A FDG-PET Study of AGN-242071 Added to Standard-of-Care (Donepezil ± Memantine) for the Treatment of Participants With Mild to Moderate Alzheimer's Disease

Allergan

Status and phase: Withdrawn; Phase 1

Conditions: Alzheimer's Disease

Treatments: Drug: AGN-242071; Drug: Donepezil; Drug: Placebo; Drug: Memantine

Study type: Interventional

Funder types: Industry

Identifiers

NCT03316898

3142-101-001

Details and patient eligibility

About

This is a study to evaluate the brain metabolic response using Fluorodeoxyglucose Positron Emission Tomography (FDG-PET), safety, tolerability and pharmacokinetics of AGN-242071 in patients with mild to moderate Alzheimer's Disease on a stable dose of 10 mg donepezil with or without memantine standard of care.

Sex: All

Ages: 55 to 85 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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0 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Memantine

Drug: Placebo

Drug: Donepezil

AGN-242071 5 mg

Experimental group

Description:

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.

Treatment:

Drug: Memantine

Drug: Placebo

Drug: Donepezil

Drug: AGN-242071

AGN-242071 15 mg

Experimental group

Description:

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.

Treatment:

Drug: Memantine

Drug: Placebo

Drug: Donepezil

Drug: AGN-242071

AGN-242071 25 mg

Experimental group

Description:

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.

Treatment:

Drug: Memantine

Drug: Placebo

Drug: Donepezil

Drug: AGN-242071