Clinical trial NCT02820896 (phase 1, status: completed)
Conditions: alzheimer's disease
ICD codes: G30.8, G30.9, G30.0, G30.1
Drugs: placebo, ro7105705
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

        All participants

          -  Total body weight between 45 and 120 kilogram (kg), inclusive

          -  Agreement not to donate blood or blood products for transfusion for the duration of
             the study and for 1 year after final dose of study drug

          -  In good health, determined by no clinically significant findings from medical history,
             physical examination, 12-lead electrocardiogram (ECG), laboratory tests, and vital
             signs

          -  Clinical laboratory evaluations (including chemistry panel fasted [fasted at least 8
             hours], complete blood count (CBC), and urine analysis) within the reference range for
             the test laboratory, unless deemed not clinically significant by the investigator

          -  Negative test for selected drugs of abuse at screening and at check-in

          -  Agreement to use highly effective contraception measures

        Healthy Participants

          -  Ages 18-80 years inclusive

          -  No history of symptomatic cognitive decline and no concern about clinically
             significant cognitive impairment by the participant or by the investigator

        Participants who enroll into a cohort that requires lumbar puncture

          -  No contraindication to lumbar dural puncture, including coagulopathy, concomitant
             anticoagulation, thrombocytopenia, prior lumbar spinal surgery, or other factor that
             precludes safe lumbar puncture in the opinion of the investigator

        Participants with Alzheimer's disease

          -  Ages 50-80 years, inclusive

          -  The participant should be capable of completing assessments either alone or with the
             help of the caregiver

          -  Availability of a person (caregiver) who, in the investigator's judgment, has frequent
             and sufficient contact with the participant and is able to provide accurate
             information regarding the participant's cognitive and functional abilities, agrees to
             provide information at clinic visits, which require partner input for scale
             completion, and signs the necessary consent form

          -  Adequate visual and auditory acuity, in the investigator's judgment, sufficient to
             perform the neuropsychological testing

          -  Clinical diagnosis of probable Alzheimer's disease dementia based on National
             Institute on Aging-Alzheimer's Association criteria

          -  Screening mini-mental state examination (MMSE) score of 16-28 points, inclusive

          -  Screening Clinical Dementia Rating-Global Score (CDR-GS) of 0.5, 1.0, or 2.0

          -  Positive florbetapir amyloid positron emission tomography (PET) scan by qualitative
             read

          -  If already taking cholinesterase inhibitor and/or memantine therapy for Alzheimer's
             disease, on a stable dose for at least 4 weeks prior to screening. There should be no
             intent to, discontinue, or alter the dose of any Alzheimer's disease therapy for the
             duration of the study

        Exclusion Criteria:

        Any participants

          -  Pregnant or lactating, or intending to become pregnant within 16 weeks after last dose
             of study drug

          -  Participation in a clinical trial within 30 days before randomization; use of any
             experimental oral therapy within 30 days or 5 half-lives prior to Day 1, whichever is
             greater; or use of any biologic therapy within 12 weeks or 5 half-lives prior to Day
             1, whichever is greater

          -  Any non-experimental vaccine within 2 weeks of randomization, until 2 weeks after the
             last dose

          -  Surgery or hospitalization during the 4 weeks prior to screening

          -  Planned procedure or surgery during the study

          -  Blood transfusion within 8 weeks prior to screening

          -  Donation or loss of blood (excluding the volume of blood that will be drawn during
             screening procedures) as follows: 50-499 milliliters (mL) of blood within 30 days or
             greater than (>) 499 mL of blood within 56 days prior to study drug administration

          -  Poor peripheral venous access

          -  Positive for hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), or
             human immunodeficiency virus (HIV) antibody

          -  Illicit drug or alcohol abuse within 12 months prior to screening, in the
             investigator's judgment

          -  Administration of any herbal or nutritional supplements (with the exception of
             standard vitamins and calcium supplements) within 7 days prior to study dose

          -  Past history of seizures, prior traumatic brain injury, schizophrenia, schizoaffective
             disorder, or bipolar disorder

          -  At risk of suicide in the opinion of the investigator

          -  Serious infection requiring oral and IV antibiotics within 30 days prior to screening

          -  Any serious medical condition or abnormality in clinical laboratory tests;
             systemically, clinically immunocompromised because of continuing effects of
             immune-suppressing medication

        Participants with Alzheimer's disease

          -  History or presence of clinically evident vascular disease potentially affecting the
             brain

          -  History or presence of stroke within the previous 2 years or documented history of
             transient ischemic attack within the previous 12 months

          -  History or presence of intracranial tumor that is clinically relevant in the opinion
             of the investigator

          -  Presence of infections that affect brain function or history of infections that
             resulted in neurologic sequelae

          -  History or presence of central nervous system (CNS) or systemic autoimmune disorders
             potentially causing progressive neurologic disease with associated cognitive deficits

          -  History or presence of a neurologic disease other than Alzheimer's disease that may
             affect cognition

          -  Magnetic resonance imaging (MRI) evidence of 1) more than two lacunar infarcts, 2) any
             territorial infarct less than (>) 1 centimeters (cm), or 3) significant fluid
             attenuated inversion recovery (FLAIR) hyperintense lesions in the cerebral white
             matter that may, in the investigator's opinion, contribute to cognitive dysfunction