Alzheimer's DiseasePhase 2NCT01354691
Safety and Efficacy Study of Ladostigil in Mild to Moderate Probable Alzheimer's Disease
A Phase 2 study testing ladostigil hemitartrate in people with Alzheimer's Disease and Dementia, run by Avraham Pharmaceuticals Ltd at 19 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 to 85 years
- Conditions the study is for
- Alzheimer's Disease, Dementia, Memory Loss
- What is being tested?
- ladostigil hemitartrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 19 sitesin 5 countries
- Study dates
- Feb 2011to Mar 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
Show all 9Show fewer
- 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
Trial locations and contacts
19 sites in 5 countries.
19 sites in 5 countries
Croatia6 sites
General Hospital Pula, Negrijeva 6
Pula, 52100
General Hospital Zabok, Bracak 8
Zabok, 49210
Clinical Hospital Center Zagreb, Kispaticeva 12
Zagreb, 10000
Clinical Hospital Dubrava, Avenija Gojka Suska 6
Zagreb, 10000
Polyclinic Neuron, Salata 12
Zagreb, 10000
Psychiatric Hospital Vrapce, Bolnicka cesta 32
Zagreb, 10090
Austria4 sites
Medizinische Univeritat Graz, Universitatsklinik fur Neurologie, Auenbruggerplatz 22
Graz, 8036
Privatordination Horn, HamerlingstraBe 15
Horn, 3580
Allgemeines Krankenhaus der Stadt Linz, KrankenhausstraBe 9
Linz, 4020
Privatordination, Lainzerstrasse 20
Wein, 1130
Spain4 sites
CAE Oroitu Centro Atencion Especializada C/Jata, 9
Algorta, 48993
Centro Geroinnova Barcelona, Calle Mandoni n 17
Barcelona, 08004
Fundacio ACE, Institut Catala de Neurosciencies Aplicadas, C/Margues de Sentmenat 35-37
Barcelona, 08014
Institud d' Assistencia Sanitaria de Girona, Edifici La Republica - C/Dr. Castany, s/n
Salt, 17190
Germany3 sites
Klinische Forschung Hamburg GmbH, Hoheluftaussee 18
Hamburg, 20253
Klinische Forschung Schwerin GmbH, FriedrichstraBe 1
Schwerin, 19055
Studienzentrum Nordwest, Lange StraBe 23-25
Westerstede, 26655
Serbia2 sites
Clinical Centre of Serbia, Dr. Subotica 6
Belgrade, 11000
Military Medical Academy, Crnotravska 17
Belgrade, 11000
About this study
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
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
Read the 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.
- Conditions
- Alzheimer's Disease, Dementia, Memory Loss, Cognitive Impairment
- Being tested
- ladostigil hemitartrate
- Keywords
- 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
- Medical subject headings
- Alzheimer Disease, Dementia, Memory Disorders, Cognitive Dysfunction, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Neurodegenerative Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ladostigil hemitartrateDrug
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 group | Role | What they receive |
|---|---|---|
| ladostigil hemitartrate | Experimental | Ladostigil capsules 80 mg Receives: Drug: ladostigil hemitartrate |
| Placebo | Placebo comparator | Placebo capsules Receives: Drug: ladostigil hemitartrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
ADAS-Cog: Alzheimer's Disease Assessment Scale-Cognitive Subscale
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is a brief neuropsychological assessment used to assess the severity of cognitive symptoms of dementia, The ADAS-Cog consist of 11 questions:
Word Recall Task Naming Objects and Fingers Following Commands Constructional Praxis Ideational Praxis Orientation Word Recognition Task Remembering Test Directions Spoken Language Comprehension Word-Finding Difficulty
Item scores are summed.
Low total scores indicate better cognitive performance. Minimum score 0 is best and maximum is 70 - worst.
For the purposes of analyses the change from baseline is computed to each administration of the test.
Measured: 26 weeks
Secondary outcomes (4)
Neuropsychiatric Inventory (NPI)
The Neuropsychiatric Inventory (NPI) was developed to assess psychopathology in dementia patients. It evaluates 12 neuropsychiatric disturbances common in dementia: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, night-time behavior disturbances, and appetite and eating abnormalities. The severity and frequency of each neuropsychiatric symptom are rated on the basis of scripted questions administered to the patient's caregiver. Higher the score the more disturbed, lower score is thus better. Minimum score is 0 and maximum is 80.
Measured: 52 weeks
Cornell Scale for Depression in Dementia (CSDD)
The Cornell Scale for Depression in Dementia (CSDD) was developed specifically to assess signs and symptoms of major depression in dementia on the basis of a semi-structured interview of a qualified informant. The CSDD evaluates a broad spectrum of depressive signs and synptoms and includes items from other depression scales. Information is obtained from interview of the caregiver as well as from direct observation and interview of the patient CSDD is a 19 item scale assessing depressive status. Higher score more depression. The scale ranges from 0-no depression to 38 maximum depression.
Measured: 52 weeks
Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
The Activities of Daily Living ADCS-ADL is a caregiver-based ADL scale composed of 23 items developed for use in dementia clinical trials. It is designed to assess the patient's performance of both basic and instrumental activities of daily living such as those necessary for personal care, communicating and interacting with other people, maintaining a household, conducting hobbies and interests as well as making judgments and decisions. For each ADL, the caregiver is asked whether the patient attempted the activity during the past four weeks. If the answer is positive, the caregiver is then asked to choose the single most accurate definition of the patient's level of performance. Assessment of functional activity status is a 23 item scale measuring impairment in functioning. The scale total score ranges from 0-profound impairment to 30 normal functioning (no impairments)
Measured: 52 weeks
Mini-Mental State Examination
The MMSE is a frequently used screening instrument for AD drug studies. The instrument provides for evaluation of orientation, memory, attention, concentration, naming, repetition, comprehension, ability to create a sentence and to copy two intersecting polygons. This examination is frequently used by physicians in the original diagnosis of AD, and in its subsequent progression, because it can be easily performed in the routine care of patients. A lower score indicates more cognitive impairment. The highest (best) score is 30. The Mini-Mental State Examination, MMSE, is a 30-point questionnaire measures cognitive impairment to screen for dementia. Items are totaled. The scale ranges from 0-most impairment to 30 (normal) no impairment.
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2011 (estimated)
- Study startFeb 2011
- Primary completionSep 2012
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Avraham Pharmaceuticals Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Reinhold Schmidt, MD, Principal investigator, MEDIZINISCHE UNIVERSITAT GRAZ
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01354691
- Sponsor's protocol ID
- CR100101/CO15570
- Status last verified
- Jul 2018
- First submitted
- 1 May 2011
- Last updated
- 30 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01354691
- Acronym / sponsor ID
- CR100101/CO15570
- Conditions
- Alzheimer's Disease, Dementia, Memory Loss, Cognitive Impairment
- Keywords
- Alzheimer's Disease, Dementia, Memory Loss, Cognitive Impairment, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Neurodegenerative Diseases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Avraham Pharmaceuticals LtdIndustry (pharma, biotech, devices)
- Study start
- Feb 2011
- Primary completion
- Sep 2012 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 17 May 2011 (estimated)
- Results
- Posted 30 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ladostigil hemitartrate | Experimental | Drug: ladostigil hemitartrateLadostigil capsules 80 mg |
| Placebo | Placebo comparator | Drug: ladostigil hemitartratePlacebo capsules |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ladostigil hemitartrateFinal 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. | Drug | Placebo, ladostigil hemitartrate |
Primary outcome
ADAS-Cog: Alzheimer's Disease Assessment Scale-Cognitive Subscale
Time frame: 26 weeks
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is a brief neuropsychological assessment used to assess the severity of cognitive symptoms of dementia, The ADAS-Cog consist of 11 questions: Word Recall Task Naming Objects and Fingers Following Commands Constructional Praxis Ideational Praxis Orientation Word Recognition Task Remembering Test Directions Spoken Language Comprehension Word-Finding Difficulty Item scores are summed. Low total scores indicate better cognitive performance. Minimum score 0 is best and maximum is 70 - worst. For the purposes of analyses the change from baseline is computed to each administration of the test.
4 secondary outcomes
Neuropsychiatric Inventory (NPI)
Time frame: 52 weeks
Cornell Scale for Depression in Dementia (CSDD)
Time frame: 52 weeks
Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
Time frame: 52 weeks
Mini-Mental State Examination
Time frame: 52 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Reinhold Schmidt, MD principal investigator
MEDIZINISCHE UNIVERSITAT GRAZ
19 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ladostigil hemitartrate in people with Alzheimer's Disease and Dementia, run by Avraham Pharmaceuticals Ltd at 19 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Croatia, Austria, Spain, Germany, Serbia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ADAS-Cog: Alzheimer's Disease Assessment Scale-Cognitive Subscale (time frame: 26 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2020.