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

NCT ID: NCT01049399

Last Updated: 2012-01-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 146 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2011-11-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

once daily administration of powder for oral suspension.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

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

NP031112 800 mg

Group dosed with 800 mg once daily for 52 weeks

Group Type: EXPERIMENTAL

tideglusib

Intervention Type: DRUG

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

NP031112 600 mg

Group treated with 600 mg once daily for 52 weeks

Group Type: EXPERIMENTAL

tideglusib

Intervention Type: DRUG

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

Interventions

tideglusib

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

Intervention Type: DRUG

tideglusib

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

Intervention Type: DRUG

placebo

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

Intervention Type: DRUG

Other Intervention Names

NP031112; NP031112

Eligibility 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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

i3 Research

INDUSTRY

Sponsor Role: collaborator

Noscira SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Parkinson's and Movement Disorder Institute

Fountain Valley, California, United States

Department of Neurology, David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

University of South Florida 5

Tampa, Florida, 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

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

Hanover, , Germany

Zentrum fur Nervenheilkunde. Klinik fur Neurologie mit Poliklinik.

Marburg, , Germany

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

Tübingen, , Germany

Fundació Ace

Barcelona, Barcelona, Spain

Hospital Puerta del Hierro

Madrid, Madrid, Spain

Hospital de Cruces

Barakaldo, , Spain

Dpto.neurologia. H. Clinic.

Barcelona, , Spain

Hospital de Donostia

Donostia / San Sebastian, , Spain

Dpt. Neurologia. Hospital Ramón y Cajal.

Madrid, , Spain

Hospital U. La Paz

Madrid, , Spain

Hospital Mutua Terrassa

Terrassa, , Spain

Departement of Neurology, Hospital La Fe

Valencia, , Spain

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 Kingdom

Countries

United States; Germany; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 28436538 (View on PubMed)

Other Identifiers

NP031112-08B02

Identifier Type: -

Identifier Source: org_study_id