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 (Tauros)

This study has been completed.
Sponsor:
Collaborator:
i3 Research
Information provided by (Responsible Party):
Noscira SA
ClinicalTrials.gov Identifier:
NCT01049399
First received: January 13, 2010
Last updated: January 2, 2012
Last verified: January 2012
  Purpose

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


Condition Intervention
Progressive Supranuclear Palsy
Drug: tideglusib
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Noscira SA:

Primary Outcome Measures:
  • 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 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of AEs and patients with an incidence rate of ≥ 5% AEs [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  • Change from Baseline between 2 active study medication groups vs placebo group in Modified Schwab and England Scale [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline between 2 active study medication groups vs placebo group in Timed Up and Go Test (quantitative motor function) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline between 2 active study medication groups vs placebo group in Starkstein Apathy Scale (behavior) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline between 2 active study medication groups vs placebo group in Clinical Global Impression of Change [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline between 2 active study medication groups vs placebo group in Clinical Global Impression of Severity [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Enrollment: 146
Study Start Date: December 2009
Study Completion Date: November 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
once daily administration of powder for oral suspension.
Drug: placebo
powder for oral suspension administered once daily in fasting conditions for 52 weeks
Experimental: NP031112 800 mg
Group dosed with 800 mg once daily for 52 weeks
Drug: tideglusib
800 mg of tideglusib as a powder for oral suspension once daily in fasting conditions for 52 weeks
Other Name: NP031112
Experimental: NP031112 600 mg
Group treated with 600 mg once daily for 52 weeks
Drug: tideglusib
600 mg of tideglusib as a powder for oral suspension, administered once daily in fasting conditions for 52 weeks
Other Name: NP031112

  Eligibility

Ages Eligible for Study:   40 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01049399

Locations
United States, California
The Parkinson's and Movement Disorder Institute
Fountain Valley, California, United States, 92708
Department of Neurology, David Geffen School of Medicine at UCLA
Los Angeles, California, United States, 90095
United States, Florida
Mayo Clinic Jacksonville
Jacksonville, Florida, United States, 32224
University of South Florida 5
Tampa, Florida, United States, 33606
United States, Kentucky
Division of Movement Disorders, University of Louisville
Louisville, Kentucky, United States, 40202
United States, New Jersey
University of Medicine and Dentistry, Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08901
Germany
Neurologisches Fachkrankenhaus für Bewegungsstörungen/Parkinson Beelitz
Beelitz-Heilstätten, Germany, 14547
Humboldt Universitat Charite, Campus Virchow, Neurologisch
Berlin, Germany, 13353
Universitatsklinikum Carl-Guslav-Carus, Technische Universitat Dresden, Klinik und Poliklinik fur Neurologie
Dresden, Germany, 01307
Medizinische Hochschule Hannover, Neurologie 0E 7210
Hannover, Germany, 30625
Zentrum fur Nervenheilkunde. Klinik fur Neurologie mit Poliklinik.
Marburg, Germany, 35039
University Hospital Tuebingen,Eberhard-Karls-Universitat, Universitatsklinikum Neurologie
Tubingen, Germany, 72076
Spain
Hospital de Cruces
Barakaldo, Spain, 48902
Dpto.neurologia. H. Clinic.
Barcelona, Spain, 08036
Fundació Ace
Barcelona, Spain, 08014
Hospital U. La Paz
Madrid, Spain, 28046
Hospital Puerta del Hierro
Madrid, Spain, 28222
Dpt. Neurologia. Hospital Ramón y Cajal.
Madrid, Spain, 28034
Hospital de Donostia
San Sebastian, Spain, 20014
Hospital Mutua Terrassa
Terrasa, Spain, 8221
Departement of Neurology, Hospital La Fe
Valencia, Spain, 460009
United Kingdom
The Walton Centre for Neurology and Neurosurgery NHS Trust
Liverpool, United Kingdom, L9 7LJ
Reta Lila Weston Institute of Neurological Studies,Sara Koe PSP Research Centre
London, United Kingdom, WC1N 1PJ
Clinical Ageing Research Unit
Newcastle upon Tyne, United Kingdom, NE4 5PL
Sponsors and Collaborators
Noscira SA
i3 Research
  More Information

No publications provided

Responsible Party: Noscira SA
ClinicalTrials.gov Identifier: NCT01049399     History of Changes
Other Study ID Numbers: NP031112-08B02
Study First Received: January 13, 2010
Last Updated: January 2, 2012
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Spain: Spanish Agency of Medicines
Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Supranuclear Palsy, Progressive
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Cranial Nerve Diseases
Eye Diseases
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Neurologic Manifestations
Ocular Motility Disorders
Ophthalmoplegia
Paralysis
Signs and Symptoms
Tauopathies

ClinicalTrials.gov processed this record on October 29, 2014