E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Idiopathic Parkinson´s Disease |
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E.1.1.1 | Medical condition in easily understood language |
Idiopathic Parkinson´s Disease |
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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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To establish the combined safety and tolerability profile of oral Fasudil solution over 22 days |
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E.2.2 | Secondary objectives of the trial |
• To establish the tolerability profile of oral Fasudil solution over 22 days • To establish the safety profile of oral Fasudil solution over 22 days and until the end of the follow-up period • To establish symptomatic effects of Fasudil on motor and non-motor symptoms in a dose-response relationship (2 Fasudil doses versus placebo): o Motor function assessed by MDS-UPDRS each part I to IV o Motor function assessed by MDS-UPDRS score part I to IV o Quality of life assessed by PDQ-8 o Non-motor function assessed by NMSQuest o Cognitive function assessed by MoCA o Depressive symptoms assessed by BDI-II o Global clinical impression of change assessed by PGI-I/CGI-I
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with a diagnosis of at least probable PD according to MDS criteria (Postuma et al. MovDis 2015) and 2. Hoehn & Yahr stage 1 – 3 3. must be non-fluctuating (no wearing-off, no dyskinesia) and stable on symptomatic PD medication for at least 6 weeks 4. age: 30 - 80 years 5. Women of childbearing age potential must be non-lactating and surgically sterile or using a highly effective method of birth control and have a negative pregnancy test. Acceptable methods of birth control with a low failure rate (i.e. less than 1% per year) when used consistently and correct are for example implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence or vasectomized partner 6. Capable of thoroughly understanding all information given and giving full informed consent according to GCP
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E.4 | Principal exclusion criteria |
1. Atypical, secondary Parkinsonian syndromes, PD mimics, or any other medical condition known to have an association with Parkinsonian syndromes, which might confound or obscure the diagnosis of PD 2. Patients with a history of intracranial bleeding, known intracerebral aneurysms or Moyamoya disease, or positive family history for the above. If only family history positive, MR- or x-ray-based cranial imaging not older than 24 months must confirm absence of bleeding, aneurysms, or Moyamoya 3. Presence of any concomitant life-threatening disease or impairment likely to interfere with functional assessment 4. Patients with known arterial hypotension (resting blood pressure <90/60 mmHg) or previous hypotensive episodes or requiring treatment for increasing of blood pressure, such as fludrocortisone, midodrine, etilefrine, cafedrine, or theodrenaline 5. Patients with an uncontrollable or unstable arterial hypertensive disease (resting blood pressure >180 mmHg systolic and/or >120 mmHg diastolic under current antihypertensive medication) 6. Known pulmonary hypertension and any medication prescribed for treatment of pulmonary hypertension 7. Confirmed hepatic insufficiency or abnormal liver function (stable ASAT and/or ALAT greater than 3 times the upper limit of the normal range) and determined to be non-transient through repeat testing 8. Renal insufficiency with a glomerular filtration rate (GFR) <60 ml/min/1,73m² (calculated by MDRD equation) or XY (calculated by CKD-EPI equation) and determined to be non-transient through repeat testing 9. Major psychiatric disorder, significant cognitive impairment or clinically evident dementia precluding evaluation of symptoms 10. Hypersensitivity to any component of the IMP 11. Liable to be not cooperative or comply with the trial requirements (as assessed by the investigator), or unable to be reached in the case of emergency 12. Pregnant or breast-feeding females or females with childbearing potential, if no adequate contraceptive measures are used 13. Previous participation in another clinical study involving trial medication within the preceding 12 weeks or five terminal half times of the longest to be eliminated trial medications (whichever is longer) or previous participation in this trial
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E.5 End points |
E.5.1 | Primary end point(s) |
Combined occurrence of intolerance (termination of treatment because of treatment-related AE) and occurrence of self-reported and pre-defined (laboratory, vital signs) treatment-related SAEs [time frame: from day 1 to day 22]. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Occurrence of intolerance (termination of treatment because of treatment-related AE) [time frame: from day 1 to day 22]. • Occurrence of self-reported and pre-defined (laboratory, vital signs) treatment-related SAEs [time frame: from day 1 to day 22, and day 1 to day 50]. • the change of MDS-Unified PD Rating Scale (MDS-UPDRS) each part I to IV [time frame: part I and II from day 1 to day 22, and day 1 to day 50; time frame: part III and IV from day 1 to day 10, day 1 to day 22, and day 1 to day 50] • the change of MDS-Unified PD Rating Scale (MDS-UPDRS) score part I to IV • the change of 8-item PD Quality of Life Scale (PDQ-8) [time frame: from day 1 to day 22, and day 1 to day 50] • the change of PD Non-Motor Symptom Questionnaire (NMSQuest) [time frame: from day 1 to day 10, day 1 to day 22, and day 1 to day 50] • the change of Montreal Cognitive Assessment (MoCA) [time frame: from day 1 to day 22, and day 1 to day 50] • the change of Becks depression inventory-II (BDI-II) [time frame: from day 1 to day 22, and day 1 to day 50], • the Global Impression of Improvement score (CGI-I [clinician], PGI-I [patient]) [time point: at day 10, 22 and day 50].
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Occurrence of intolerance: from day 1 to day 22 • Occurrence of self-reported and pre-defined treatment-related SAEs: from day 1 to day 22, and day 1 to day 50 • the change of MDS-UPDRS each part I to IV: part I and II from day 1 to day 22, and day 1 to day 50; time frame: part III and IV from day 1 to day 10, day 1 to day 22, and day 1 to day 50 • the change of MDS-UPDRS score part I to IV • the change of PDQ-8: from day 1 to day 22, and day 1 to day 50 • the change of NMSQuest: from day 1 to day 10, day 1 to day 22, and day 1 to day 50 • the change of MoCA: from day 1 to day 22, and day 1 to day 50 • the change of BDI-II: from day 1 to day 22, and day 1 to day 50 • CGI-I [clinician], PGI-I [patient]: at day 10, 22 and day 50
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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 | No |
E.6.9 | Dose response | Yes |
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 | 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 | No |
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.8.2.4 | Number of treatment arms in the trial | 3 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 14 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |