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

NCT01049399 | Completed DMC

• 1 other identifier: NP031112-08B02
• Study Type: interventional
• Target: 146
• Locations: 4 countries
• Sites: 24

Brief 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

Conditions

Progressive Supranuclear Palsy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Number of AEs and patients with an incidence rate of ≥ 5% AEs

  52 weeks

• Change from Baseline between 2 active study medication groups vs placebo group in Modified Schwab and England Scale

  52 weeks

• Change from Baseline between 2 active study medication groups vs placebo group in Timed Up and Go Test (quantitative motor function)

  52 weeks

• 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

• Change from Baseline between 2 active study medication groups vs placebo group in Starkstein Apathy Scale (behavior)

  52 weeks

Study Arms (3)

Placebo

PLACEBO COMPARATOR

once daily administration of powder for oral suspension.

Drug: placebo

NP031112 800 mg

EXPERIMENTAL

Group dosed with 800 mg once daily for 52 weeks

Drug: tideglusib

NP031112 600 mg

EXPERIMENTAL

Group treated with 600 mg once daily for 52 weeks

Drug: tideglusib

Interventions

tideglusib DRUG

800 mg of tideglusib as a powder for oral suspension once daily in fasting conditions for 52 weeks

Also known as: NP031112

NP031112 800 mg

placebo DRUG

powder for oral suspension administered once daily in fasting conditions for 52 weeks

Placebo

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Age of 40 to 85 years (patients over 85 years could be included after previous assessment by Investigator and approved by sponsor).
• 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.
• Mild-to-moderate stage of disease severity according to score of 1 to 4 in Golbe Staging System.(Appendix 2)
• 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.
• 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.
• Patients living at home or in retirement home not requiring continuous nursing care.
• General health status acceptable for participation in 64-week clinical trial.
• Ability to swallow 100 mL of water suspension.
• 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.
• Occupational, physical, respiratory, or speech therapy is allowed but it must be stable for at least 1 month prior to screening.
• 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.
• Signed informed consent by patient and permitted prior to initiation of any study-specific procedure.

You may not qualify if:

• Failure to perform screening or baseline examinations.
• 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).
• 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.).
• A current Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) diagnosis of active major depression, schizophrenia or bipolar disorder.
• 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)

Sponsors & Collaborators

• Noscira SA: lead
• i3 Research: collaborator

Study Sites (24)

The Parkinson's and Movement Disorder Institute

Fountain Valley, California, 92708, United States

Location

Department of Neurology, David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of South Florida 5

Tampa, Florida, 33606, United States

Location

Division of Movement Disorders, University of Louisville

Louisville, Kentucky, 40202, United States

Location

University of Medicine and Dentistry, Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

Location

Neurologisches Fachkrankenhaus für Bewegungsstörungen/Parkinson Beelitz

Beelitz-Heilstätten, 14547, Germany

Location

Humboldt Universitat Charite, Campus Virchow, Neurologisch

Berlin, 13353, Germany

Location

Universitatsklinikum Carl-Guslav-Carus, Technische Universitat Dresden, Klinik und Poliklinik fur Neurologie

Dresden, 01307, Germany

Location

Medizinische Hochschule Hannover, Neurologie 0E 7210

Hanover, 30625, Germany

Location

Zentrum fur Nervenheilkunde. Klinik fur Neurologie mit Poliklinik.

Marburg, 35039, Germany

Location

University Hospital Tuebingen,Eberhard-Karls-Universitat, Universitatsklinikum Neurologie

Tübingen, 72076, Germany

Location

Fundació Ace

Barcelona, Barcelona, 08014, Spain

Location

Hospital Puerta del Hierro

Madrid, Madrid, 28222, Spain

Location

Hospital de Cruces

Barakaldo, 48902, Spain

Location

Dpto.neurologia. H. Clinic.

Barcelona, 08036, Spain

Location

Hospital de Donostia

Donostia / San Sebastian, 20014, Spain

Location

Dpt. Neurologia. Hospital Ramón y Cajal.

Madrid, 28034, Spain

Location

Hospital U. La Paz

Madrid, 28046, Spain

Location

Hospital Mutua Terrassa

Terrassa, 8221, Spain

Location

Departement of Neurology, Hospital La Fe

Valencia, 460009, Spain

Location

The Walton Centre for Neurology and Neurosurgery NHS Trust

Liverpool, L9 7LJ, United Kingdom

Location

Reta Lila Weston Institute of Neurological Studies,Sara Koe PSP Research Centre

London, WC1N 1PJ, United Kingdom

Location

Clinical Ageing Research Unit

Newcastle upon Tyne, NE4 5PL, United Kingdom

Location

Related Publications (1)

• Hoglinger GU, Schope J, Stamelou M, Kassubek J, Del Ser T, Boxer AL, Wagenpfeil S, Huppertz HJ; AL-108-231 Investigators; Tauros MRI Investigators; Movement Disorder Society-Endorsed PSP Study Group. Longitudinal magnetic resonance imaging in progressive supranuclear palsy: A new combined score for clinical trials. Mov Disord. 2017 Jun;32(6):842-852. doi: 10.1002/mds.26973. Epub 2017 Apr 24.

  PMID: 28436538 DERIVED

MeSH Terms

Conditions

Supranuclear Palsy, Progressive

Interventions

tideglusib

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Tauopathies; Neurodegenerative Diseases; Paralysis; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2010
• First Posted: January 14, 2010
• Study Start: December 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: November 1, 2011
• Last Updated: January 5, 2012

Record last verified: 2012-01

Locations

ES (9); US (6); DE (6); GB (3)