Phase IIa 20 Week Double-blind, Placebo-controlled, Randomized, Escalating Dose Study to Evaluate the Safety and Tolerability of Four Oral Doses of NP031112, a Novel GSK3 Inhibitor, in Mild to Moderate Alzheimer's Disease Patients With Stable Anticholinesterasic Treatment.
Phase IIa 20 Week Double-blind, Placebo-controlled, Randomized, Escalating Dose Study to Evaluate the Safety and Tolerability of Four Oral Doses of NP031112, a Novel GSK3 Inhibitor, in Mild to Moderate Alzheimer's Disease Patients With Stable Anticholinesterasic Treatment.
The purpose of this study is to evaluate if 4 escalating doses during 20 weeks of NP031112 are safe and tolerated in patients with Alzheimer´s disease.
Inclusion Criteria:
Men and women (non-childbearing potential) with a diagnosis of probable Alzheimer's disease according to the NINCDS-ADRDA clinical criteria.
Age 60 - 85 years (patients over 85 years could be included after a previous assessment by the investigator and in agreement with the sponsor)
MRI or CT-scan assessment within 12 months before baseline corroborating the clinical diagnosis (diffuse brain atrophy predominating in medial temporal regions) and excluding other potential causes of dementia, especially cerebrovascular lesions (see exclusion criteria, number 3).
Mild to moderate stage of Alzheimer's disease according to MMSE 16-26.
Modified Hachinski ischemic score equal to or below 4.
Geriatric Depression Scale below or equal 7.
Female patients must be either surgically sterilized or at least 1 year postmenopausal (confirmed by FSH >20, for women not surgically sterilized).
A caregiver/nurse is available and is living in the same household, or interacts with the patient to assure the correct preparation and administration of the study drug to the patient.
Patients living at home or old people's home.
General health status acceptable for a participation in a 6 months clinical trial.
Ability to swallow 100 -150 ml of water suspension.
No daily-regular/chronic intake of medications acting on central nervous system, immunosuppressants, steroids or non-steroid anti-inflammatory agents except the following allowed treatments:
SSRIs as antidepressants if they are administered at a stable and well tolerated dose for two months prior to baseline evaluation
the following drugs at a stable and well tolerated dose to symptomatic treatment of mild behavioral disorder, sleep onset-insomnia or mild depressive mood:
Hydromorphon max 4mg/day
Levodopa max 50mg t.i.d as treatment of an age-associated extrapyramidal syndrome or restless-legs-syndrome
Acetylsalicylic acid max 100mg/day as antiplatelet agent.
Non-steroid anti-rheumatics as concomitant medication taken per request
No history of treatment with Warfarin, Digitoxin or Coumarin (including its derivatives) within 1 month prior to baseline. Chronic treatment with heparin s.c. as anticoagulant or digoxin for the treatment of heart disease are allowed.
Other drugs metabolized by the CYP3A4 with wide therapeutic window are permitted if their dose and regimen are stable and well tolerated for at least 1 month prior to baseline.
Stable pharmacological treatment of any other chronic condition for at least one month prior to screening.
Treatment with a stable and well tolerated dose of one of the approved Acetylcholinesterase-Inhibitors (Donepezil, Galantamine or Rivastigmine) for at least 2 months prior to baseline evaluations. Dosage of Acetylcholine-esterase inhibitors should not be increased during the ongoing study.
No history of treatment with Memantine within 3 months prior to baseline evaluation. Patients with a stable and well tolerated dose of Memantine are not allowed to be included in the study.
Signed informed consent by patient prior to the initiation of any study specific procedure
Exclusion Criteria:
Failure to perform screening or baseline examinations.
Hospitalization or change of chronic concomitant medication within 1 month prior to screening period.
Clinical, laboratory or neuroimaging findings consistent with:
A current DSM-IV diagnosis of active major depression, schizophrenia or bipolar disorder.
Clinically significant, advanced or unstable disease that may interfere with evaluations that may bias the assessment of the clinical or mental status of the patient or put the patient at special risk, such as:
Disability that may prevent the subject from completing all study requirements (e.g., blindness, deafness, severe language difficulty, etc.)
Women who are fertile and of child bearing potential.
Anticoagulant treatment with heparin i.v.
Chronic drug intake of:
Suspected or known drug or alcohol abuse.
Suspected or known allergy to any components of the study treatments.
Enrolment in another investigational study or intake of investigational drug within the previous 3 months.
Any condition which in the opinion of the investigator makes the patient unsuitable for inclusion.