LY03020 (also known as LPM787000048 Maleate Extended-Release) is an investigational drug being developed by Luye Pharma Group Ltd. for the treatment of Alzheimer's disease psychosis and schizophrenia. This Phase 1 clinical trial (NCT07230652) evaluates the safety, tolerability, and pharmacokinetics of multiple oral doses of LY03020 extended-release tablets in Chinese adult healthy subjects and subjects with stable schizophrenia.
| Field |
Value |
| NCT ID |
NCT07230652 |
| Status |
Recruiting |
| Phase |
Phase 1 |
| Sponsor |
Luye Pharma Group Ltd. |
| Intervention |
LY03020 (LPM787000048 Maleate Extended-Release Tablets) |
| Enrollment |
40 participants |
| Duration |
7 days dosing + 4 days follow-up |
| Location |
Beijing, China |
This is a randomized, double-blind, placebo-controlled, dose-escalating Phase 1 clinical study with the following design characteristics:
- Allocation: Randomized
- Intervention Model: Parallel Assignment
- Purpose: Treatment
- Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
| Arm |
Description |
| LY03020 |
Experimental - Subjects will take LY03020 from Day 1 to Day 7 |
| Placebo |
Comparator - Subjects will take matching placebo from Day 1 to Day 7 |
- Voluntary informed consent
- Male or female aged 18 to 45 years
- Body weight ≥50.0 kg (male) / ≥45.0 kg (female)
- BMI between 18.5 and 26.0 kg/m²
- Voluntary informed consent (subject and/or guardian)
- Male or female aged 18 to 60 years
- Body weight ≥50.0 kg (male) / ≥45.0 kg (female)
- BMI between 18.5 and 32.0 kg/m²
- DSM-V criteria for primary diagnosis of schizophrenia
- PANSS total score ≤80 and CGI-S score ≤4 at screening
- Stable condition for 1 month before consent to baseline
- Clinically significant medical condition or chronic disease
- Nonprescription drugs within 7 days or prescription drugs within 28 days prior to administration
- History of keratopathy, fundus disease, increased intraocular pressure, or angle-closure glaucoma
- History of orthostatic hypotension or syncope
- Clinically significant abnormal vital signs, laboratory values, or ECGs
- Positive test for HBsAg, HCV-Ab, HIV-Ab, or syphilis antibody
- Other mental disorders except schizophrenia within 6 months (DSM-5)
- Treatment-resistant schizophrenia
- Neuroleptic malignant syndrome (NMS) history
- Anticipated need for antipsychotic regimen modifications
- Suicide attempts or suicidal ideation within past 6 months (C-SSRS questions 4 or 5)
- MAOI within 28 days or dietary supplements/TCM within 7 days
- HbA1c ≥7%
- Congenital long QT syndrome
- Uncontrolled cardiovascular disease (NYHA class II+ CHF, unstable angina, MI within 6 months)
- Resting heart rate <50 bpm
- QTc >450 ms (male) / >460 ms (female)
- Number of participants with adverse events (AEs) and serious adverse events (SAEs)
- Time Frame: Up to Day 11
- Clinical laboratory assessment abnormalities
- Change in PANSS (Positive and Negative Syndrome Scale) at Day 11
- C-SSRS (Columbia-Suicide Severity Rating Scale) changes
- Barnes Akathisia Rating Scale (BARS) changes
- Simpson-Angus Scale (SAS) changes
- Cmax,ss (Maximum observed concentration at steady state)
- Cmin,ss (Minimum observed concentration at steady state)
- AUC0-τ,ss (Area under concentration-time curve during dosing interval)
- AUC0-∞,ss (AUC from time zero to infinity at steady state)
- Tmax,ss (Time to maximum observed concentration)
- t1/2 (Apparent terminal elimination half-life)
- Ra(AUC) and Ra(Cmax) accumulation ratios
- Vital sign abnormalities
- 12-lead ECG abnormalities
- Ophthalmic examination abnormalities
While the specific mechanism of action for LY03020 has not been publicly disclosed, the trial includes subjects with Alzheimer's disease psychosis and schizophrenia, suggesting the compound may target:
- Dopaminergic signaling: Given the PANSS assessment and schizophrenia indication
- Serotonergic pathways: Often implicated in psychosis treatment
- Glutamatergic modulation: NMDA receptor modulation in psychosis
- Cognitive enhancement: Relevant to Alzheimer's disease psychosis
| Compound |
Target |
Indication |
Phase |
| LY03020 |
Unknown (under investigation) |
AD psychosis, schizophrenia |
Phase 1 |
| Pimavanserine |
Inverse agonist at 5-HT2A/C |
AD psychosis, schizophrenia |
Phase 3 |
| Brexpiprazole |
Partial agonist at 5-HT1A/D2 |
Schizophrenia, AD agitation |
Approved |
| Cariprazine |
D3/D2 partial agonist |
Schizophrenia, bipolar |
Approved |
| Nuplazid |
Inverse agonist at 5-HT2A |
帕金森病 psychosis |
Approved |
Alzheimer's disease psychosis (ADP) affects up to 50% of AD patients and is characterized by:
- Visual and auditory hallucinations
- Delusions and paranoid ideations
- Behavioral disturbances
- Often indicates more rapid disease progression
Treatment Approaches:
- Atypical antipsychotics (off-label, limited efficacy)
- Pimavanserin (FDA approved for PDP)
- Non-pharmacological interventions
- Novel agents in development (like LY03020)