IGC-AD1 Trial on Agitation in Dementia Due to Alzheimer's

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy of an oral medication, IGC-AD1 that is a natural THC-based (Tetrahydrocannabinol) formulation, administered in micro doses, twice a day, on symptomatological Agitation, in patients with mild to severe dementia from Alzheimer's.

Detailed Description
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This is a placebo-controlled, multi-site, parallel, double blind, randomized study. Enrollment is open for Participants ages 60 and above with mild to severe dementia due to Alzheimer's Disease, with established symptomatological Agitation, for a minimum of two weeks prior to enrollment, with Agitation due to other etiologies, or recent, or transient Agitation symptoms ruled out. Clinical Agitation is established with a baseline NPI-12 (Agitation Domain only) score ≥ 4 as well as meeting the IPA criteria for Agitation. The medication is titrated to BID over two days and down over two days at End of Trial (EOT). Caregivers will monitor and record in a logbook vitals daily using Sponsor provided scales and logbook. Safety will be monitored with daily calls to the Participant/Caregiver dyad for the first four days followed by calls every third day till EOT. Week two is an on-site visit with week-four being optional. Both solicited AEs and non-solicited AEs will be monitored, assessed, graded, and tabulated. Solicited AEs include the following: somnolence, falls, dizziness, asthenia, nausea, suicidal ideation, tachycardia, bradycardia, hypertension and hypotension, and BMI. The primary objective of the study is to assess the efficacy of IGC-AD1 on Agitation as scored by the CMAI between baseline and EOT with the secondary objective being acute efficacy as measured by the CMAI between baseline and week two. There are several exploratory objectives included elsewhere. The trial will also have blood draws for sparse Pharmacokinetics (PK).

Official Title
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A Phase 2, Multicenter, Double-Blind, Randomized, Placebo-Controlled, Trial of the Safety and Efficacy of IGC-AD1 on Agitation in Participants With Dementia Due to Alzheimer's Disease

Conditions
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NPS, Alzheimer Disease, Agitation,Psychomotor, Depression, Anxiety, Memory Impairment, Care Giving Burden, Agitated; State, Acute Reaction to Stress, Aggression, Aggressive Outburst

Intervention / Treatment
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* Drug: Agitation management in Alzheimer's disease (IGC-AD1-Active)
* Drug: Agitation management in Alzheimer's disease (IGC-AD1-Placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be eligible to participate in this study, an individual must meet all the following criteria: Participant and/or Caregiver must provide a signed and dated Informed Consent Form (ICF) prior to any study procedures. Must have a Caregiver who is able and willing to comply with all required study procedures. The Caregiver must be known to the Participant and must be able to use electronic devices such as a cell phone, video conference over a laptop or cell phone, weighing scale, and be able to learn to take blood pressure, among others. Based on local practice, Participants that cannot consent may have Caregiver's consent provided by the Caregiver as, among others a) Power of Attorney, or b) is a spouse, or c) a sibling or d) a child or e) a close relation. The practice of accepting consent must be consistent with established practice at the site and jurisdiction. Participants must consent to CYP450 and apolipoprotein E (ApoE) genotyping, Pharmacokinetics and storage of blood samples for future genetic testing. Diagnosis of Alzheimer's by National Institute on Aging and Alzheimer's Association (NIA-AA) criteria. Clinically significant Agitation assessed by: Neuropsychiatric Inventory (NPI (Agitation) ≥ 4. The presence of clinically significant, persistent Agitation based on the International Psychogeriatric Association (IPA) definition rather than those with recent onset and occasional symptoms, and Agitation not attributable to another psychiatric disorder, suboptimal care conditions, other underlining medical condition, or the physiological effects of a substance. Negative drug screen, except for benzodiazepines if Participant has been using them in stable doses for at least 3 months before screening. All medications used for behavioral symptoms should be in stable doses for at least 3 months before screening. Women must be of no childbearing potential (postmenopausal, defined as cessation of menses for at least 12 months, without an alternative medical cause for amenorrhea) or surgically sterile (hysterectomy, bilateral oophorectomy, or bilateral tubal ligation)). Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation in this study: Prior adverse reaction to cannabinoids or to any component of study drug (IGC-AD1 and placebo): Tetrahydrocannabinol (THC), melatonin, honey, curcumin, ethyl alcohol, vitamin-E tocopheryl polyethylene glycol succinate (TPGS), ascorbic acid, water, tween-80, and rutin. Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic, hematologic disease, which might confound assessment of safety outcomes. History of seizures, schizophrenia, or bipolar disorder. Has participated in an investigational drug or device study within 30 days prior to study start. Urine drug screen positive for drug use, except for benzodiazepines if Participant was using them previously and their dose had remained stable for at least 3 months before screening. History of Alcohol and Drug use, excluding marijuana, within one year prior to enrollment. Hypertension: Participants with a history of uncontrolled hypertension as determined by the PI and Participants with a hypertensive crisis in the six months prior to enrollment. Falls: Participants with a history of recurrent falls defined as more than two falls in the six-month period prior to enrollment and a history of falls resulting in injuries or associated with a new acute illness, loss of consciousness, fever, or abnormal blood pressure (the definition of recurrent falls is taken from American Family Physician (AFP).

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multi-site, Randomized, double-blind, placebo-controlled parallel-group trial in adults with mild to severe dementia from Alzheimer's and symptomatological Agitation.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Comparator: IGC-AD1Active<br>IGC-AD1 Active Treatment THC plus another API plus excipients. | Drug: Agitation management in Alzheimer's disease (IGC-AD1-Active)<br>* A non-sterile solution for oral administration.<br>* Other names: IGC-AD1 Active;|
| Placebo Comparator: Placebo Comparator: IGC-AD1 Placebo<br>IGC-AD1 Placebo, similar to Active in color, taste, and texture, with excipients but without APIs. | Drug: Agitation management in Alzheimer's disease (IGC-AD1-Placebo)<br>* A non-sterile solution for oral administration similar in color and texture to the Active.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Agitation | Change in mean Cohen Mansfield Agitation Inventory (CMAI) score | Baseline to week six | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Agitation | Change in mean Cohen Mansfield Agitation Inventory (CMAI) score | Baseline to week two | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cannabis, Tetrahydrocannabinol, THC, Melatonin, Alzheimer's, Marijuana, Hemp, Agitation, Dementia, Depression, Anxiety, Memory, NPI, CMAI, Dronabinol