A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Multicenter Study of Buntanetap in Participants With Mild to Moderate Alzheimer's Disease
A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Multicenter Study of Buntanetap in Participants With Mild to Moderate Alzheimer's Disease
The purpose of this study is to measure efficacy and safety of three different doses of buntanetap/Posiphen compared with placebo in participants with mild to moderate Alzheimer's disease.
Study details include:
The double-blind treatment duration will include a screening period of up to 42 days followed by 12 weeks of treatment at home.
The study duration will be 4-5 months. There will be 4 in-clinic visits and 1 phone call.
320 mild to moderate AD participants will be randomized to 7.5 mg, 15 mg, 30mg of buntanetap/Posiphen once daily (QD) or placebo. If they provide informed consent, they will undergo a Screening Visit, and if they are considered eligible per the inclusion and exclusion criteria, they will proceed to participate in the treatment period. Randomized participants will visit the clinic for the first-time dosing in clinic, followed by an at home dosing period of 12 weeks, with daily administration of 7.5 mg, 15 mg or 30 mg of buntanetap/Posiphen or placebo. Participants will be required to visit clinics Day 0 (baseline), 6 weeks, and 12 weeks (end-of-trial), where they will undergo study procedures that include safety assessments (AE and concomitant medication monitoring, 12-lead ECGs, clinical laboratory testing, vital signs assessments, and physical examinations) and psychometric tests (Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11), Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Scale (ADCS-ADL), Digital Symbol Substitution Test (DSST), Mini Mental State Examination (MMSE)). At the end of blood sampling, the participants will need to stay for a minimum of 1 hour of observation. After all end-of-study procedures are complete, the subject will be discharged to home. A 24-hour follow-up call will occur after all clinical visits to assess the participants current condition and if there are any additional adverse events or questions.
The study will be a 12-weeks, placebo-controlled and double-blind trial: participants, investigators and the sponsor will be blinded to the participants' treatment.
Qualified participants will be randomly assigned at a 1:1:1:1 ratio to one of the four treatment arms: buntanetap/Posiphen 7.5 mg, buntanetap/Posiphen 15 mg, buntanetap/Posiphen 30mg, and placebo, through an Interactive Randomization System, after a screening period of up to 42 days.
ADAS-Cog 11, ADCS-CGIC, ADCS-ADL, DSST, and MMSE will be assessed by clinicians who have successfully completed the requisite certifications/trainings for each assessment.
One interim analysis is planned. It will take place when 90 enrolled subjects (~30%) have completed the Week 6 assessments to re-assess the sample size. No interim analyses are planned for the purpose of stopping the study early for futility.
Inclusion Criteria:
Diagnosis of Alzheimer's disease according to National Institute on Aging and National Institute on Aging and Alzheimer's Association criteria for probable AD
Male or female aged 55 - 85 years.
MMSE 14-24.
Have a study partner who will provide written informed consent to participate, is in frequent contact with the participant (defined as at least 10 hours per week) and will accompany the participant to study visits at designated times.
Female participants of childbearing potential* must have a negative urine pregnancy test at Screening, must be non-lactating and must agree to use a highly effective method of contraception (i.e., a method resulting in a failure rate of less than 1% per year when used consistently and correctly) during the trial and for 4 weeks after the last dose of trial treatment, such as:
Male participants must be sterile or sexually inactive or agree not to father a child during the study and one month after the last dose of study medication and must agree to use a barrier method for contraception. Female partners of male subject must adopt a highly effective method of contraception with a failure rate of less than 1% per year when used consistently and correctly such as:
Participants can provide written informed consent. If PI deems that participant cannot fully understand the consent form to give consent, their legally authorized representative (LARs) can provide written informed consent. Participants can comply with scheduled visits, and other study-related procedures to complete the study with the help of the study partner.
No evidence of current suicidal ideation or previous suicide attempt in the past 2 months as evaluated in the Columbia Suicide Severity Rating Scale nor suicidal behavior in the past 6 months as per investigator.
Stability of permitted medications for at least 4 weeks prior to screening.
Adequate visual and hearing ability (physical ability to perform all the study assessments) as per investigator.
Good general health with no disease expected to interfere with the study as per investigator.
Exclusion Criteria:
Has a history of a psychiatric disorder such as schizophrenia, bipolar disorder or major depression according to the criteria of the most current version of the Diagnostic and Statistical Manual of Mental Disorders (DSM). Mild depression or history of depression that is stable on treatment with a selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI) medication at a stable dose is acceptable.
Has non-AD dementia, such as vascular dementia, Lewy body dementia, frontotemporal disease, Parkinson disease dementia, B12 and thyroid deficiency caused dementia.
History of a seizure disorder, if stable on medication is acceptable.
Has a history or current evidence of long QT syndrome, Fridericia's formula corrected QT (QTcF) interval ≥ 450 ms for men and 460 ms for women, or torsades de pointes.
Has bradycardia (<50 bpm) or tachycardia (>100 bpm) on the ECG at screening.
Has uncontrolled Type-1 or Type-2 diabetes. A subject with HbA1c levels up to 7.5% can be enrolled if the investigator believes the subject's diabetes is under control.
Has clinically significant renal (CKD-EPI with normal <60 mL/min/BSA (body surface area) or hepatic impairment (ALP > 2.0 ULN and/or total bilirubin > 2.0 ULN) .
Has any clinically significant abnormal laboratory values. Participants with liver function tests (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) greater than twice the upper limit of normal will be excluded.
Is at imminent risk of self-harm, based on clinical interview and responses on the C SSRS, or of harm to others in the opinion of the Investigators. Participants must be excluded if they report suicidal ideation with intent, with or without a plan or method (e. g. positive response to Items 4 or 5 in assessment of suicidal ideation on the C SSRS) in the past 2 months, or suicidal behavior in the past 6 months.
Has cancer or has had a malignant tumor within the past year, except participants who underwent potentially curative therapy with no evidence of recurrence. (Participants with stable untreated prostate cancer or skin cancers are not excluded).
Alcohol / Substance use disorder, moderate to severe, in the last 5 years according to the most current version DSM.
Participation in another clinical trial with an investigational agent and have taken at least one dose of study medication, unless unblinded on placebo, within 4 weeks prior to the start of screening, or five half-lives of the investigational drug, whichever is greater.
The end of a previous investigational trial is the date the last dose of an investigational agent was taken.
Participants with learning disability or developmental delay.
Participants whom the site PI deems to be otherwise ineligible.
Participants with a known allergy to the investigational drug or any of its components. Here are all the inactive ingredients of the investigational medicinal product:
Subject is currently pregnant, breast-feeding and/or lactating.
Subject is currently taking strong and moderate CYP3A4 inhibitors and/or inducers. (e.g., CYP3A4 inhibitors Itraconazole, Ketoconazole, Azamulin, Troleandomycin, Verapamil; CYP3A4 inducers Rifampicin)
Stamford, Connecticut 06824, United States