E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild to Moderate Progressive Supranuclear Palsy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036813 |
E.1.2 | Term | Progressive supranuclear palsy |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036813 |
E.1.2 | Term | Progressive supranuclear palsy |
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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 |
To evaluate the overall clinical change assessed by the Progressive Supranuclear Palsy Rating Scale of Golbe after 52 weeks of treatment with 2 different doses of NP031112 vs. placebo in patients with possible or probable mild-to-moderate Progressive Supranuclear Palsy (PSP). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of 2 different doses of NP031112 administered over 52 weeks in patients with possible or probable mild to moderate PSP. To evaluate the clinical functional changes after 52 weeks of treatment with 2 different doses of NP031112 vs. placebo on: o motor function o cognition o behavior o activities of daily living (ADL) o quality of life
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men and women with a diagnosis of possible or probable PSP according to the clinical criteria of the National Institute of Neurologic Diseases and Stroke – the Society for PSP (Appendix 1)
2. Age of 40 to 85 years (patients over 85 years could be included after a previous assessment by the Investigator and approved by the sponsor).
3. Brain MRI study within 24 months before the Baseline visit excluding other potential causes of parkinsonism, especially cerebrovascular lesions and space occupying lesions.
4. Mild to moderate stage of disease severity according to a score of 1 to 4 in the Golbe Staging System (Appendix 2).
5. Female patients must be without childbearing potential: either surgically sterilized or at least 1 year postmenopausal (confirmed by follicle-stimulating hormone [FSH] >20 international units [IUs]). Male patients must be willing to use barrier contraception (condom) during the study and for 6 months after the last treatment administration.
6. A caregiver (or dedicated nurse) living in the same household or interacting with the patient for >4 hours every day able to assure the correct preparation and administration of the study drug.
7. Patients living at home or in a retirement home not requiring continuous nursing care.
8. General health status acceptable for a participation in a 64-week clinical trial.
9. Ability to swallow 100 mL of water suspension.
10. Any concomitant medication for PSP must be well-tolerated and unchanged for at least 1 month prior to the Baseline visit and its dose and regimen should be maintained during the study if there are no clinical reasons to modify it.
11. Occupational, physical, respiratory, or speech therapy is allowed but it must be stable for at least 1 month prior to screening.
12. Pharmacological treatment of any other chronic condition must be stable and well-tolerated for at least 1 month prior to screening. Analgesics, occasional per request nonsteroidal anti-inflammatory agents, and treatments for transient or emergent conditions are allowed.
13. Signed informed consent (IC) by the patient (or his/her legal representative, this is applicable in Spain) prior to the initiation of any study-specific procedure.
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E.4 | Principal exclusion criteria |
1. Failure to perform screening or baseline examinations.
2. Hospitalization or change of chronic concomitant medication 1 month prior to or during the screening period (apart from pre-planned hospitalization for a condition, which did not deteriorate since 1 month prior to the screening period).
3. Clinical, laboratory or neuroimaging findings consistent with: • other primary degenerative diseases such as Parkinson’s disease; dementia with Lewy bodies; corticobasal degeneration; frontotemporal dementia; multiple system atrophy; parkinsonism-dementia complex of Guam, Kii or Guadalupe; Alzheimer’s disease; amyotrophic lateral sclerosis; Creutzfeld-Jakob Disease; Huntington’s disease; Down’s syndrome; etc. • cerebrovascular disease as major, strategic or multilacunar infarcts, or extensive white matter lesions scoring 3 in the Wahlund’s scale [Wahlund et al., 2001]. • other central nervous system diseases (hydrocephalus, severe head trauma, tumours, subdural haematoma or other relevant space occupying processes, etc.). • epilepsy. • other infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, present hypothyroidism, present vitamin B12 or folate deficiency, clinically significant serum electrolyte disturbances, juvenile onset diabetes mellitus, etc.).
4. A current Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) diagnosis of active major depression, schizophrenia or bipolar disorder.
5. Clinically significant, advanced or unstable disease that may interfere with primary or secondary variable evaluations, may bias the clinical or mental assessment or put the patient at special risk, such as: • chronic liver disease, as indicated by liver function test abnormalities (ALAT, ASAT, bilirubin or GGT out of range) positive serology for Hepatitis C, or other clinical manifestations of liver disease • respiratory insufficiency • renal insufficiency (serum creatinine >2 mg/dL (>150 μmol/L) and creatinine clearance <60 (according to Cockcroft-Gault formula) • heart disease (myocardial infarction, unstable angina, heart failure, cardiomyopathy within 6 months before screening). • bradycardia (heart beat <50/min) or tachycardia (heart beat >95/min) • episodes of unstable or uncontrolled hypertension (systolic pressure >160 mm Hg or diastolic pressure >100 mm Hg) or hypotension (systolic pressure <90 mm Hg or diastolic pressure <45 mm Hg) during the 2 months prior to the Baseline visit. • atrioventricular block (type II / Mobitz II and type III), congenital long QT syndrome, sinus node dysfunction or prolonged QTcF interval (males >450 msec and females >470 msec using Fridericia’s formula: QTc = QT/cube root of RR). • uncontrolled diabetes mellitus. • malignant tumors within the last 5 years except skin malignancies (other than melanoma) or indolent prostate cancer. • metastases.
6. Disability that may prevent the patient from completing all study requirements (e.g. blindness, deafness, and severe language difficulty).
7. Chronic daily drug intake of: • drugs metabolized by the cytochrome P450 (CYP)3A4 with narrow therapeutic window (acenocoumarol, warfarin, and digitoxin) • antiepileptics • anticholinergics • acetylcholinesterase inhibitors • neuroleptics except quetiapine, clozapine or other atypical neuroleptics • nootropics such as piracetam, propentofylline, hydergine, vinpocetine, ginkgo biloba, coenzyme Q-10, idebenone and derivatives • centrally active anti-hypertensive drugs (clonidine, α-methyl dopa, guanidine, and guanfacine) • systemic cortico-steroids or immunosuppressants • systemic nonsteroidal anti-inflammatory agents (except taken as occasional medication per request or acetylsalicylic acid up to 100 mg/day as an antiplatelet agent). • memantine, lithium, valproic acid or other GSK-3 inhibitors within 3 months prior to the Baseline visit.
8. Suspected or known history of drug abuse or excessive alcohol intake*
9. Suspected or known allergy to any components of the study treatments.
10. Enrollment in another investigational drug study within 3 months before the Baseline visit.
11. Any condition, which in the opinion of the Investigator, makes the patient unsuitable for inclusion or likely to be non-compliant.
* More than 21 units per week for men and more than 14 units a week for women; or consumption of more than 8 units in a single episode. 1 unit equals approximately 1 glass of wine, 250 ml of beer or 1 shot (25 ml) of a spirit |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Endpoint: The change from Baseline between the 2 active study medication groups compared with the placebo group in the Progressive Supranuclear Palsy Rating Scale of Golbe.
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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.8.3 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 | Information not present in EudraCT |
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 | 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 | 0 |
E.8.9.1 | In the Member State concerned months | 20 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 20 |
E.8.9.2 | In all countries concerned by the trial days | 0 |