Safety, Tolerability, and Efficacy of Two Different Oral Doses of NP031112 Versus Placebo in the Treatment of Patients With Mild-to-Moderate Progressive Supranuclear Palsy

Progressive Supranuclear Palsy Clinical Trial

— Tauros  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01049399
• Other study ID #: NP031112-08B02
• Status: Completed
• Phase: N/A
• First received: January 13, 2010
• Last updated: January 2, 2012
• Start date: December 2009
• Est. completion date: November 2011

Study information

• Verified date: January 2012
• Source: Noscira SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine wether NP031112 is safe and effective in the treatment of mild to moderate Progressive Supranuclear Palsy

Recruitment information / eligibility

• Status: Completed
• Enrollment: 146
• Est. completion date: November 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Men and women with diagnosis of possible or probable PSP according to clinical criteria of 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 previous assessment by Investigator and approved by sponsor).

3. Brain magnetic resonance imaging (MRI) study within 24 months before 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 score of 1 to 4 in Golbe Staging System.(Appendix 2)

5. Female patients must be surgically sterilized; at least 1 year postmenopausal (confirmed by follicle-stimulating hormone [FSH] >20 international units [IUs]); using adequate birth control (implants, injectables, combined oral contraceptives, intrauterine contraceptive device, total sexual abstinence during the study or vasectomised partner). Male patients must be willing to use barrier contraception (condom) during the study and for 6 months after last treatment administration.

In European arms of study female patients must be without childbearing potential.

6. Caregiver (or dedicated nurse) living in same household or interacting with patient for >4 hours every day able to assure correct preparation and administration of study drug.

7. Patients living at home or in retirement home not requiring continuous nursing care.

8. General health status acceptable for participation in 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 Baseline visit and its dose and regimen should be maintained during 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 by patient and permitted prior to initiation of any study-specific procedure.

Exclusion Criteria:

1. Failure to perform screening or baseline examinations.

2. Hospitalization or change of chronic concomitant medication 1 month prior to or during screening period (apart from pre-planned hospitalization for a condition, which did not deteriorate since 1 month prior to 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 Guadeloupe; Alzheimer's disease; amyotrophic lateral sclerosis; Creutzfeldt-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 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 clinical or mental assessment or put 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 manifestations of liver disease

• respiratory insufficiency

• renal insufficiency (serum creatinine >2 mg/dL (>150 micromol/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 2 months prior to 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 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 cytochrome P450 (CYP)3A4 with narrow therapeutic window (acenocoumarol, warfarin, and digitoxin)

• anticonvulsants indicated for epileptic seizures

• systemic anticholinergics with relevant action on central nervous system

• 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 such as clonidine, alpha 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 study treatments.

10. Enrollment in another investigational drug study within 3 months before Baseline visit.

11. Any condition, which in the opinion of Investigator makes patient unsuitable for inclusion or likely to be non-compliant.

• More than 21 units per week for men and 14 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 spirit.

Related Conditions & MeSH terms

• Paralysis
• Progressive Supranuclear Palsy
• Supranuclear Palsy, Progressive

Intervention

Drug:
• tideglusib
800 mg of tideglusib as a powder for oral suspension once daily in fasting conditions for 52 weeks
• tideglusib
600 mg of tideglusib as a powder for oral suspension, administered once daily in fasting conditions for 52 weeks
• placebo
powder for oral suspension administered once daily in fasting conditions for 52 weeks

Locations

Country	Name	City	State
Germany	Neurologisches Fachkrankenhaus für Bewegungsstörungen/Parkinson Beelitz	Beelitz-Heilstätten
Germany	Humboldt Universitat Charite, Campus Virchow, Neurologisch	Berlin
Germany	Universitatsklinikum Carl-Guslav-Carus, Technische Universitat Dresden, Klinik und Poliklinik fur Neurologie	Dresden
Germany	Medizinische Hochschule Hannover, Neurologie 0E 7210	Hannover
Germany	Zentrum fur Nervenheilkunde. Klinik fur Neurologie mit Poliklinik.	Marburg
Germany	University Hospital Tuebingen,Eberhard-Karls-Universitat, Universitatsklinikum Neurologie	Tubingen
Spain	Hospital de Cruces	Barakaldo
Spain	Dpto.neurologia. H. Clinic.	Barcelona
Spain	Fundació Ace	Barcelona
Spain	Dpt. Neurologia. Hospital Ramón y Cajal.	Madrid
Spain	Hospital Puerta del Hierro	Madrid
Spain	Hospital U. La Paz	Madrid
Spain	Hospital de Donostia	San Sebastian
Spain	Hospital Mutua Terrassa	Terrasa
Spain	Departement of Neurology, Hospital La Fe	Valencia
United Kingdom	The Walton Centre for Neurology and Neurosurgery NHS Trust	Liverpool
United Kingdom	Reta Lila Weston Institute of Neurological Studies,Sara Koe PSP Research Centre	London
United Kingdom	Clinical Ageing Research Unit	Newcastle upon Tyne
United States	The Parkinson's and Movement Disorder Institute	Fountain Valley	California
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	Department of Neurology, David Geffen School of Medicine at UCLA	Los Angeles	California
United States	Division of Movement Disorders, University of Louisville	Louisville	Kentucky
United States	University of Medicine and Dentistry, Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	University of South Florida 5	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Noscira SA	i3 Research

Countries where clinical trial is conducted

United States,  Germany,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		52 weeks
Secondary	Number of AEs and patients with an incidence rate of = 5% AEs		52 weeks
Secondary	Change from Baseline between 2 active study medication groups vs placebo group in Modified Schwab and England Scale		52 weeks
Secondary	Change from Baseline between 2 active study medication groups vs placebo group in Timed Up and Go Test (quantitative motor function)		52 weeks
Secondary	Change from Baseline between 2 active study medication groups vs placebo group in cognitive function(Dementia Rating Scale-2,Frontal Assessment Battery,category and letter verbal fluency)		52 weeks
Secondary	Change from Baseline between 2 active study medication groups vs placebo group in Starkstein Apathy Scale (behavior)		52 weeks
Secondary	Change from Baseline between 2 active study medication groups vs placebo group in functional assessments(Unified Parkinson Disease rating Scale part II and European Quality of Life questionnaire)		52 weeks
Secondary	Change from Baseline between 2 active study medication groups vs placebo group in Clinical Global Impression of Change		52 weeks
Secondary	Change from Baseline between 2 active study medication groups vs placebo group in Clinical Global Impression of Severity		52 weeks