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