Clinical trial NCT03316898: 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
Official title: A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Determine the Safety, Tolerability, Pharmacokinetics, and Brain Metabolic Response, Using FDG-PET, Following Administration of AGN-242071 Added to Standard-of-Care (Donepezil ± Memantine) in Participants With Mild to Moderate Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Alzheimer's Disease
Lead sponsor: Allergan
Sponsor class: INDUSTRY
First posted: 2017-10-20
Enrollment: 0
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


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.

Primary outcomes:
measure: 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
timeFrame: Baseline (Day -3 to Day -1) to Day 28
measure: Percentage of Participants with Treatment-Emergent Adverse Events (TEAE)
timeFrame: Day 1 to Day 35
measure: Percentage of Participants with Changes from Baseline in Clinically Significant Clinical Laboratory Values
timeFrame: Baseline (Day -3 to Day -1) to Day 35
measure: Percentage of Participants with Changes from Baseline in Clinically Significant Vital Signs
timeFrame: Baseline (Day -3 to Day -1) to Day 35
measure: Percentage of Participants with Changes from Baseline in Clinically Significant Electrocardiogram (ECG) Findings
timeFrame: Baseline (Day -3 to Day -1) to Day 35
measure: Percentage of Participants who have Suicidal Ideation or Behaviours as determined by Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline (Day 1) to Day 35
measure: Clearance of AGN-242071
timeFrame: Day 1 to Day 28
measure: Volume of Distribution of AGN-242071
timeFrame: Day 1 to Day 28
measure: Cmax: Maximum Plasma concentration for AGN-242071
timeFrame: Day 28
measure: AUC: Area Under the Curve for AGN-242071
timeFrame: Day 28
Secondary outcomes:
Other outcomes:
Locations:
city: Costa Mesa
country: United States
facility: ATP Clinical Research
state: California
city: Irvine
country: United States
facility: Irvine Center for Clinical Research
state: California
city: Lemon Grove
country: United States
facility: Synergy Research Centers
state: California
city: Long Beach
country: United States
facility: Collaborative Neuroscience
state: California
city: Long Beach
country: United States
facility: Alliance Research
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
Study officials:
affiliation: Allergan
name: Mitalee Tamhane, PhD
role: STUDY_DIRECTOR
References: