A double-blind, placebo-controlled, randomized, parallel-group study evaluating the safety, tolerability and efficacy of two different oral doses of NP031112, a GSK-3 inhibitor, versus placebo in the treatment of patients with mild to moderate Progressive Supranuclear Palsy. - TAUROS

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2009-013097-40-GB
• Date of registration: 23/07/2009
• Prospective Registration: Yes
• Primary sponsor: Noscira S.A.
• Public title: A double-blind, placebo-controlled, randomized, parallel-group study evaluating the safety, tolerability and efficacy of two different oral doses of NP031112, a GSK-3 inhibitor, versus placebo in the treatment of patients with mild to moderate Progressive Supranuclear Palsy. - TAUROS
• Scientific title: A double-blind, placebo-controlled, randomized, parallel-group study evaluating the safety, tolerability and efficacy of two different oral doses of NP031112, a GSK-3 inhibitor, versus placebo in the treatment of patients with mild to moderate Progressive Supranuclear Palsy. - TAUROS
• Date of first enrolment: 30/10/2009
• Target sample size: 140
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-013097-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Spain, United Kingdom

Key inclusion & exclusion criteria

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 4 weeks 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 4 weeks prior to baseline.

12. Pharmacological treatment of any other chronic condition must be stable and well-tolerated for at least 4 weeks prior to baseline. 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 clinically active hypothyroidism, clinically significant 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

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Mild to Moderate Progressive Supranuclear Palsy
MedDRA version: 12.0 Level: LLT Classification code 10036813 Term: Progressive supranuclear palsy
MedDRA version: 12.0 Level: PT Classification code 10036813 Term: Progressive supranuclear palsy

Intervention(s)

Product Name: NP031112
Product Code: NP031112 600mg
Pharmaceutical Form: Powder for oral suspension
CAS Number: 865854-05-3
Current Sponsor code: NP031112
Other descriptive name: 4-benzyl-2-naphtalen-1-yl-1,2,4-thiadiazolidine-3,5-dione
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 600-
Pharmaceutical form of the placebo: Powder for oral suspension
Route of administration of the placebo: Oral use

Product Name: NP031112
Product Code: NP031112 800mg
Pharmaceutical Form: Powder for oral suspension
CAS Number: 865854-05-3
Current Sponsor code: NP031112
Other descriptive name: 4-benzyl-2-naphtalen-1-yl-1,2,4-thiadiazolidine-3,5-dione
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 800-
Pharmaceutical form of the placebo: Powder for oral suspension
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: 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).

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.

Secondary Objective: 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

Secondary ID(s)

NP031112-08B02

Ethics review

Status: Approved
Approval date:
Contact: