To Evaluate the Efficacy, Safety, and Tolerability of Dronabinol Oral Solution for Agitation in Patients With Alzheimer's Disease

NCT07422311 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: BEN-DRO-ADA
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

This study tests a medication called dronabinol in people with Alzheimer's disease. First, participants go through up to 4 weeks of screening. Then, over 2 weeks, the dose of the study drug is slowly increased. For the next 10 weeks, participants stay on either dronabinol or a placebo. After finishing this part of the study, participants can join a 6-month extension where everyone receives dronabinol. Those already on the drug stay on their same dose, while those who were on placebo gradually increase their dose over 2 weeks. All participants take dronabinol for the rest of the extension, then complete a final safety check 4 weeks after stopping the medication. Usual medical treatments are continued throughout the study.

Conditions

Agitation in Dementia

Outcome Measures

Primary Outcomes (2)

• To assess the efficacy of dronabinol oral solution compared to placebo in reducing agitation in patients with AD.

  Agitation response is no greater than a partial response (i.e., Cohen-Mansfield Agitation Inventory \[CMAI\] 4-7 points improvement;

  12 weeks

• Change from baseline to Week 12 in the CMAI total score, comparing Dronabinol oral solution versus placebo

  Neuropsychiatric Inventory-Clinician \[NPI-C\] Agitation/Aggression domain 3-5 points improvement).

  12 weeks

Study Arms (2)

Participants will receive Dronabinol oral solution

EXPERIMENTAL

Dronabinol oral solution (target n=70)

Drug: Dronabinol Oral Solution

Participants will receive Placebo

PLACEBO COMPARATOR

Control arm: Matching placebo (target n=70)

Other: Placebo Control

Interventions

Dronabinol Oral Solution DRUG

Dronabinol Oral Solution for Agitation in Patients with Alzheimer's Disease

Participants will receive Dronabinol oral solution

Placebo Control OTHER

Placebo (no THC)

Participants will receive Placebo

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Participant or legal representative is willing and capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form and is willing and able to return for all study visits and comply with all protocol requirements and procedures.
• \. Adult males and females, 50 to 90 years of age (inclusive) at screening.
• \. Participants must have a diagnosis of dementia due to AD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and a diagnosis of probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA).
• \. Presence of Agit-AD as defined by the provisional criteria from the International Psychogeriatric Association (IPA). The definition requires the presence of cognitive impairment, evidence of emotional distress, one of three observable types of behaviour (excessive motor activity, verbal aggression, physical aggression), requires that the behaviour cause excess disability, and notes that the behaviours cannot be solely attributable to another disorder such as psychiatric illness, medical illness, or effects of substance use.
• \. Clinically significant severity of agitation defined by NPI-C Agitation or NPI-C Aggression \>4.
• \. Mini Mental Status Examination (MMSE) score of 8-20 (inclusive).
• \. Cohen-Mansfield Agitation Inventory (CMAI) total score ≥60 at both Screening and Baseline visits, with at least one item in the aggressive behaviour domain (Factor 1) scored \>3 (occurring ≥ once or twice per week). Alternatively, meet Factor 1 positivity criterion: one or more aggressive behaviours occurring several times per week, OR two or more occurring once or twice per week, OR three or more occurring less than once per week.
• \. If a participant is receiving AD-specific treatment, they must have been on a stable dose for \>3 months prior to first dose of study drug.
• \. Participant must have at least 1 study partner (e.g., spouse or caregiver in close contact) to support participant in all scheduled study visits and procedures.
• \. Participants who do not live in assisted living facilities are eligible to participate and must be capable of returning for study visits.
• \. Adequate vision and hearing (with corrective devices if needed) to complete study assessments, as judged by the investigator. Participants must be able to:
• Read and understand consent documents and questionnaires
• Hear and respond to verbal instructions for cognitive testing
• Participate in clinical interviews
• \. Has adequate hematologic and organ function, as indicated by the following laboratory values, prior to Cycle 1 Day 1:

You may not qualify if:

• \. Known hypersensitivity to the study drug or any of the study drug ingredients.
• \. History of anaphylaxis or other significant allergy which, in the opinion of the PI (or delegate), would interfere with the volunteer's ability to participate in the study.
• \. History or presence of clinically significant, unstable (not well controlled on medications) cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, psychiatric, or neurological disease/disorder, within the past 3 months determined by the PI (or delegate) to be clinically relevant.
• \. History of recurrent falls (≥2 falls within 6 months prior to Screening) resulting in injury or associated with acute illness, loss of consciousness, or abnormal vital signs, history of fall with fracture within 12 months of Screening.
• \. History of surgery or hospitalisation within 3 months prior to screening, or surgery planned during the study.
• \. Any history of malignant disease in the last 5 years (excludes surgically resected skin squamous cell or basal cell carcinoma).
• \. History of clinically significant CNS event and/or diagnosis in the past 5 years, including but not limited to epilepsy, significant CNS trauma, CNS surgery, neurosyphilis, meningitis, encephalitis or meningoencephalitis.
• \. Baseline delirium as determined by Confusion Assessment Method (CAM) and Diagnostic and Statistical Manual of Mental Disorders (DSM) - criteria.
• \. Commencement of medications that affect the CNS within \<4 weeks prior to first dose of study drug, including but not limited to cannabinoid, benzodiazepines, anti-depressant, and antipsychotic medications.
• \. History of major psychiatric disorder(s) in the past 5 years, including but not limited to psychosis and bipolar disorder. Mild psychiatric disorder(s) that is well controlled and stable on medication therapy for \>1 year that is not prohibited on this study may be allowed on a case-by-case basis in discussion with study sponsor, if deemed unlikely to put participant at a higher risk of treatment-related toxicity and/or interfere with the integrity of study outcome.
• \. A history of or positive test results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit. A negative HCV RNA result is acceptable for enrolment.
• \. Medications with significant drug-drug interaction potential:
• Strong CYP3A4 or CYP2C9 inhibitors (e.g., ketoconazole, ritonavir, fluconazole, amiodarone) within 2 weeks of Screening or anticipated need during study
• disulfiram/metronidazole (risk due to alcohol content)
• \. Positive drugs of abuse test (for a list of drugs tested refer to Section 11.1.8), cotinine test, or alcohol breath test results at screening and prior to dosing on Day 1.

Sponsors & Collaborators

• Benuvia Therapeutics Inc.: lead
• Mandara: collaborator

Study Sites (1)

Finders Medical Center

Bedford Park, SA Adelaide, 5042, Australia

Location

MeSH Terms

Conditions

Aberrant Motor Behavior in Dementia

Interventions

Dronabinol

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Lauren Priest, MD

  Division of Rehabilitation, Aged Care and Palliative Care Flinders Medical Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aimee Cayzer

CONTACT

0482 130 622; rapmtu@sa.gov.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: yes, sponsor, clinical and regulatory affairs staff
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a randomized, Double-Blind, Placebo-Controlled Study where participants will be divided in two group. One group will received the drug and the other will receive the placebo.

Study Record Dates

• First Submitted: February 11, 2026
• First Posted: February 20, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 30, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)