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Phase I, single-dose study to compare pharmacokinetics of depemokimab delivered by safety syringe device or autoinjector in healthy adults

2024· article· en· W4404096841 on OpenAlexaff
Stein Schalkwijk, Jee Sun Min, Chiara Zecchin, Brian Spears

Bibliographic record

Venuenot available
Typearticle
Languageen
FieldMedicine
TopicPharmaceutical studies and practices
Canadian institutionsInternational Development Research Centre
Fundersnot available
KeywordsSyringePharmacokineticsMedicinePharmacology

Abstract

fetched live from OpenAlex

Background: Depemokimab is the first and only humanised anti-IL-5 antibody with enhanced binding affinity and high potency, resulting in an extended half-life, enabling 6-monthly dosing and sustained inhibition of broad inflammatory function. Aim: Compare pharmacokinetics (PK), immunogenicity and safety of depemokimab administered by safety syringe device (SSD) or autoinjector (AI). Methods: Participants randomised (1:1) received single-dose depemokimab 100 mg subcutaneously via SSD or AI, in the upper arm, abdomen or thigh (randomised 1:1:1). PK parameters were assessed up to Day 183 post dose and relative bioavailability calculated by AI:SSD geometric mean ratio (GMR). Immunogenicity (presence of anti-drug antibodies) and adverse events (AEs) were also assessed. Results: Each arm included 70 participants. PK was similar between devices. AI:SSD adjusted GMR and 90% CIs were within the bioequivalence range of 0.8 to 1.25 for Cmax (1.03 [0.96, 1.09]) and AUC(0-inf) (1.03 [0.96, 1.10]). When pooled across devices, depemokimab geometric mean (log SD) Cmax (µg/mL) and AUC0-inf (µg*day/mL) was 14.1 (0.25) and 1004.4 (0.30) for upper arm, 15.3 (0.22) and 1119.3 (0.22) for abdomen and 15.2 (0.23) and 1091.0 (0.28) for thigh, respectively. Immunogenicity incidence was low (1%) for both devices. Drug-related AE incidence was 19% (SSD) and 20% (AI). Conclusions: For single-dose depemokimab, PK and bioavailability were similar for SSD and AI; criteria for bioequivalence were met. PK was generally comparable across injection sites. Incidence of immunogenicity and AEs were low and similar for SSD and AI. Funding: GSK (214099, NCT05602025 )

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Non-randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.007
Threshold uncertainty score0.024

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0070.001

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.

Opus teacher head0.101
GPT teacher head0.444
Teacher spread0.344 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNon-randomized trial
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".

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Citations0
Published2024
Admission routes1
Has abstractyes

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