Clinical trial NCT02471196 (phase 2, status: completed)
Conditions: alzheimer's disease
ICD codes: G30.8, G30.9, G30.0, G30.1
Drugs: orm-12741, orm-12741, placebo
SMILES: COC[C@@]1(C)CCCN2CCC3=C(OC4=CC=CC=C34)[C@H]12, COC[C@@]1(C)CCCN2CCC3=C(OC4=CC=CC=C34)[C@H]12, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility 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.