A Phase 2 Randomized Trial of NBI-1065846 (TAK-041) in Patients With Anhedonia Associated With Major Depressive Disorder
Bibliographic record
Abstract
BACKGROUND: Anhedonia is a core symptom of major depressive disorder (MDD) that may result from aberrant lateral habenula hyperactivity. Targeting G-protein coupled receptor 139 (GPR139) may improve anhedonia by modulating lateral habenula activity. NBI-1065846 is an investigational GPR139 agonist that improved anhedonia, anxiety, and depression in rodent models. METHODS: TERPSIS was a phase 2, proof-of-concept clinical study. Adults with MDD experiencing a major depressive episode with anhedonia were randomized 1:1 to NBI-1065846 or placebo for 8 weeks. The primary endpoint was the change in the Dimensional Anhedonia Rating Scale (DARS) score. Secondary endpoints were change in total Montgomery Åsberg Depression Rating Scale (MADRS) score in participants with a baseline 17-item Hamilton Depression Rating Scale (HAM-D17) score of ≥19 (moderate to severe) and change in Clinical Global Impression of Severity (CGI-S) score. All changes were from baseline to Day 57. RESULTS: In total, 93 participants received study treatment (NBI-1065846, n = 46; placebo, n = 47). Both groups showed notable improvements in DARS scores from baseline to day 57 (least-squares mean change: NBI-1065846, 13.5; placebo, 17.4), with no statistically significant difference (NBI-1065846 vs. placebo, P = 0.8663). Similarly, MADRS ( P = 0.7008) and CGI-S ( P = 0.9051) scores showed no significant difference between groups. All treatment-emergent adverse events in the NBI-1065846 group were mild or moderate in severity. CONCLUSIONS: The TERPSIS study did not meet its primary or secondary endpoints. NBI-1065846 was generally well tolerated. Addressing the lack of treatment options for anhedonia remains an important unmet clinical need.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.009 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".