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

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Brief Title

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

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

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
    



Study Type

Interventional


Primary Outcome

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 Outcome

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

Condition

Progressive Supranuclear Palsy

Intervention

tideglusib

Study Arms / Comparison Groups

 Placebo
Description:  once daily administration of powder for oral suspension.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

146

Start Date

December 2009

Completion Date

November 2011

Primary Completion Date

September 2011

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.
      

Gender

All

Ages

40 Years - 85 Years

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

Germany

Location Countries

Germany

Administrative Informations


NCT ID

NCT01049399

Organization ID

NP031112-08B02


Responsible Party

Sponsor

Study Sponsor

Noscira SA

Collaborators

 i3 Research

Study Sponsor

, , 


Verification Date

January 2012