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

Tracking Information
First Submitted Date ICMJE	May 1, 2011
First Posted Date ICMJE	May 17, 2011
Last Update Posted Date	July 23, 2013
Study Start Date ICMJE	February 2011
Actual Primary Completion Date	September 2012 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: May 14, 2011)	ADAS-Cog: Alzheimer's Disease Assessment Scale-Cognitive Subscale [ Time Frame: 26 weeks ]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 ]Number and severity of adverse events across trial period.
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01354691 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: May 14, 2011)	Neuropsychiatric Inventory (NPI) [ Time Frame: 6, 15, 26, 39 and 52 weeks ]Assessment of behavioral and psychological symptoms of disease; Cornell Scale for Depression in Dementia (CSDD) [ Time Frame: 6, 15, 26, 39 and 52 weeks ]Assessment of depressive status; Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) [ Time Frame: 6, 15, 26, 39 and 52 weeks ]Assessment of functional activity status; Mini-Mental State Examination (MMSE) [ Time Frame: 6, 15, 26, 39 and 52 weeks ]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 ]11 item, unmodified ADAS-Cog (total possible score of 70)
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Safety and Efficacy Study of Ladostigil in Mild to Moderate Probable Alzheimer's Disease
Official Title ICMJE	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
Brief Summary	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
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.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Alzheimer's Disease; Dementia; Memory Loss; Cognitive Impairment
Intervention ICMJE	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.
Study Arms	Experimental: ladostigil hemitartrate; Intervention: Drug: ladostigil hemitartrate
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: July 22, 2013)	201
Original Estimated Enrollment ICMJE; (submitted: May 14, 2011)	188
Actual Study Completion Date	March 2013
Actual Primary Completion Date	September 2012 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	60 Years to 85 Years (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Austria, Croatia, Germany, Serbia, Spain
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01354691
Other Study ID Numbers ICMJE	CR100101/CO15570
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Avraham Pharmaceuticals Ltd
Study Sponsor ICMJE	Avraham Pharmaceuticals Ltd
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Reinhold Schmidt, MD MEDIZINISCHE UNIVERSITAT GRAZ
PRS Account	Avraham Pharmaceuticals Ltd
Verification Date	July 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP