Efficacy and Safety Evaluation of Milsaperidone as Adjunctive Therapy in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Study
- Trial ID
- 2024-520333-68-00
- Protocol
- VP-VHX-896-3201
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the efficacy of milsaperidone as an adjunctive treatment to antidepressant therapy in patients with major depressive disorder, specifically measuring the change from baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale total score.
The secondary objectives include:
- Evaluation of efficacy through changes from baseline in the Clinical Global Impression of Severity and improvements in the Clinical Global Impression of Change.
- Assessment of safety and tolerability via spontaneous reporting of adverse events.
- Analysis of milsaperidone effect on serum urate levels, including changes from baseline and frequency of shifts above the upper limit of normal.
- Investigation of the interaction between milsaperidone and urate with genetic variants and demographic factors on serum urate concentrations.
Participants
This clinical trial involves 250 participants diagnosed with major depressive disorder. The study population includes both male and female patients. Eligible individuals must meet DSM-5-TR criteria for the condition, with the current major depressive episode having commenced between 8 weeks and 24 months prior to screening. Participants are required to exhibit a minimum Montgomery-Asberg Depression Rating Scale total score of 24 and a Clinical Global Impressions-Severity score of 4 or higher at screening and baseline. Additionally, a Quick Inventory of Depressive Symptomatology-Self Report-16 score of at least 14 is required. The population consists of patients demonstrating an inadequate response to existing antidepressant therapy, defined as less than 50% improvement while maintaining a minimum effective dose of a specified monotherapy for at least 6 weeks.
Plans and Procedures
This Phase III study is a randomized, double-blind, placebo-controlled multicenter trial designed to evaluate the efficacy and safety of milsaperidone as an adjunctive therapy for patients diagnosed with major depressive disorder. Participants are assigned to receive either a 12 mg tablet of milsaperidone or an identical placebo administered via oral use. The primary objective is to assess the change from baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score. The research methodology involves a screening visit to confirm eligibility based on clinical criteria, followed by a baseline assessment. The study period focuses on the efficacy of the intervention through a 6-week treatment phase. Information regarding specific conditions for early termination or follow-up visit durations beyond the primary endpoint assessment is not provided.
Treatment
Milsaperidone, the experimental medication, is administered as a 12 mg tablet via the oral route. The active substance is (1S)-1-[4-[3-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propoxy]-3-methoxyphenyl]ethanol.
The control group receives a placebo, which is manufactured to be identical in size and appearance to the active treatment and is administered orally.
Efficacy
The efficacy of milsaperidone as an adjunctive therapy for major depressive disorder is evaluated by assessing the change from baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Meets DSM-5-TR criteria for MDD as confirmed by the Investigator and/or Sponsor-approved interviewer/rater via both: the Structural Clinical Interview for DSM-5, Clinical Trials Version (SCID-5-CT), updated for DSM-5-TR, and review of the patient’s medical records/history (a phone call with the patient’s physician may be acceptable in lieu of medical records), or, if lacking adequate records, written approval from the Sponsor or Sponsor’s Designee;
- The start of the current major depressive episode (MDE) is at least 8 weeks but no more than 24 months prior to screening;
- Rater-administered MADRS total score ≥ 24 at Screening and at Baseline;
- CGI-S – Severity of Illness score of ≥ 4 at Screening and Baseline;
- Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) score ≥ 14 at Screening and at Baseline;
- Currently having an inadequate response to antidepressant therapy (less than 50% improvement), as confirmed by the Investigator using the Antidepressant Treatment Response Questionnaire (ATRQ) and taking at least the minimum effective dose (per package insert) of one of the following antidepressants as monotherapy treatment for at least 6 weeks duration prior to the Screening Visit: bupropion, citalopram, duloxetine, escitalopram, fluoxetine, levomilnacipran (if locally approved for MDD), milnacipran (if locally approved for MDD), paroxetine, sertraline, venlafaxine, desvenlafaxine, vilazodone, vortioxetine
Exclusion Criteria
- Within the patient's lifetime, has a confirmed DSM-5-TR psychiatric diagnosis other than MDD, including: Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder or other psychotic disorder; Bipolar Disorder;
- Diagnosis of any current (within 6 months) psychiatric diagnosis other than MDD that has been confirmed by DSM-5-TR including: Anxiety disorders such as Panic Disorder or Generalized Anxiety Disorder; Obsessive-compulsive Disorder; Posttraumatic Stress Disorder. Note: Anxiety symptoms may be allowed if secondary to MDD, provided these symptoms do not require concurrent treatment; Patients with history of GAD documented on their MR may be included if the Investigator provides sufficient evidence that the diagnosis is no longer applicable. Eating disorder; Personality disorder of sufficient severity to have a major impact on the patient's psychiatric status;
- Experiences a ≥ 25% decrease in the MADRS total score between Screening and Baseline;
- Experiences a ≥ 25% decrease in the QIDS-SR-16 total score between Screening and Baseline;
- In the opinion of the Investigator, has a significant risk for suicidal behavior during participation in the study or is considered to be in imminent danger to themselves or others. Any of the following categorically exclude a patient from participation: at Screening, the patient scores "yes" on Suicidal Ideation Items 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within 6 months prior to Screening, or at Baseline, the patient scores "yes" on Suicidal Ideation Items 4 or 5 since the Screening Visit; at Screening, the patient has had 1 or more suicide attempts within 2 years prior to Screening; or at Screening or Baseline, the patient scores ≥ 5 on MADRS Item 10 (Suicidal Thoughts).
- Has a first MDE at age 60 years or older.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Recruiting | 17 May 2025 | 100 |
 Czechia | Recruiting | 17 May 2025 | 100 |
 Germany | Not Yet Recruiting | 17 May 2025 | 35 |
 Poland | Recruiting | 17 May 2025 | 100 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Milsaperidone | Test | TABLET | ORAL USE | 12 | 58 | PRD11920972 |
Placebo will be provided in size and appearance identical to those containing milsaperidone and will be administered orally. | Placebo | N/A | — | — | — | N/A |
Milsaperidone | Test | TABLET | ORAL USE | 12 | 58 | PRD12154591 |
Milsaperidone | Test | TABLET | ORAL USE | 12 | 58 | PRD12153485 |