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

NCT03316898 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 3142-101-001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 6

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.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (10)

• 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)

  The C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation and suicidal behavior since the last visit.

  Baseline (Day 1) to Day 35

• Clearance of AGN-242071

  Clearance will be determined utilizing a population pharmacokinetic (PK) approach implemented in non-linear mixed effects modeling (NONMEM®) software.

  Day 1 to Day 28

• Volume of Distribution of AGN-242071

  Volume of Distribution will be determined utilizing a population PK approach implemented in NONMEM® software.

  Day 1 to Day 28

• Cmax: Maximum Plasma concentration for AGN-242071

  Day 28

• AUC: Area Under the Curve for AGN-242071

  Day 28

Study Arms (4)

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.

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

Interventions

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; AGN-242071 25 mg; AGN-242071 5 mg

Placebo DRUG

Placebo capsules once daily to patients receiving donepezil 10 mg with or without memantine as prescribed per standard of care.

AGN-242071 15 mg; AGN-242071 25 mg; AGN-242071 5 mg; Placebo

Donepezil DRUG

Donepezil 10 mg as prescribed by the physician as per standard of care.

AGN-242071 15 mg; AGN-242071 25 mg; AGN-242071 5 mg; Placebo

Memantine DRUG

Memantine as prescribed by the physician as per standard of care.

AGN-242071 15 mg; AGN-242071 25 mg; AGN-242071 5 mg; Placebo

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Allergan: lead

Study Sites (6)

ATP Clinical Research

Costa Mesa, California, 94105, United States

Location

Irvine Center for Clinical Research

Irvine, California, 92614, United States

Location

Synergy Research Centers

Lemon Grove, California, 91945, United States

Location

Collaborative Neuroscience

Long Beach, California, 90806, United States

Location

Alliance Research

Long Beach, California, 90807, United States

Location

Syrentis Clinical Research

Santa Ana, California, 92705, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Donepezil; Memantine

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Amantadine; Adamantane; Bridged-Ring Compounds

Study Officials

• Mitalee Tamhane, PhD

  Allergan

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2017
• First Posted: October 20, 2017
• Study Start: September 30, 2018
• Primary Completion: November 4, 2018
• Study Completion: November 4, 2018
• Last Updated: November 2, 2018

Record last verified: 2018-10

Locations

US (6)