A FDG-PET Study of AGN-242071 Added to Standard-of-Care (... | NCT03316898

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Two placebo capsules once daily for 28 Days. All participants are on a stable dose of 10 mg donepezil and, if receiving memantine, also on a stable dose of memantine as prescribed by the physician as per standard of care.	Drug: Placebo Drug: Donepezil Drug: Memantine
AGN-242071 5 mg	Experimental	One AGN-242071 5 mg capsule plus one placebo capsule once daily for 28 days. All participants are on a stable dose of 10 mg donepezil and, if receiving memantine, also on a stable dose of memantine as prescribed by the physician as per standard of care.	Drug: AGN-242071 Drug: Placebo Drug: Donepezil Drug: Memantine
AGN-242071 15 mg	Experimental	AGN-242071 starting at a dose of one 5 mg capsule plus one placebo capsule once daily for 5 days followed by AGN-242071 15 mg total dose (one 5 mg and one 10 mg capsules) once daily on Days 6 to 28. Dose can be adjusted based on safety and tolerability. All participants are on a stable dose of 10 mg donepezil and, if receiving memantine, also on a stable dose of memantine as prescribed by the physician as per standard of care.	Drug: AGN-242071 Drug: Placebo Drug: Donepezil Drug: Memantine
AGN-242071 25 mg	Experimental	AGN-242071 starting at a dose of one 5 mg capsule plus one placebo capsule once daily for 5 days followed by AGN-24071 15 mg total dose (one 5 mg and one 10 mg capsules) once daily on Days 6 to 10 followed by AGN-242071 25 mg total dose (one 5 mg and one 20 mg capsules) on Days 11 to 28. Dose can be adjusted based on safety and tolerability. All participants are on a stable dose of 10 mg donepezil and, if receiving memantine, also on a stable dose of memantine as prescribed by the physician as per standard of care.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
AGN-242071	Drug	AGN-242071 capsules administered once daily to patients receiving donepezil 10 mg with or without memantine as prescribed per standard of care.	AGN-242071 15 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change from Baseline in Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Metabolic Measure of Standard Uptake Value Ratio (SUVR) for Whole Brain, Hippocampal and Dorsolateral Prefrontal Cortices	The effects of AGN-242071 on brain metabolic activity or glucose metabolism will be determined using the FDG-PET scan by reporting results as SUVR.	Baseline (Day -3 to Day -1) to Day 28
Percentage of Participants with Treatment-Emergent Adverse Events (TEAE)	An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE that occurs during the treatment period will be considered a TEAE if it was not present before the first dose or if it was present but increased in severity during the treatment period.	Day 1 to Day 35
Percentage of Participants with Changes from Baseline in Clinically Significant Clinical Laboratory Values	Clinical laboratory safety tests include Chemistry, Hematology and Urinalysis.	Baseline (Day -3 to Day -1) to Day 35
Percentage of Participants with Changes from Baseline in Clinically Significant Vital Signs	Vital signs include systolic and diastolic blood pressure, pulse rate, weight, respiration rate, and temperature.	Baseline (Day -3 to Day -1) to Day 35
Percentage of Participants with Changes from Baseline in Clinically Significant Electrocardiogram (ECG) Findings	A standard 12-lead ECG will be performed.	Baseline (Day -3 to Day -1) to Day 35
Percentage of Participants who have Suicidal Ideation or Behaviours as determined by Columbia-Suicide Severity Rating Scale (C-SSRS)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnostic evidence of probable Alzheimer's Disease (AD) per the 2011 National Institutes of Aging-Alzheimer's Association (NIA-AA) criteria
Participants receiving donepezil at a stable dose of 10 mg daily with or without stable dose memantine for at least 6 weeks prior to the screening visit.

Exclusion Criteria:

Participants with illness apart from AD that could contribute to cognitive dysfunction
History of clinically significant suicidal ideation within the past 6 months
Thyroid disease unless the participant is euthyroid and stable on treatment for at least 3 months prior to screening
Participants with a personal or family history of congenital long QT syndrome or sudden death
Clinically significant cardiovascular disease in the past 6 months prior to screening
Participants with signs and symptoms of peripheral vascular disease (PVD)
A transient ischemic attack or other acute ischemic event affecting the brain, spinal cord, or peripheral circulation in the past 6 months prior to screening
Any history of cerebrovascular accident or stroke
Any history of a seizure disorder other than a single febrile seizure
Pulmonary disease or evidence of clinically significant moderate or severe pulmonary symptoms
History of cancer within the last 5 years
Evidence or history of diabetes mellitus Type 1
Any significant sensory (eg, moderate to severely impaired hearing or severely impaired vision) or hand movement difficulties that would prevent participants from completing the behavioral assessments of the study
Treatment with cholinesterase inhibitors other than donepezil or other cholinomimetics within 12 weeks of the baseline visit
Treatment with memantine not in combination with donepezil within 12 weeks of the baseline Visit
Participants who have been on anticholinergic and/or antimuscarinic treatment including overactive bladder treatments, antihistamines, antipsychotics, and tricyclic antidepressants, within 12 weeks prior to the baseline visit
Participants who have been on drugs that are strong inhibitors of CYP2D6 or CYP2C9 (eg, quinidine, paroxetine, fluoxetine, terbinafine, bupropion), or that are moderate or strong inhibitors of CYP3A4 (eg, erythromycin, ketoconazole, rifampicin, fluconazole, carbamazepine) within 21 days prior to the baseline visit
Participants who are taking any moderate or strong inducers of CYP3A4 (eg, carbamazepine, phenytoin, rifampin, modafinil, and herbal preparations containing St. John's wort) or strong inducers of CYP2C9 within 21 days prior to the baseline visit
Participants who have been on other drugs that could affect cognition (eg, benzodiazepines or gamma-aminobutyric acid A (GABAA) receptor agonists used as anxiolytics, sedative-hypnotics) or over-the-counter (OTC) sleeping aids within 12 weeks prior to the baseline visit
Participants who have been on hormone replacement therapy, thyroid supplement, vitamin E, or vitamin B12 unless at a stable dose for 4 weeks before the baseline visit
Use of an active Alzheimer's disease vaccine within 2 years prior to screening or monoclonal antibody for treatment of AD within 1 year prior to screening
Positive test results for anti-human immunodeficiency virus (anti-HIV) type 1 and 2, hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus (anti-HCV) at screening
Positive test results for urine drug screen for methadone, cocaine, tetrahydrocannabinol, benzodiazepines, tricyclic antidepressants, barbiturates, phencyclidine, amphetamines, methamphetamine, and opiates at screening or baseline visit
Participants with a body weight of less than 40 kg
Consumption of food or drinks containing grapefruit juice, cranberry, pomegranate, star fruit, grapefruit, pomelos, exotic citrus fruits or Seville orange or of alcohol within 72 hours before administration of study treatment.

Facility	Status	City	State	ZIP	Country	Contacts
ATP Clinical Research		Costa Mesa	California	94105	United States
Irvine Center for Clinical Research

ID	Term
D003704	Dementia
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D024801	Tauopathies
D019636	Neurodegenerative Diseases
D019965	Neurocognitive Disorders
D001523	Mental Disorders

ID	Term
D000077265	Donepezil
D008559	Memantine

ID	Term
D007189	Indans
D007192	Indenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D010880	Piperidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011083	Polycyclic Compounds
D000547	Amantadine
D000218	Adamantane
D001952	Bridged-Ring Compounds