 11. History of brain surgery 12. Hepatic insufficiency with liver function tests (LFTs) > 3 times upper limit of normal 13. Renal insufficiency as defined by creatinine > 1.5 times normal 14. End stage cardiac failure 15. Participation within past 3 months and for duration of study in a trial of a device, drug or other therapy for Parkinson's disease
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety as assessed by occurrence of drug-related adverse events in subjects with Parkinson's disease. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening (-2 to -1 months), Run-in (-2 to -1 months), Baseline, Month 1, Month 2, and Month 3 |
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E.5.2 | Secondary end point(s) |
EFFICACY 1. Fasting blood-based biomarkers 2. Fasting CNS-based biomarkers 3. Fasting urine-based biomarkers 4. MDS-UPDRS 5. NMSS 6. PDQ-39 7. EQ-5D 8. MoCA 9. BDI 10. MADRS 11. Timed motor tests in ON state only (for subjects on dopamine therapy) 12. Pharmacokinetics
SAFETY 13. Routine assessments of AEs and SAEs 14. Dose limiting toxicities 15. Routine serum chemistries with liver function tests 16. Routine hematology tests with coagulation tests 17. Electrocardiogram 18. C-SSRS |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Run-in (-2 to -1 months), Baseline, Month 1, and Month 3 2. Run-in (-2 to -1 months) and Month 3 3. Run-in (-2 to -1 months), Baseline, Month 1, and Month 3 4. Screening (-2 to -1 months), Baseline, Month 1, and Month 3 5. Baseline and Month 3 6. Baseline and Month 3 7. Baseline and Month 3 8. Screening (-2 to -1 months) and Month 3 9. Baseline and Month 3 10. Baseline and Month 3 11. Run-in (-2 to -1 months), Baseline, and Month 3 12. Month 1 and Month 3 13. Screening (-2 to -1 months), Run-in (-2 to -1 months), Baseline, Month 1, Month 2, and Month 3 14. Monitored throughout study 15. Screening (-2 to -1 months), Baseline, Month 1, and Month 3 16. Screening (-2 to -1 months), Baseline, Month 1, and Month 3 17. Screening (-2 to -1 months), Baseline, Month 1, an |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Within-subject, controlled, open-label study |
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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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Natural history of disease |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 10 |
E.8.9.1 | In the Member State concerned days | 30 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 30 |