Open-Label Long-Term Safety and Tolerability of ML-007C-MA (fesoterodine) in Adults with Hallucinations and Delusions of Alzheimer’s Disease Psychosis

Primary objective: to evaluate the ML-007C-MA safety and tolerability when administered long‑term to adults experiencing hallucinations and delusions associated with Alzheimer’s disease psychosis, providing essential data on the adverse event profile for chronic therapy in this population. Secondary objectives: • safety – ongoing assessment of adverse events and tolerability; • effectiveness – measurement of changes in hallucinations and delusions, clinical global impression of severity, agitation, cognition, and activities of daily living; • caregiver impact – evaluation of long‑term treatment effects on caregiver burden; • pharmacokinetics – characterization of the pharmacokinetic parameters of the investigational product in this patient group.

The trial enrolled 136 participants diagnosed with Hallucinations and Delusions Associated with Alzheimer’s Disease Psychosis, encompassing both male and female adults across two predefined age categories. All subjects had previously completed the double‑blind treatment phase of an antecedent study involving ML-007C-MA and were judged by investigators to potentially benefit from long‑term open‑label therapy. Enrollment required the ability to provide informed consent (or appropriate surrogate consent), the presence of a designated study care partner capable of reliable symptom reporting and study visit accompaniment, sufficient verbal communication ability (with corrective aids permitted), and residence in a stable living environment expected to be maintained throughout the study. Participants were required to adhere to contraception guidelines where applicable and could use wheelchairs or other ambulatory assistive devices. The population was therefore composed of patients with Alzheimer’s disease‑related psychosis who were medically stable, able to attend scheduled clinic visits, and supported by a consistent caregiving context.

The study is a Phase 4, open‑label, single‑arm investigation evaluating the long‑term safety and tolerability of ML‑007C‑MA in adults with hallucinations and delusions associated with Alzheimer’s disease psychosis. After an initial screening visit to confirm eligibility, participants who have completed the double‑blind treatment period of the antecedent trial enter an open‑label baseline visit where the 210 mg oral tablet of ML‑007C‑MA is dispensed and baseline safety assessments are recorded. Subsequent clinic visits occur at regular intervals (e.g., monthly for the first six months, then quarterly) to monitor treatment‑emergent adverse events, vital signs, laboratory parameters, electrocardiograms, and cognitive and behavioral scales; the primary endpoint is the incidence of treatment‑emergent adverse events leading to discontinuation. The trial continues for up to 22 months, with the final end‑of‑study visit documenting overall safety, efficacy measures, and pharmacokinetic sampling. Participants may be withdrawn prematurely for reasons such as serious adverse events, non‑compliance with dosing or visit schedule, withdrawal of consent, or a change in clinical status that precludes continued participation. The overall study duration spans from the projected recruitment start on 4 May 2026 to the anticipated completion date of 28 February 2028.

The investigational medication is fesoterodine, chemically identified as 5-[(1R,5R)-3-azabicyclo[3.1.0]hexan-1-yl]-3-methyl-1,2,4-oxadiazole, supplied in tablet form containing 210 mg of active substance. It is administered orally in accordance with the study’s dosing schedule for participants with hallucinations and delusions associated with Alzheimer’s disease psychosis. No additional non‑experimental treatments are specified in the protocol.

The efficacy of ML‑007C‑MA will be evaluated by assessing changes from the open‑label baseline in several clinical endpoints. The primary efficacy parameters include the NPI‑C H+D score (Neuropsychiatric Inventory‑Clinician version hallucinations and delusions subscale), the CGI‑S hallucinations and delusions domain‑specific score, the ADCS‑ADL total score, and the ZBI‑12 score. In participants with a baseline CGI‑S agitation and aggression domain score ≥ 4, the NPI‑C A+A score will also be evaluated.

These assessments will be performed using the respective validated instruments at each scheduled study visit throughout the treatment period. Scores will be recorded, and the magnitude of change from baseline will be analyzed using appropriate statistical methods for repeated measures, focusing on mean change, confidence intervals, and significance testing to determine treatment effect.