Alzheimer's DiseasePhase 2NebulaNCT02471196
Efficacy of ORM-12741 on Agitation/Aggression Symptoms in Alzheimer's Disease
A Phase 2 study testing ORM-12741 in people with Alzheimer's Disease, run by Orion Corporation, Orion Pharma at 1 site in Finland.
Trial summary
This study evaluates the effect of ORM-12741 on agitation/aggression symptoms in Alzheimer's disease. Two thirds of the patients will receive ORM-12741 and one third will receive placebo. Read more about this study
- Who is it for?
- Ages 55 to 90 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- ORM-12741
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 308 participants
- Where
- 1 siteFinland
- Study dates
- 14 Aug 2015to 4 Dec 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 55 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent (IC) for participation in the study (co-signed by the subject's next of kin or caregiver, or other legally acceptable representative.
- Written IC obtained from a consistently available caregiver informant who is knowledgeable of the subject's condition and its progression and is willing to accompany the subject to all visits and supervise the administration of the study medication.
- Age of 55-90 years (inclusive).
- Male or female subjects with diagnosis of probable Alzheimer's Disease.
- Brain imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) consistent with a diagnosis of Alzheimer's Disease (within 18 months or at screening).
- Mini-mental state examination (MMSE) score between 10-24 (inclusive).
- Clinically significant agitation meeting the International Psychogeriatric Association Provisional Criteria for Agitation in Cognitive Impairment. The agitation symptoms need to have been present for at least 4 weeks before the screening visit.
- Neuropsychiatric Inventory agitation/aggression item score at least 4 at screening visit.
Who cannot join
- Modified Hachinski Ischemia Score (MHIS) > 4.
- Changes in AChE inhibitor (donepezil, rivastigmine or galantamine) dosing within 2 months prior to screening.
- Changes in memantine dosing within 2 months prior to the screening.
- Changes in antidepressant dosing or addition of another antidepressant medication within 2 months prior to the screening.
- Use of antipsychotics at any dose within 1 month prior to screening.
- Use of benzodiazepines, other than short-acting sleep medications, for night at a maximum of 3 nights/week, within 2 months prior to screening.
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- Use of any anticholinergic medication within 2 months prior to screening.
- Current use (within the 30 days prior to screening) of medications with known relevant alpha-2C AR affinity (e.g. mirtazapine, mianserin, clonidine, guanfacine or tizanidine) or with high noradrenaline transporter affinity (reboxetine, venlafaxine or duloxetine).
- Current use of other psychotropic agents, unless the dosing has been stable during the last 2 months prior to the screening.
- Myocardial infarction or other clinically significant ischemic cardiac disease, heart failure, or arrhythmia tendency within the past 2 years.
- Current or history of malignancy within 5 years before screening.
- Suicidal ideation in the 6 months before screening or current suicide risk based on the Colombia-Suicide Severity Rating Scale (C-SSRS) (items 4 and 5 exclusionary) or current risk of suicide based on the investigator's judgement.
- Specific findings in MRI or CT that could in the opinion of the investigator affect cognitive function (such as cortical infarct or silent lacuna in a region known to affect cognition).
- Supine heart rate < 48 bpm or > 100 bpm.
- Systolic blood pressure (SBP) > 160 mmHg or diastolic blood pressure (DBP) > 100 mmHg after a 5-minute rest.
- Symptomatic orthostatic hypotension.
- QTc-Fridericia (QTcF) repeatedly > 450 ms in males or > 470 ms in females.
- Clinically significantly abnormal thyroid-stimulating hormone (TSH), vitamin B12 or folate serum levels at screening.
- Resides in a skilled nursing facility.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy of ORM-12741 on Agitation/Aggression Symptoms in Patients With Alzheimer's Disease: A Randomised, Double-blind, Placebo-controlled, Parallel Group, Multicentre Study of 12 Weeks
This study evaluates the effect of ORM-12741 on agitation/aggression symptoms in Alzheimer's disease. Two thirds of the patients will receive ORM-12741 and one third will receive placebo.
Read the detailed description
ORM-12741 is a potent and selective alpha-2C adrenoceptor (AR)-antagonist. Previous results suggest that the compound may have positive effects on both cognitive and neuropsychiatric symptoms of Alzheimer's Disease. In this study, the effect of ORM-12741 will be evaluated on agitation/aggression symptoms and other neuropsychiatric symptoms. Furthermore, cognition and psychotic and depressive symptoms will be evaluated.
- Conditions
- Alzheimer's Disease
- Being tested
- ORM-12741, Placebo
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ORM-12741Drug
ORM-12741 low dose twice a day
ORM-12741Drug
ORM-12741 high dose twice a day
PlaceboDrug
Placebo twice a day
| Study group | Role | What they receive |
|---|---|---|
| ORM-12741 low dose | Experimental | ORM-12741 low dose twice a day for 12 weeks. Receives: Drug: ORM-12741 |
| ORM-12741 high dose | Experimental | ORM-12741 high dose twice a day for 12 weeks. Receives: Drug: ORM-12741 |
| Placebo | Placebo comparator | Placebo twice a day for 12 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy on aggression/agitation symptoms measured by Neuropsychiatric Inventory Clinician Rating scale
Measured: 12 weeks
Secondary outcomes (10)
Efficacy on aggression/agitation symptoms and overall clinical status measured by Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change
Measured: 12 weeks
Efficacy on cognitive symptoms measured by Cognitive Drug Research computerized test battery
Measured: 12 weeks
Efficacy on daily living measured by Alzheimer's Disease Co-operative Study - Activities of Daily Living inventory
Measured: 12 weeks
Safety measured by assessing adverse events
Measured: 12 weeks
Plasma concentrations of ORM ORM-12741, metabolites and possible other Alzheimer's disease medication
Measured: 12 weeks
Efficacy on aggression/agitation symptoms measured by Cohen Mansfield Agitation Inventory
Measured: 12 weeks
Efficacy on cognitive symptoms measured by Alzheimer's Disease Assessment Scale
Measured: 12 weeks
Safety measured by vital signs
Measured: 12 weeks
Safety measured by electrocardiogram
Measured: 12 weeks
Safety measured by laboratory variables
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2015 (estimated)
- Study start14 Aug 2015
- Primary completion9 Oct 2017
- Study completion4 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 308 participants (actual)
Sponsor and investigators
- Lead sponsor
- Orion Corporation, Orion Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Janssen Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Juha Rinne, Prof, Principal investigator, Clinical Research Services Turku - CRST Oy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02471196
- Sponsor's protocol ID
- 3098012
- Acronym
- Nebula
- Status last verified
- Feb 2018
- First submitted
- 8 Jun 2015
- Last updated
- 15 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of ORM-12741 on Agitation/Aggression Symptoms in Patients With Alzheimer's Disease: A Randomised, Double-blind, Placebo-controlled, Parallel Group, Multicentre Study of 12 Weeks
- ClinicalTrials.gov ID
- NCT02471196
- Acronym / sponsor ID
- Nebula / 3098012
- Conditions
- Alzheimer's Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 308 participants (actual)
- Lead sponsor
- Orion Corporation, Orion PharmaIndustry (pharma, biotech, devices)
- Collaborators
- Janssen Pharmaceuticals
- Study start
- 14 Aug 2015 (actual)
- Primary completion
- 9 Oct 2017 (actual)
- Study completion
- 4 Dec 2017 (actual)
- First posted
- 15 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the effect of ORM-12741 on agitation/aggression symptoms in Alzheimer's disease. Two thirds of the patients will receive ORM-12741 and one third will receive placebo.
Detailed description
ORM-12741 is a potent and selective alpha-2C adrenoceptor (AR)-antagonist. Previous results suggest that the compound may have positive effects on both cognitive and neuropsychiatric symptoms of Alzheimer's Disease. In this study, the effect of ORM-12741 will be evaluated on agitation/aggression symptoms and other neuropsychiatric symptoms. Furthermore, cognition and psychotic and depressive symptoms will be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ORM-12741 low dose | Experimental | Drug: ORM-12741ORM-12741 low dose twice a day for 12 weeks. |
| ORM-12741 high dose | Experimental | Drug: ORM-12741ORM-12741 high dose twice a day for 12 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo twice a day for 12 weeks. |
Who may qualify
- Ages
- 55 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Written informed consent (IC) for participation in the study (co-signed by the subject's next of kin or caregiver, or other legally acceptable representative.
- Written IC obtained from a consistently available caregiver informant who is knowledgeable of the subject's condition and its progression and is willing to accompany the subject to all visits and supervise the administration of the study medication.
- Age of 55-90 years (inclusive).
- Male or female subjects with diagnosis of probable Alzheimer's Disease.
- Brain imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) consistent with a diagnosis of Alzheimer's Disease (within 18 months or at screening).
Key exclusion criteria (19 listed)
- Modified Hachinski Ischemia Score (MHIS) > 4.
- Changes in AChE inhibitor (donepezil, rivastigmine or galantamine) dosing within 2 months prior to screening.
- Changes in memantine dosing within 2 months prior to the screening.
- Changes in antidepressant dosing or addition of another antidepressant medication within 2 months prior to the screening.
- Use of antipsychotics at any dose within 1 month prior to screening.
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 |
|---|---|---|
| ORM-12741ORM-12741 low dose twice a day | Drug | ORM-12741 low dose |
| ORM-12741ORM-12741 high dose twice a day | Drug | ORM-12741 high dose |
| PlaceboPlacebo twice a day | Drug | Placebo |
Primary outcome
Efficacy on aggression/agitation symptoms measured by Neuropsychiatric Inventory Clinician Rating scale
Time frame: 12 weeks
10 secondary outcomes
Efficacy on aggression/agitation symptoms and overall clinical status measured by Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change
Time frame: 12 weeks
Efficacy on cognitive symptoms measured by Cognitive Drug Research computerized test battery
Time frame: 12 weeks
Efficacy on daily living measured by Alzheimer's Disease Co-operative Study - Activities of Daily Living inventory
Time frame: 12 weeks
Safety measured by assessing adverse events
Time frame: 12 weeks
Plasma concentrations of ORM ORM-12741, metabolites and possible other Alzheimer's disease medication
Time frame: 12 weeks
Efficacy on aggression/agitation symptoms measured by Cohen Mansfield Agitation Inventory
Time frame: 12 weeks
Efficacy on cognitive symptoms measured by Alzheimer's Disease Assessment Scale
Time frame: 12 weeks
Safety measured by vital signs
Time frame: 12 weeks
Safety measured by electrocardiogram
Time frame: 12 weeks
Safety measured by laboratory variables
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2018.
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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.
Juha Rinne, Prof principal investigator
Clinical Research Services Turku - CRST Oy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ORM-12741 in people with Alzheimer's Disease, run by Orion Corporation, Orion Pharma at 1 site in Finland.
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 8 inclusion and 19 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 15 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Efficacy on aggression/agitation symptoms measured by Neuropsychiatric Inventory Clinician Rating scale (time frame: 12 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 15 Feb 2018.