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Record W4387516303 · doi:10.1111/cts.13623

MIJ821 (onfasprodil) in healthy volunteers: First‐in‐human, randomized, placebo‐controlled study (single ascending dose and repeated intravenous dose)

2023· article· en· W4387516303 on OpenAlexaff
Baltazar Gomez‐Mancilla, Jeffrey A. Levy, Thomas Faller, Gil Issachar, Ziv Peremen, Offir Laufer, Revital Shani‐Hershkovich, Kostas Biliouris, Ela Walker, Mark P. Healy, Oleksandr Sverdlov, Sachin N. Desai, S. Nassir Ghaemi, Jang‐Ho Cha, Y. Gopi Shanker

Bibliographic record

VenueClinical and Translational Science · 2023
Typearticle
Languageen
FieldMedicine
TopicEpilepsy research and treatment
Canadian institutionsMcGill University
FundersNovartis Institutes for BioMedical Research
KeywordsMedicinePlaceboPharmacokineticsTolerabilityAdverse effectAnesthesiaSingle CenterIntravenous InfusionsInternal medicine

Abstract

fetched live from OpenAlex

Abstract This single‐center study administered MIJ821 (onfasprodil) as an intravenous infusion to healthy volunteers and included two parts: a single ascending dose study (Part 1) and a repeated intravenous dose study (Part 2). Primary objective was to evaluate the safety and tolerability of single ascending intravenous doses infused over a 40‐min period and of two repeated doses (1 week apart) of MIJ821 in healthy volunteers. Secondary objectives were to assess the pharmacokinetics of MIJ821 after intravenous infusion in Part 1 and Part 2 of the study. Overall, 43 subjects in Part 1 and 12 subjects in Part 2 were randomized in the study. Median age in Part 1 and Part 2 was 45.0 and 43.5 years, respectively, with the majority being Caucasian (Part 1: 84%; Part 2: 92%). 19 subjects (44.2%) in Part 1 and 8 subjects (66.7%) in Part 2 experienced at least one adverse event (AE). Following single dose in Part 1 and Part 2, the AUC inf values of MIJ821 increased in a dose‐proportional manner across the dose range 0.016–0.48 mg/kg and the C max values in a slight overproportional manner across the dose range 0.048–0.48 mg/kg. At the highest dose of 0.48 mg/kg, the geometric mean AUC inf was 708 h ng/mL and the geometric mean C max was 462 ng/mL. Inspection of 1‐h post‐dose resting electroencephalography activity across cohorts showed a relationship to administered dose, providing exploratory evidence of distal target engagement. In conclusion, MIJ821 showed a good safety and tolerability profile in healthy volunteers. Dissociative AEs were mild, transient, and dose‐dependent.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.006
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.160
Threshold uncertainty score0.419

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0060.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.075
GPT teacher head0.408
Teacher spread0.334 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations10
Published2023
Admission routes1
Has abstractyes

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