Safety and Efficacy Study of Ladostigil in Mild to Moderate Probable Alzheimer's Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Avraham Pharmaceuticals Ltd
ClinicalTrials.gov Identifier:
NCT01354691
First received: May 1, 2011
Last updated: July 22, 2013
Last verified: July 2013
  Purpose

For many, Alzheimer's disease is the number one medical issue facing our aging society. It is a late onset neurodegenerative disease, frequently under diagnosed, that impairs memory and cognitive performance. There are no known treatments that can either prevent or reverse its progression. Consequently, there still remains a need to evaluate treatments which can better stabilize the symptoms of this disease. These symptoms frequently include decreased functional capacity and negative psychological attributes (e,g, depression, anxiety) in association with the memory and cognition deficits. This current study is being done to assess an investigational compound that has been designed to not only improved the cognitive status of affected patients but to also better manage all symptoms. Hence, the ultimate goal is to provide patients with an improved quality of life by slowing the progression of this neurodegenerative disease


Condition Intervention Phase
Alzheimer's Disease
Dementia
Memory Loss
Cognitive Impairment
Drug: ladostigil hemitartrate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 6-Month Prospective, Multi-Center, Double-Blind, Placebo-Controlled, Randomized, Adaptive-Trial-Design Study to Evaluate the Safety and Efficacy of 80mg b.i.d Ladostigil in Patients With Mild to Moderate Probable Alzheimer's Disease With a 6-Month Open Label Follow-Up Period

Resource links provided by NLM:


Further study details as provided by Avraham Pharmaceuticals Ltd:

Primary Outcome Measures:
  • ADAS-Cog: Alzheimer's Disease Assessment Scale-Cognitive Subscale [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    11 item, unmodified ADAS-Cog (total possible score of 70)

  • Safety Evaluation [ Time Frame: 6,15 26, 39 and 52 week assessment of safety and tolerability ] [ Designated as safety issue: Yes ]
    Number and severity of adverse events across trial period.


Secondary Outcome Measures:
  • Neuropsychiatric Inventory (NPI) [ Time Frame: 6, 15, 26, 39 and 52 weeks ] [ Designated as safety issue: No ]
    Assessment of behavioral and psychological symptoms of disease

  • Cornell Scale for Depression in Dementia (CSDD) [ Time Frame: 6, 15, 26, 39 and 52 weeks ] [ Designated as safety issue: No ]
    Assessment of depressive status

  • Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) [ Time Frame: 6, 15, 26, 39 and 52 weeks ] [ Designated as safety issue: No ]
    Assessment of functional activity status

  • Mini-Mental State Examination (MMSE) [ Time Frame: 6, 15, 26, 39 and 52 weeks ] [ Designated as safety issue: No ]
    Secondary assessment of cognitive status utilizing common metric

  • ADAS-Cog: Alzheimer's Disease Assessment Scale - Cognitive Subscale [ Time Frame: 6, 15, 39 and 52 weeks ] [ Designated as safety issue: No ]
    11 item, unmodified ADAS-Cog (total possible score of 70)


Enrollment: 201
Study Start Date: February 2011
Study Completion Date: March 2013
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ladostigil hemitartrate Drug: ladostigil hemitartrate
Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.

Detailed Description:

This is a phase II, proof of concept study to evaluate the safety and efficacy of the investigational compound ladostigil versus placebo in mild to moderate Alzheimer's disease patients. The randomized, double-blind, placebo-controlled phase of the trial will be 26 weeks in duration and will involve two cohorts (i.e. one arm receiving ladostigil and one arm receiving placebo). After the initial 26 week period, all participating subjects will receive 26 weeks of treatment with ladostigil (i.e. the open label phase). A total of five territories will be participating in this trial. These include Austria, Croatia, Germany, Serbia and Spain.

  Eligibility

Ages Eligible for Study:   60 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • AD diagnosis according to NINCDS-ADRDA criteria
  • Mild to moderate AD according to MMSE 14-24 inclusive
  • MRI or CT assessment within 6 months before baseline, corroborating the clinical diagnosis and excluding other potential causes of dementia especially cerebrovascular lesions
  • Absence of major depressive disease according to CSDD of less than or equal to 18
  • Modified Hachinski Ischemic Scale equal to or below 4
  • Education for eight or more years
  • Previous decline in cognition for more than six months as documented in patient medical records
  • A caregiver available and living in the same household or interacting with the patient daily and available if necessary to assure administration of investigational product
  • Patients living at home or nursing home setting without continuous nursing care
  • General health status acceptable for participation in a 12-month clinical trial and ability to swallow oral medication
  • No history of treatment with rivastigmine
  • For patients with either donepezil or galantamine anti-cholinesterase inhibitor treatment prescribed, stopped treatment four weeks prior to screening
  • For patients with memantine treatment prescribed, stopped treatment four weeks prior to screening

Exclusion Criteria:

  • Other primary degenerative dementias (e.g. dementia with Lewy bodies, fronto-temporal dementia, Huntington's disease, Jacob-Creutzfeldt disease)
  • Other neurodegenerative conditions (Parkinson's disease. amyotrophic lateral sclerosis, etc)
  • Other central nervous system diseases (severe head trauma, tumors, subdural hematoma, etc)
  • A current DSM-IV diagnosis of active major depression, schizophrenia or bipolar disorder
  • Seizure disorders
  • Other infectious, metabolic or systemic diseases affecting central nervous system (syphilis, present hypothyroidism, present vitamin B12 or folate deficiency, serum electrolytes out of normal range, juvenile onset diabetes mellitus, etc)
  • Clinically significant, advanced or unstable disease that may interfere with primary or secondary variable evaluations
  • Other unstable, chronic or clinically significant medical conditions involving major organs like kidney, liver, lungs and heart/vasculature
  • Hospitalization or change of chronic concomitant medications one month prior to screening or during screening period
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01354691

Locations
Austria
Medizinische Univeritat Graz, Universitatsklinik fur Neurologie, Auenbruggerplatz 22
Graz, Austria, 8036
Privatordination Horn, HamerlingstraBe 15
Horn, Austria, 3580
Allgemeines Krankenhaus der Stadt Linz, KrankenhausstraBe 9
Linz, Austria, 4020
Privatordination, Lainzerstrasse 20
Wein, Austria, 1130
Croatia
General Hospital Pula, Negrijeva 6
Pula, Croatia, 52100
General Hospital Zabok, Bracak 8
Zabok, Croatia, 49210
Clinical Hospital Dubrava, Avenija Gojka Suska 6
Zagreb, Croatia, 10000
Clinical Hospital Center Zagreb, Kispaticeva 12
Zagreb, Croatia, 10000
Psychiatric Hospital Vrapce, Bolnicka cesta 32
Zagreb, Croatia, 10090
Polyclinic Neuron, Salata 12
Zagreb, Croatia, 10000
Germany
Klinische Forschung Hamburg GmbH, Hoheluftaussee 18
Hanburg, Germany, 20253
Klinische Forschung Schwerin GmbH, FriedrichstraBe 1
Schwerin, Germany, 19055
Studienzentrum Nordwest, Lange StraBe 23-25
Westerstede, Germany, 26655
Serbia
Clinical Centre of Serbia, Dr. Subotica 6
Beograd, Serbia, 11000
Military Medical Academy, Crnotravska 17
Beograd, Serbia, 11000
Spain
CAE Oroitu Centro Atencion Especializada C/Jata, 9
Algorta (Vizcaya), Spain, 48993
Centro Geroinnova Barcelona, Calle Mandoni n 17
Barcelona, Spain, 08004
Fundacio ACE, Institut Catala de Neurosciencies Aplicadas, C/Margues de Sentmenat 35-37
Barcelona, Spain, 08014
Institud d' Assistencia Sanitaria de Girona, Edifici La Republica - C/Dr. Castany, s/n
SALT (Girona), Spain, 17190
Sponsors and Collaborators
Avraham Pharmaceuticals Ltd
Investigators
Principal Investigator: Reinhold Schmidt, MD Medizinische Universitat Graz
  More Information

No publications provided

Responsible Party: Avraham Pharmaceuticals Ltd
ClinicalTrials.gov Identifier: NCT01354691     History of Changes
Other Study ID Numbers: CR100101/CO15570
Study First Received: May 1, 2011
Last Updated: July 22, 2013
Health Authority: Austria: Agency for Health and Food Safety
Germany: Federal Institute for Drugs and Medical Devices
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Croatia: Ministry of Health and Social Care
Serbia: Ethics Committee

Keywords provided by Avraham Pharmaceuticals Ltd:
Alzheimer's Disease
Dementia
Memory Loss
Cognitive Impairment
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Depression
Anxiety

Additional relevant MeSH terms:
Alzheimer Disease
Amnesia
Memory Disorders
Dementia
Cognition Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on April 17, 2014