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Efficacy of ORM-12741 on Agitation/Aggression Symptoms in Alzheimer's Disease (Nebula)

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ClinicalTrials.gov Identifier: NCT02471196
Recruitment Status : Completed
First Posted : June 15, 2015
Last Update Posted : February 15, 2018
Sponsor:
Collaborator:
Janssen Pharmaceuticals
Information provided by (Responsible Party):
Orion Corporation, Orion Pharma

Brief 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.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: ORM-12741 Drug: Placebo Phase 2

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 308 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : August 14, 2015
Actual Primary Completion Date : October 9, 2017
Actual Study Completion Date : December 4, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ORM-12741 low dose
ORM-12741 low dose twice a day for 12 weeks.
Drug: ORM-12741
ORM-12741 low dose twice a day

Experimental: ORM-12741 high dose
ORM-12741 high dose twice a day for 12 weeks.
Drug: ORM-12741
ORM-12741 high dose twice a day

Placebo Comparator: Placebo
Placebo twice a day for 12 weeks.
Drug: Placebo
Placebo twice a day




Primary Outcome Measures :
  1. Efficacy on aggression/agitation symptoms measured by Neuropsychiatric Inventory Clinician Rating scale [ Time Frame: 12 weeks ]

Secondary Outcome Measures :
  1. 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 ]
  2. Efficacy on cognitive symptoms measured by Cognitive Drug Research computerized test battery [ Time Frame: 12 weeks ]
  3. Efficacy on daily living measured by Alzheimer's Disease Co-operative Study - Activities of Daily Living inventory [ Time Frame: 12 weeks ]
  4. Safety measured by assessing adverse events [ Time Frame: 12 weeks ]
  5. Plasma concentrations of ORM ORM-12741, metabolites and possible other Alzheimer's disease medication [ Time Frame: 12 weeks ]
  6. Efficacy on aggression/agitation symptoms measured by Cohen Mansfield Agitation Inventory [ Time Frame: 12 weeks ]
  7. Efficacy on cognitive symptoms measured by Alzheimer's Disease Assessment Scale [ Time Frame: 12 weeks ]
  8. Safety measured by vital signs [ Time Frame: 12 weeks ]
  9. Safety measured by electrocardiogram [ Time Frame: 12 weeks ]
  10. Safety measured by laboratory variables [ Time Frame: 12 weeks ]


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Ages Eligible for Study:   55 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02471196


Locations
Finland
Clinical Research Services Turku - CRST Oy
Turku, Finland
Sponsors and Collaborators
Orion Corporation, Orion Pharma
Janssen Pharmaceuticals
Investigators
Principal Investigator: Juha Rinne, Prof Clinical Research Services Turku - CRST Oy

Responsible Party: Orion Corporation, Orion Pharma
ClinicalTrials.gov Identifier: NCT02471196     History of Changes
Other Study ID Numbers: 3098012
First Posted: June 15, 2015    Key Record Dates
Last Update Posted: February 15, 2018
Last Verified: February 2018

Additional relevant MeSH terms:
Alzheimer Disease
Aggression
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Behavioral Symptoms