111. Efficacy and Safety of MIN-101: A New Drug for the Treatment of Negative Symptoms in Schizophrenia. A 12-Week Randomized, Double-Blind, Placebo-Controlled Trial
Bibliographic record
Abstract
Background: To compare the efficacy, safety, and tolerability of MIN-101, a compound with high affinities for sigma 2 and 5-HT2A receptors, to placebo in treating negative symptoms, in stabilized patients with schizophrenia. Methods: This multi-national Phase 2b trial enrolled 244 patients diagnosed with schizophrenia who were symptomatically stable for ≥3 months prior to entering the trial and had scores ≥20 on the three factors negative subscale of the Positive and Negative Syndrome Scale (PANSS). Patients were randomized to monotherapy with MIN 101 32 mg/day, MIN-101 64 mg/day or placebo in a 1:1:1 ratio. The primary endpoint was the PANSS negative symptom score based on the five factors (pentagonal) model. Secondary outcomes were the three factors PANSS negative symptom subscale score, the PANSS total score, the PANSS positive symptom score, the Clinical Global Impression (CGI), the Brief Negative Symptoms Scale (BNSS), the Brief Assessment of Cognition in Schizophrenia (BACS), the Calgary Depression Scale for Schizophrenia (CDSS), and the Personal and Social Performance (PSP) scale. Safety parameters included treatment-emergent adverse events (TEAE), clinical laboratory, vital signs, electrocardiograms, Sheehan-suicidality tracking scale (S-STS), and the Abnormal Involuntary Movement Scale (AIMS). The Mixed-Effect Model Repeated Measure (MMRM) was used for analyzing the efficacy data. Results: The three treatment groups were balanced on all demographic and illness-related baseline characteristics. Statistically significant reduction in the primary endpoint score was demonstrated for MIN-101 32 mg and 64 mg compared to placebo (P ≤ .022, ES 0.45 and ≤ .003, ES 0.58, respectively). This was supported by similar effects on most of the secondary measurements including: the PANSS three factors negative symptoms subscale, PANSS total score, CGI, BACS, CDSS, and PSP. There were no statistically significant differences in PANSS positive subscale scores between MIN 101 and placebo. No weight gain or clinically significant changes in vital sings, prolactin levels, routine laboratory values, metabolic indices and extrapyramidal symptom scores (EPS) were observed. One patient on 64 mg MIN-101 was discontinued from the trial based on a-priori established QT interval prolongation criteria and a second one following an episode of syncope. Conclusion: MIN-101 at dosages of 32 and 64 mg/day demonstrated statistically significant efficacy of medium ES in reducing negative symptoms and good tolerability in stable schizophrenia patients. Since positive symptoms and EPS did not change, the improvement in negative symptoms was not secondary to improvement in positive symptoms or EPS, suggesting that MIN-101 might be the first specific treatment to have a direct effect on negative symptoms.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".