Alzheimer's DiseasePhase 1NCT03316898
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
A Phase 1 study testing AGN-242071, Donepezil and Memantine in people with Alzheimer's Disease, run by Allergan at 6 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 to 85 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- AGN-242071, Donepezil and Memantine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 6 sitesUnited States
- Study dates
- 30 Sep 2018to 4 Nov 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 25Show fewer
- 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 locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
ATP Clinical Research
Costa Mesa, California, 94105
Irvine Center for Clinical Research
Irvine, California, 92614
Synergy Research Centers
Lemon Grove, California, 91945
Collaborative Neuroscience
Long Beach, California, 90806
Alliance Research
Long Beach, California, 90807
Syrentis Clinical Research
Santa Ana, California, 92705
About this study
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
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
- Being tested
- AGN-242071, Placebo, Donepezil, Memantine
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AGN-242071Drug
AGN-242071 capsules administered once daily to patients receiving donepezil 10 mg with or without memantine as prescribed per standard of care.
PlaceboDrug
Placebo capsules once daily to patients receiving donepezil 10 mg with or without memantine as prescribed per standard of care.
DonepezilDrug
Donepezil 10 mg as prescribed by the physician as per standard of care.
MemantineDrug
Memantine as prescribed by the physician as per standard of care.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: AGN-242071; Drug: Placebo; Drug: Donepezil; Drug: Memantine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 1 to Day 28
Cmax: Maximum Plasma concentration for AGN-242071
Measured: Day 28
AUC: Area Under the Curve for AGN-242071
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2017
- Study start30 Sep 2018 (estimated)
- Primary completion4 Nov 2018 (estimated)
- Study completion4 Nov 2018 (estimated)
Why it stopped: Business decision to stop the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Allergan
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mitalee Tamhane, PhD, Study director, Allergan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03316898
- Sponsor's protocol ID
- 3142-101-001
- Status last verified
- Oct 2018
- First submitted
- 18 Oct 2017
- Last updated
- 2 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03316898
- Acronym / sponsor ID
- 3142-101-001
- Conditions
- Alzheimer's Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Business decision to stop the study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- AllerganIndustry (pharma, biotech, devices)
- Study start
- 30 Sep 2018 (estimated)
- Primary completion
- 4 Nov 2018 (estimated)
- Study completion
- 4 Nov 2018 (estimated)
- First posted
- 20 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo, Drug: Donepezil, Drug: MemantineTwo 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. |
| AGN-242071 5 mg | Experimental | Drug: AGN-242071, Drug: Placebo, Drug: Donepezil, Drug: MemantineOne 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. |
| AGN-242071 15 mg | Experimental | Drug: AGN-242071, Drug: Placebo, Drug: Donepezil, Drug: MemantineAGN-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. |
| AGN-242071 25 mg | Experimental | Drug: AGN-242071, Drug: Placebo, Drug: Donepezil, Drug: MemantineAGN-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. |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AGN-242071AGN-242071 capsules administered once daily to patients receiving donepezil 10 mg with or without memantine as prescribed per standard of care. | Drug | AGN-242071 15 mg, AGN-242071 25 mg, AGN-242071 5 mg |
| PlaceboPlacebo capsules once daily to patients receiving donepezil 10 mg with or without memantine as prescribed per standard of care. | Drug | AGN-242071 15 mg, AGN-242071 25 mg, AGN-242071 5 mg, Placebo |
| DonepezilDonepezil 10 mg as prescribed by the physician as per standard of care. | Drug | AGN-242071 15 mg, AGN-242071 25 mg, AGN-242071 5 mg, Placebo |
| MemantineMemantine as prescribed by the physician as per standard of care. | Drug | AGN-242071 15 mg, AGN-242071 25 mg, AGN-242071 5 mg, Placebo |
Primary outcome
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
Time frame: Baseline (Day -3 to Day -1) to Day 28
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.
Percentage of Participants with Treatment-Emergent Adverse Events (TEAE)
Time frame: Day 1 to Day 35
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.
Percentage of Participants with Changes from Baseline in Clinically Significant Clinical Laboratory Values
Time frame: Baseline (Day -3 to Day -1) to Day 35
Clinical laboratory safety tests include Chemistry, Hematology and Urinalysis.
Percentage of Participants with Changes from Baseline in Clinically Significant Vital Signs
Time frame: Baseline (Day -3 to Day -1) to Day 35
Vital signs include systolic and diastolic blood pressure, pulse rate, weight, respiration rate, and temperature.
Percentage of Participants with Changes from Baseline in Clinically Significant Electrocardiogram (ECG) Findings
Time frame: Baseline (Day -3 to Day -1) to Day 35
A standard 12-lead ECG will be performed.
Percentage of Participants who have Suicidal Ideation or Behaviours as determined by Columbia-Suicide Severity Rating Scale (C-SSRS)
Time frame: Baseline (Day 1) to Day 35
The C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation and suicidal behavior since the last visit.
Clearance of AGN-242071
Time frame: Day 1 to Day 28
Clearance will be determined utilizing a population pharmacokinetic (PK) approach implemented in non-linear mixed effects modeling (NONMEM®) software.
Volume of Distribution of AGN-242071
Time frame: Day 1 to Day 28
Volume of Distribution will be determined utilizing a population PK approach implemented in NONMEM® software.
Cmax: Maximum Plasma concentration for AGN-242071
Time frame: Day 28
AUC: Area Under the Curve for AGN-242071
Time frame: Day 28
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mitalee Tamhane, PhD study director
Allergan
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AGN-242071, Donepezil and Memantine in people with Alzheimer's Disease, run by Allergan at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 2 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: Baseline (Day -3 to Day -1) to Day 28). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2018.