To Evaluate the Efficacy, Safety, and Tolerability of Dronabinol Oral Solution for Agitation in Patients With Alzheimer's Disease
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.
detailed description
This is a randomised, double-blind, placebo-controlled study conducted in patients with a diagnosis of AD. The study consists of a screening period of up to 28 days (4 weeks), a 2-week titration period, during which the dose of dronabinol is gradually increased to the target maintenance dose. This is followed by a 10-week maintenance period (Weeks 3 through 12), where the target dose is maintained.
Following the 10-week maintenance period, eligible participants who complete the double-blind treatment period may enter a 6-month (24-week) open-label extension (OLE) to assess long-term safety and tolerability of dronabinol oral solution. Participants originally randomised to active treatment will continue receiving their established dose (2.5 mg, 5 mg, or 9.0 mg/day) without interruption. Participants originally randomised to placebo will undergo a 2-week titration period (Weeks 13 to 14) following the same dose escalation schedule as the main study to reach their target maintenance dose. All participants will receive open label dronabinol during the OLE period (Weeks 15 to 38). A final safety follow-up assessment will be conducted at Week 42 (4 weeks after the last dose of study medication). Standard of care medication will be maintained throughout this study for all participants as per the inclusion/exclusion criteria.
Titration/Transition Schedule:
Week 1/35: The starting dose will be 2.5 mg dronabinol once a day (QD) Week 2/14: Dronabinol dose will be increased to 2.5 mg twice a day (BID) for a total daily dose of 5 mg/day. Optional up-titration (Week 3/15 onwards, if tolerated) to 4.5 mg BID (total daily dose 9.0 mg/day).
Note: maximum dose in this study is 4.5 mg BID.
Dose escalation should occur only when a participant demonstrates BOTH:
Optimal safety profile:
Participant has completed ≥7 consecutive days at 5 mg/day without any clinically significant AE or group of AEs that singularly or in aggregate suggests to the Investigator or Sponsor that the study intervention is poorly tolerated and further treatment per protocol may not be safe (i.e., Grade 3 or above clinically significant AE deemed related to study intervention occurring in at least 2 study participants).
Suboptimal efficacy profile: Minimal or inadequate therapeutic response, defined by specific quantitative thresholds on validated agitation scales
official title
A Phase 2/3, Multicentre, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Dronabinol Oral Solution for Agitation in Patients With Alzheimer's Disease